Drug eluting stents · Drug eluting stents A systematic review and meta-analysis of randomized...

Prepared by:

Michel Cucherat, MD, PhD

Faculte de medecine LaennecLyon, France

[email protected]

Drug eluting stents

A systematic review and meta-analysis of randomized clinical trials

2008 - 10 - 14

Prepared forHAS

Part or all of the information presented in this document may be unpublished material and should be treated asthe confidential property of HAS, not to be divulged to unauthorized persons, in any form, including

publications and presentations, without the written consent of HAS.

CONTENTS 3

Contents

I Unparticular patients 7

1 Overview of available evidence for unparticular patients 91.1 Main results for Unparticular patients . . . . . . . . . . . . . . . . . . . . . . . . 141.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 141.3 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 141.4 comparison versus sirolimus eluting stent - summary of results . . . . . . . . . . 15

2 Details for comparison versus bare-metal stent 292.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

3 Details for comparison versus paclitaxel eluting stent 533.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 533.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

4 Details for comparison versus sirolimus eluting stent 664.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 664.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

5 Ongoing studies of Unparticular patients 755.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

II Diabetic patients 77

6 Overview of available evidence for diabetic patients 796.1 Main results for Diabetic patients . . . . . . . . . . . . . . . . . . . . . . . . . . . 836.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 836.3 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 836.4 comparison versus rapamycin eluting stent - summary of results . . . . . . . . . 83



9 Details for comparison versus rapamycin eluting stent 1109.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1109.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112

10 Ongoing studies of Diabetic patients 11310.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113

4 CONTENTS

III Acute myocardial infarction 115

11 Overview of available evidence for acute myocardial infarction 11711.1 Main results for Acute myocardial infarction . . . . . . . . . . . . . . . . . . . . . 12011.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 12011.3 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 120



14 Ongoing studies of Acute myocardial infarction 14714.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

IV Small vessels 149

15 Overview of available evidence for small vessels 15115.1 Main results for small vessels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15415.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 15415.3 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 154



18 Ongoing studies of small vessels 17318.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173

V Long or complex lesion 175

19 Overview of available evidence for long or complex lesion 17719.1 Main results for long or complex lesion . . . . . . . . . . . . . . . . . . . . . . . . 18119.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 18119.3 comparison versus CABG - summary of results . . . . . . . . . . . . . . . . . . . 18119.4 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 181


21 Details for comparison versus CABG 19721.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19721.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199

CONTENTS 5


23 Ongoing studies of long or complex lesion 21123.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211

VI In-stent restenosis 213

24 Overview of available evidence for in-stent restenosis 21524.1 Main results for in-stent restenosis . . . . . . . . . . . . . . . . . . . . . . . . . . 21924.2 comparison versus ballon angioplasty - summary of results . . . . . . . . . . . . 21924.3 comparison versus brachytherapy - summary of results . . . . . . . . . . . . . . 21924.4 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 219

25 Details for comparison versus ballon angioplasty 22525.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22525.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227

26 Details for comparison versus brachytherapy 23026.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23026.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232


28 Ongoing studies of in-stent restenosis 24128.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241

VII Bypass graft lesions 243

29 Overview of available evidence for bypass graft lesions 24529.1 Main results for bypass graft lesions . . . . . . . . . . . . . . . . . . . . . . . . . 24729.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 247


31 Ongoing studies of bypass graft lesions 25731.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257

VIII Unprotected left main coronary artery stenosis 259

32 Overview of available evidence for unprotected left main coronary arterystenosis 26132.1 Main results for unprotected left main coronary artery stenosis . . . . . . . . . . 26332.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 263

6 CONTENTS


34 Ongoing studies of unprotected left main coronary artery stenosis 27134.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271

IX Total occlusion 273

35 Overview of available evidence for total occlusion 27535.1 Main results for total occlusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27735.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 277


37 Ongoing studies of total occlusion 28737.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287

X Bifurcation 289

38 Overview of available evidence for bifurcation 29138.1 Main results for bifurcation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29338.2 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 293


40 Ongoing studies of bifurcation 29940.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299

Part I

Unparticular patients

7

9

1 Overview of available evidence for unparticular

patients

A total of 34 RCTs which randomized 19365 patients were identified. (see tables 1.1 to 1.3 )In all, 22 reports concerned comparison versus bare-metal stent , 10 the comparison versus

paclitaxel eluting stent and 2 the comparison versus sirolimus eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 2 (page 29)

for comparison versus bare-metal stent, in section 3 (page 53 ) for comparison versus paclitaxeleluting stent and in section 4 (page 66 ) for comparison versus sirolimus eluting stent.

The average study size was 605 patients per arm (range 15 to 1065 per arm). The first studywas published in 2002, and the last study was published in 2008. 10 trials were double blindand 14 were open-label in design. All included studies were reported in English language. Wefound one unpublished trial.

10CHAPTER 1. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPARTICULAR PATIENTS

Table

1.1

:M

ain

study

chara

cter

isti

cs-

Unpar

ticu

lar

pat

ients

-co

mpar

ison

vers

us

bare

-met

alst

ent

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

bare

-meta

lst

ent

Dactinom

ycin

elu

ting

stentvers

us

bare

-meta

lst

ent

AC

TIO

N,

2004

[1,

2]

Mult

ilin

kT

etra

sten

tvs.

unco

ate

dM

ult

ilin

kT

etra

sten

t

241

vs.

119

single

-blind

Para

llel

gro

ups

majo

radver

seca

rdia

cev

ents

at

30d

worl

dw

ide

Evero

lim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

SP

IRIT

III,

2008

[3,

4]

XIE

NC

EV

vs.

Taxus

669

vs.

333

single

-blind

Para

llel

gro

ups

in-s

egm

ent

late

loss

US

FU

TU

RE

II,

2006

[5,

6,

7]

unpublish

ed

CH

AM

PIO

Nvs.

bare

-met

al

sten

t43

vs.

21

double

-blind

Para

llel

gro

ups

angio

gra

phic

late

loss

at

6m

onth

sN

A

FU

TU

RE

I,2004

[8]

ever

olim

us

coate

dS-S

tent

vs.

S-S

tent

27

vs.

15

single

-blind

Para

llel

gro

ups

MA

CE

Ger

many

SP

IRIT

I,0

[9,

10,

11]

unpublish

ed

XIE

NC

Evs.

MU

LT

I-L

INK

VIS

ION

28

vs.

32

single

-blind

Para

llel

gro

ups

in-s

tent

late

loss

NA

SP

IRIT

II,

0[]

unpublish

edX

IEN

CE

Vvs.

TA

XU

SE

XP

RE

SS2

223

vs.

77

single

-blind

(pati

ent)

Para

llel

gro

ups

In-s

tent

late

loss

NA

Paclita

xelelu

ting

stentvers

us

bare

-meta

lst

ent

SC

OR

E,

2004

[12,

13]

QuaD

DS

sten

ts(p

acl

itaxel

)vs.

unco

ate

dco

ntr

ol

sten

ts

126

vs.

140

op

enP

ara

llel

gro

ups

none

Worl

dw

ide

TA

XU

SIV

,2004

[14]

TA

XU

Svs.

EX

PR

ESS

662

vs.

652

double

-blind

Para

llel

gro

ups

TV

RU

nit

edSta

tes

TA

XU

SI,

2003

[15]

TA

XU

SN

IRvs.

NIR

sten

t31

vs.

30

double

-blind

Para

llel

gro

ups

Com

bin

ati

on

of

dea

th,A

MI,

TV

R,

sten

tth

rom

bosi

s

Ger

many

TA

XU

SII

,2003

[16]

TA

XU

Svs.

NIR

sten

t266

vs.

270

double

-blind

Para

llel

gro

ups

Neo

inti

mal

pro

life

rati

on

Glo

bal

Paclita

xel,

non-p

oly

meri

celu

ting

stentvers

us

bare

-meta

lst

ent

cont

inue

d...

11

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gdesi

gn

Pri

mary

Endp

oin

tL

ocalisa

tion

DE

LIV

ER

,2004

[17,

18,

19]

non-p

oly

mer

-base

dpacl

itaxel

-coate

dA

CH

IEV

Est

ent

vs.

stain

less

stee

lM

ult

i-L

ink

(ML

)P

EN

TA

sten

t

524

vs.

519

single

-blind

Para

llel

gro

ups

targ

et-v

esse

lfa

ilure

US

EL

UT

ES,

2004

[20]

coate

dV

-Fle

xP

lus

vs.

V-F

lex

Plu

s152

vs.

38

op

enP

ara

llel

gro

ups

per

cent

dia

met

erst

enosi

sE

uro

pe

ASP

EC

T,

2003

[21]

coate

dSupra

-Gst

ent

vs.

Supra

-Gst

ent

117

vs.

58

double

-blind

Para

llel

gro

ups

sten

osi

sp

erce

nta

ge

NA

PA

TE

NC

Y,

2002

[22]

Logic

PT

Xpacl

itaxel

Elu

ting

Coro

nary

Ste

nts

vs.

unco

ate

dco

ntr

ol

sten

ts

24

vs.

26

double

blind

Para

llel

gro

ups

NA

NA

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

Ort

ola

ni

etal,

2007

[23]

Cypher

vs.

Vis

ion

NA

vs.

NA

single

-blind

Para

llel

gro

ups

Late

lum

enlo

ssN

A

Koch

iadakis

,2007

[24]

siro

lim

us-

eluti

ng

sten

tsvs.

bare

met

al

sten

t38

vs.

43

op

enP

ara

llel

gro

ups

inflam

mato

ryre

sponse

Gre

ece

Pach

eet

al,

2005

[25]

Cypher

vs.

BeS

tent

2250

vs.

250

op

enP

ara

llel

gro

ups

Bin

ary

rest

enosi

sG

erm

any

C-S

IRIU

S,

2004

[26]

coate

dB

x-V

EL

OC

ITY

vs.

Bx-V

EL

OC

ITY

50

vs.

50

double

-blind

Para

llel

gro

ups

Min

imal

lum

endia

met

erC

anada

SIR

IUS,

2003

[27,

28]

SE

Svs.

Bx

Vel

oci

ty533

vs.

525

double

-blind

Para

llel

gro

ups

Com

bin

ati

on

of

card

iacd

eath

,A

MI,

TV

R

Unit

edSta

tes

E-S

IRIU

S,

2003

[29]

coate

dB

xV

eloci

tyvs.

Bx

Vel

oci

ty175

vs.

177

op

enP

ara

llel

gro

ups

Min

imal

lum

endia

met

erE

uro

pe

RA

VE

L,

2002

[30,

31]

coate

dB

xV

eloci

tyvs.

Bx

Vel

oci

ty120

vs.

118

double

-blind

Para

llel

gro

ups

Late

lum

enlo

ssG

lobal

Zota

rolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

EN

DE

AV

OR

II,

2006

[32,

33,

34,

35]

AV

EZ

ota

rolim

us-

Elu

ting

Dri

ver

vs.

Dri

ver

598

vs.

599

double

-blind

Para

llel

gro

ups

targ

etves

sel

failure

worl

dw

ide


Table

1.2

:M

ain

study

char

act

eris

tics

-U

npar

ticu

lar

pat

ients

-co

mpar

ison

vers

us

pacl

itaxel

eluti

ng

sten

t

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

paclita

xel

elu

ting

stent

CoSta

rst

entvers

us

paclita

xelelu

ting

stent

Cost

ar

II,

2008

[1]

CoSta

rst

ent

(Conor

Med

Syst

ems)

vs.

Taxus

(Bost

on

Sci

enti

fic)

989

vs.

686

single

-blind

Para

llel

gro

ups

MA

CE

US,

Ger

many,

Bel

giu

m,

and

New

Zea

land

Rapam

ycin

elu

ting

stentvers

us

paclita

xelelu

ting

stent

Wes

sely

,2008

[2]

rapam

yci

np

oly

mer

-coate

ddru

g-e

luti

ng

sten

tvs.

pacl

itaxel

poly

mer

-coate

ddru

g-e

luti

ng

sten

t

NA

vs.

NA

NA

Para

llel

gro

ups

none

Ger

many

ISA

R-T

EST

-1,

2006

[3]

rapam

yci

n-e

luti

ng

sten

tY

ukon

vs.

Taxus

225

vs.

225

op

enP

ara

llel

gro

ups

in-s

tent

late

lum

enlo

ssG

erm

any

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

SO

RT

OU

TII

,2008

[4,

5]

Cypher

sten

tvs.

Taxus

sten

t(B

ost

on

Sci

enti

fic

Corp

)

1065

vs.

1033

op

enP

ara

llel

gro

ups

majo

radver

seca

rdia

cev

ents

Den

mark

.

Han,

2006

[6]

Cypher

vs.

Taxus

210

vs.

206

op

enP

ara

llel

gro

ups

none

Chin

a

Zhang

(SE

Svs

PE

S),

2006

[7]

Cypher

vs.

Taxus

246

vs.

203

op

enP

ara

llel

gro

ups

dea

th,A

MI,

TV

Rat

30day

sC

hin

a

RE

AL

ITY

,2006

[8]

Cypher

vs.

Taxus

701

vs.

685

op

enP

ara

llel

gro

ups

Bin

ary

rest

enosi

sE

uro

pe,

Lati

nA

mer

ica,

and

Asi

am

SIR

TA

X(W

indec

ker

),2005

[9]

Cypher

vs.

Taxus

503

vs.

509

single

-blind

Para

llel

gro

ups

card

iac

dea

th,

AM

I,T

LR

Sw

itze

rland

TA

Xi,

2005

[10,

11]

Cypher

vs.

Taxus

102

vs.

100

op

enP

ara

llel

gro

ups

Com

bin

ati

on

of

dea

th,A

MI,

TL

R,

sten

tth

rom

bosi

s

Sw

itze

rland.

BA

SK

ET

(vs

pacl

itaxel

),2005

[12]

Cypher

vs.

Taxus

264

vs.

281

op

enP

ara

llel

gro

ups

cost

-eff

ecti

ven

ess

Sw

itze

rland,

13

Table

1.3

:M

ain

study

char

act

eris

tics

-U

npar

ticu

lar

pat

ients

-co

mpar

ison

vers

us

siro

lim

us

eluti

ng

sten

t

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

siro

lim

us

elu

ting

stent

Bio

lim

us

elu

ting

stentvers

us

siro

lim

us

elu

ting

stent

LE

AD

ER

S,

2008

[1]

Bio

Matr

ixII

I(b

iolim

us-

eluti

ng

sten

tw

ithbio

deg

radable

poly

mer

)vs.

Cypher

SE

LE

CT

(sir

olim

us-

eluti

ng

sten

tw

ith

dura

ble

poly

mer

)

857

vs.

850

op

enass

esso

r-blind

Para

llel

gro

ups

card

iac

dea

th,

MI,

targ

etves

sel

reva

scula

risa

tion

Euro

pe

Zota

rolim

us

elu

ting

stentvers

us

siro

lim

us

elu

ting

stent

EN

DE

AV

OR

III,

2006

[2,

3]

AB

T-5

78

coate

dE

ndea

vor

vs.

Cypher

327

vs.

109

op

enP

ara

llel

gro

ups

in-s

egm

ent

late

lum

enlo

ssU

S


1.1 Main results for Unparticular patients

The meta-analysis of the available trials provide the results listed in tables 1.4 to 1.6 (page 15)and in the following graphs.

1.2 comparison versus bare-metal stent - summary of results

Dactinomycin eluting stent was superior to bare-metal stent in terms of MACE (RR=0.07,95% CI 0.04 to 0.11, p=0.0000, 1 trial) and CABG (RR=0.09, 95% CI 0.01 to 0.74, p=0.0250,1 trial) .However, no significant difference was found on all cause death (RR=0.44, 95% CI 0.03to 6.89, p=0.5549, 1 trial) , MI (fatal and non fatal) (RR=2.61, 95% CI 0.32 to 21.42, p=0.3714,1 trial) and target lesion revascularisation (RR=0.26, 95% CI 0.06 to 1.07, p=0.0624, 1 trial) .

Everolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.55,95% CI 0.37 to 0.82, p=0.0031, 4 trials) and target lesion revascularisation (RR=0.53, 95% CI0.31 to 0.91, p=0.0210, 4 trials) .However, no significant difference was found on all cause death(RR=1.00, 95% CI 0.34 to 2.96, p=0.9929, 3 trials) , cardiac death (RR=0.65, 95% CI 0.17 to2.40, p=0.5149, 2 trials) , MI (fatal and non fatal) (RR=0.66, 95% CI 0.34 to 1.26, p=0.2057,3 trials) and CABG (RR=0.35, 95% CI 0.01 to 17.25, p=0.5941, 1 trial) .

Paclitaxel eluting stent was superior to bare-metal stent in terms of target lesionrevascularisation (RR=0.27, 95% CI 0.19 to 0.40, p=0.0000, 3 trials) , in-lesion binary restenosis(RR=0.30, 95% CI 0.19 to 0.47, p=0.0000, 1 trial) and angiographic restenosis (RR=0.23, 95%CI 0.18 to 0.30, p=0.0000, 1 trial) .But paclitaxel eluting stent increased the risk of MI (fataland non fatal) (RR=2.77, 95% CI 1.06 to 7.21, p=0.0374, 4 trials) .However, no significantdifference was found on all cause death (RR=1.23, 95% CI 0.50 to 3.02, p=0.6560, 4 trials) ,cardiac death (RR=2.41, 95% CI 0.35 to 16.71, p=0.3745, 2 trials) , MACE (RR=0.66, 95%CI 0.40 to 1.07, p=0.0934, 4 trials) with a random effect model in reason of a heterogeneity(Het. p=0.0081) and target-vessel revascularization (RR=0.57, 95% CI 0.27 to 1.21, p=0.1422,2 trials) with a random effect model in reason of a heterogeneity (Het. p=0.0144) .

No significant difference was found between paclitaxel, non-polymeric eluting stentand bare-metal stent in terms of all cause death (RR=0.42, 95% CI 0.10 to 1.81, p=0.2461,4 trials) , MI (fatal and non fatal) (RR=0.97, 95% CI 0.19 to 4.99, p=0.9689, 4 trials) , MACE(RR=0.74, 95% CI 0.52 to 1.05, p=0.0958, 4 trials) and target lesion revascularisation (RR=0.42,95% CI 0.10 to 1.81, p=0.2461, 4 trials) .

Sirolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.38,95% CI 0.26 to 0.55, p=0.0000, 5 trials) , target-vessel revascularization (RR=0.41, 95% CI 0.30to 0.57, p=0.0000, 1 trial) and target lesion revascularisation (RR=0.25, 95% CI 0.16 to 0.39,p=0.0000, 5 trials) .However, no significant difference was found on all cause death (RR=1.42,95% CI 0.67 to 3.01, p=0.3585, 5 trials) , MI (fatal and non fatal) (RR=0.98, 95% CI 0.58 to1.66, p=0.9480, 4 trials) and CABG (RR=0.46, 95% CI 0.16 to 1.30, p=0.1426, 4 trials) .

Zotarolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.50,95% CI 0.36 to 0.71, p=0.0000, 1 trial) and angiographic restenosis (RR=0.39, 95% CI 0.28 to0.55, p=0.0000, 1 trial) .

1.3 comparison versus paclitaxel eluting stent - summary ofresults

CoStar stent was inferior to paclitaxel eluting stent in terms of MACE (RR=1.61, 95% CI1.16 to 2.23, p=0.0045, 1 trial) and target-vessel revascularization (RR=1.91, 95% CI 1.27 to

1.4. COMPARISON VERSUS SIROLIMUS ELUTING STENT - SUMMARY OF RESULTS15

2.89, p=0.0021, 1 trial) . No significant difference was found on all cause death (RR=0.69, 95%CI 0.20 to 2.39, p=0.5618, 1 trial) and MI (fatal and non fatal) (RR=1.47, 95% CI 0.82 to 2.65,p=0.1946, 1 trial) .

No significant difference was found between rapamycin eluting stent and paclitaxeleluting stent in terms of all cause death (RR=0.67, 95% CI 0.11 to 3.95, p=0.6552, 1 trial) .

No significant difference was found between sirolimus eluting stent and paclitaxel elut-ing stent in terms of all cause death (RR=0.98, 95% CI 0.64 to 1.50, p=0.9272, 7 trials) , cardiacdeath (RR=0.85, 95% CI 0.34 to 2.12, p=0.7231, 3 trials) , MI (fatal and non fatal) (RR=0.79,95% CI 0.59 to 1.07, p=0.1298, 7 trials) , MACE (RR=0.77, 95% CI 0.59 to 1.01, p=0.0587,4 trials) , target-vessel revascularization (RR=0.75, 95% CI 0.51 to 1.09, p=0.1319, 3 trials), target lesion revascularisation (RR=0.84, 95% CI 0.65 to 1.07, p=0.1531, 7 trials) , CABG(RR=1.96, 95% CI 0.07 to 57.80, p=0.6965, 1 trial) , in-lesion binary restenosis (RR=0.88, 95%CI 0.67 to 1.16, p=0.3591, 1 trial) and angiographic restenosis (RR=0.86, 95% CI 0.62 to 1.19,p=0.3692, 1 trial) .

1.4 comparison versus sirolimus eluting stent - summary ofresults

No significant difference was found between biolimus eluting stent and sirolimus elutingstent in terms of all cause death (RR=0.91, 95% CI 0.51 to 1.61, p=0.7437, 1 trial) , cardiacdeath (RR=0.66, 95% CI 0.34 to 1.29, p=0.2259, 1 trial) , MI (fatal and non fatal) (RR=1.25,95% CI 0.83 to 1.88, p=0.2925, 1 trial) , MACE (RR=0.92, 95% CI 0.69 to 1.23, p=0.5822, 1trial) , target-vessel revascularization (RR=0.80, 95% CI 0.53 to 1.22, p=0.2994, 1 trial) , targetlesion revascularisation (RR=0.87, 95% CI 0.57 to 1.35, p=0.5400, 1 trial) , CABG (RR=0.50,95% CI 0.20 to 1.22, p=0.1276, 1 trial) and angiographic restenosis (RR=0.64, 95% CI 0.33 to1.24, p=0.1833, 1 trial) .

Zotarolimus eluting stent was superior to sirolimus eluting stent in terms of MI (fataland non fatal) (RR=0.18, 95% CI 0.03 to 0.96, p=0.0451, 1 trial) .But zotarolimus eluting stentincreased the risk of in-lesion binary restenosis (RR=2.75, 95% CI 1.00 to 7.56, p=0.0499, 1trial) and angiographic restenosis (RR=4.33, 95% CI 1.05 to 17.91, p=0.0429, 1 trial) .How-ever, no significant difference was found on all cause death (RR=0.70, 95% CI 0.06 to 7.65,p=0.7700, 1 trial) , MACE (RR=0.97, 95% CI 0.47 to 2.02, p=0.9398, 1 trial) and target lesionrevascularisation (RR=1.84, 95% CI 0.64 to 5.24, p=0.2549, 1 trial) .

Table 1.4: Summary of all results for comparison versus bare-metal stent

Endpoint Effect 95% CI p ass p het (I2) k n

Dactinomycin eluting stent versus bare-metal stent

All cause death RR=0.44 0.03;6.89 0.5549 1.0000 (0.00) 1 343

MI (fatal and non fatal) RR=2.61 0.32;21.42 0.3714 1.0000 (0.00) 1 343

MACE RR=0.07 0.04;0.11 0.0000 1.0000 (0.00) 1 343

target lesion revascularisation RR=0.26 0.06;1.07 0.0624 1.0000 (0.00) 1 343

CABG RR=0.09 0.01;0.74 0.0250 1.0000 (0.00) 1 343

Everolimus eluting stent versus bare-metal stent


cardiac death RR=0.65 0.17;2.40 0.5149 0.4069 (0.00) 2 1276


continued...


Endpoint Effect 95% CI p ass p het k n

MACE RR=0.55 0.37;0.82 0.0031 0.8420 (0.00) 4 1373


CABG RR=0.35 0.01;17.25 0.5941 1.0000 (0.00) 1 300

Stent thrombosis (any, end offollow up)

RR=1.21 0.27;5.47 0.8023 0.9743 (0.00) 2 1024

4y stent thrombosis (ARC) RR=1.35 0.43;4.19 0.6088 1.0000 (0.00) 1 971

Acute stent thrombosis(<=24h)

RR=0.35 0.01;17.25 0.5941 1.0000 (0.00) 1 300

sub acute stent thrombosis(1-30 days)

RR=0.35 0.01;17.25 0.5941 1.0000 (0.00) 1 300

late stent thrombosis (31days -1year)

RR=0.35 0.02;5.45 0.4501 1.0000 (0.00) 1 300

Paclitaxel eluting stent versus bare-metal stent


cardiac death RR=2.41 0.35;16.71 0.3745 0.1648 (0.48) 2 1580


MACE RR=0.66 0.40;1.07 0.0934 0.0081 (0.75) 4 2164

target-vessel revascularization RR=0.57 0.27;1.21 0.1422 0.0144 (0.83) 2 1580


in-lesion binary restenosis RR=0.30 0.19;0.47 0.0000 1.0000 (0.00) 1 1314


RR=3.27 0.55;19.33 0.1920 0.0666 (0.58) 4 2137


RR=0.98 0.14;6.91 0.9838 1.0000 (0.00) 1 1314


RR=2.02 0.76;5.37 0.1563 0.8457 (0.00) 3 1911

angiographic restenosis RR=0.23 0.18;0.30 0.0000 1.0000 (0.00) 1 559

Paclitaxel, non-polymeric eluting stent versus bare-metal stent



MACE RR=0.74 0.52;1.05 0.0958 0.4882 (0.00) 4 1444



RR=0.97 0.26;3.61 0.9620 0.6062 (0.00) 4 1446


RR=0.57 0.08;4.00 0.5684 0.8414 (0.00) 3 1398

Sirolimus eluting stent versus bare-metal stent



MACE RR=0.38 0.26;0.55 0.0000 0.0741 (0.53) 5 2248



CABG RR=0.46 0.16;1.30 0.1426 0.6684 (0.00) 4 1748


RR=0.86 0.25;2.95 0.8044 0.7065 (0.00) 4 1748


RR=0.51 0.11;2.41 0.3950 0.9460 (0.00) 4 1748

Zotarolimus eluting stent versus bare-metal stent

MACE RR=0.50 0.36;0.71 0.0000 1.0000 (0.00) 1 1197


RR=0.43 0.11;1.65 0.2188 1.0000 (0.00) 1 1197

continued...




Table 1.5: Summary of all results for comparison versus paclitaxel eluting stent


CoStar stent versus paclitaxel eluting stent



MACE RR=1.61 1.16;2.23 0.0045 1.0000 (1.00) 1 1675



RR=4.16 0.50;34.49 0.1863 1.0000 (0.00) 1 1675


RR=0.69 0.04;11.07 0.7958 1.0000 (0.00) 1 1675

Rapamycin eluting stent versus paclitaxel eluting stent



RR=2.00 0.18;21.90 0.5703 1.0000 (0.00) 1 450

Sirolimus eluting stent versus paclitaxel eluting stent


cardiac death RR=0.85 0.34;2.12 0.7231 0.2939 (0.18) 3 4463


MACE RR=0.77 0.59;1.01 0.0587 0.3111 (0.16) 4 4875



CABG RR=1.96 0.07;57.80 0.6965 1.0000 (0.00) 1 202



RR=0.82 0.57;1.20 0.3108 0.6992 (0.00) 7 6038



RR=0.49 0.09;2.66 0.4079 1.0000 (0.00) 1 1353


RR=0.42 0.11;1.61 0.2063 1.0000 (0.00) 1 1353


RR=0.24 0.01;5.41 0.3728 1.0000 (0.00) 1 1353


Table 1.6: Summary of all results for comparison versus sirolimus eluting stent


Biolimus eluting stent versus sirolimus eluting stent


cardiac death RR=0.66 0.34;1.29 0.2259 1.0000 (0.00) 1 1707


MACE RR=0.92 0.69;1.23 0.5822 1.0000 (0.00) 1 1707



CABG RR=0.50 0.20;1.22 0.1276 1.0000 (0.00) 1 1707

continued...




RR=1.15 0.63;2.11 0.6547 1.0000 (0.00) 1 1707


RR=0.99 0.25;3.95 0.9907 1.0000 (0.00) 1 1707


Zotarolimus eluting stent versus sirolimus eluting stent



MACE RR=0.97 0.47;2.02 0.9398 1.0000 (0.00) 1 432




RR=0.35 0.01;17.54 0.5991 1.0000 (0.00) 1 432


Figure 1.1: Forest’s plot for all cause death

RR [95%CI] p k n p het I2

comparison versus bare-metal stent


0.44 [0.03;6.89] .55 1 343 1.00 0.00


1.00 [0.34;2.96] .99 3 1078 1.00 0.00

Paclitaxel eluting stent versus bare-metalstent

1.23 [0.50;3.02] .66 4 2137 .38 0.03

Paclitaxel, non-polymeric eluting stentversus bare-metal stent

0.42 [0.10;1.81] .25 4 1446 .92 0.00

Sirolimus eluting stent versus bare-metalstent

1.42 [0.67;3.01] .36 5 2248 .99 0.00

comparison versus paclitaxel eluting stent

CoStar stent versus paclitaxel elutingstent

0.69 [0.20;2.39] .56 1 1675 1.00 0.00

Rapamycin eluting stent versus pacli-taxel eluting stent

0.67 [0.11;3.95] .66 1 450 1.00 0.00

Sirolimus eluting stent versus paclitaxeleluting stent

0.98 [0.64;1.50] .93 7 6075 .67 0.00

comparison versus sirolimus eluting stent

Biolimus eluting stent versus sirolimuseluting stent

0.91 [0.51;1.61] .74 1 1707 1.00 0.00

Zotarolimus eluting stent versussirolimus eluting stent

0.70 [0.06;7.65] .77 1 432 1.00 0.00

1.00.1 10.0Relative risk

treatment worsens outcometreatment improves outcome

Results obtained with a fixed effect model except in case of heterogenity where a random model was used

RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total

number of patients involving in the pooled trials; p het: p-value of the hetereogenity test


Figure 1.2: Forest’s plot for cardiac death




0.65 [0.17;2.40] .51 2 1276 .41 0.00


2.41 [0.35;16.71] .37 2 1580 .16 0.48



0.85 [0.34;2.12] .72 3 4463 .29 0.18



0.66 [0.34;1.29] .23 1 1707 1.00 0.00







Figure 1.3: Forest’s plot for MI (fatal and non fatal)




2.61 [0.32;21.42] .37 1 343 1.00 0.00


0.66 [0.34;1.26] .21 3 1333 .62 0.00


2.77 [1.06;7.21] .04 4 2137 .68 0.00


0.97 [0.19;4.99] .97 4 1446 .82 0.00


0.98 [0.58;1.66] .95 4 1748 .58 0.00



1.47 [0.82;2.65] .19 1 1675 1.00 0.00


0.79 [0.59;1.07] .13 7 6075 1.00 0.00



1.25 [0.83;1.88] .29 1 1707 1.00 0.00


0.18 [0.03;0.96] .05 1 429 1.00 0.00







Figure 1.4: Forest’s plot for MACE




0.07 [0.04;0.11] .00 1 343 1.00 0.00


0.55 [0.37;0.82] .00 4 1373 .84 0.00


0.66 [0.40;1.07] .09 4 2164 .01 0.75


0.74 [0.52;1.05] .10 4 1444 .49 0.00


0.38 [0.26;0.55] .00 5 2248 .07 0.53


0.50 [0.36;0.71] .00 1 1197 1.00 0.00



1.61 [1.16;2.23] .00 1 1675 1.00 1.00


0.77 [0.59;1.01] .06 4 4875 .31 0.16



0.92 [0.69;1.23] .58 1 1707 1.00 0.00


0.97 [0.47;2.02] .94 1 432 1.00 0.00







Figure 1.5: Forest’s plot for target-vessel revascularization




0.57 [0.27;1.21] .14 2 1580 .01 0.83


0.41 [0.30;0.57] .00 1 1058 1.00 0.00



1.91 [1.27;2.89] .00 1 1675 1.00 0.00


0.75 [0.51;1.09] .13 3 4463 .45 0.00



0.80 [0.53;1.22] .30 1 1707 1.00 0.00

1.00.2 2.0 4.0Relative risk






Figure 1.6: Forest’s plot for target lesion revascularisation




0.26 [0.06;1.07] .06 1 343 1.00 0.00


0.53 [0.31;0.91] .02 4 1378 .77 0.00


0.27 [0.19;0.40] .00 3 1898 .92 0.00


0.42 [0.10;1.81] .25 4 1446 .92 0.00


0.25 [0.16;0.39] .00 5 2248 .18 0.37



0.84 [0.65;1.07] .15 7 6075 .62 0.00



0.87 [0.57;1.35] .54 1 1707 1.00 0.00


1.84 [0.64;5.24] .25 1 432 1.00 1.00







Figure 1.7: Forest’s plot for CABG




0.09 [0.01;0.74] .03 1 343 1.00 0.00


0.35 [0.01;17.25] .59 1 300 1.00 0.00


0.46 [0.16;1.30] .14 4 1748 .67 0.00



1.96 [0.07;57.80] .70 1 202 1.00 0.00



0.50 [0.20;1.22] .13 1 1707 1.00 0.00






Figure 1.8: Forest’s plot for in-lesion binary restenosis




0.30 [0.19;0.47] .00 1 1314 1.00 0.00



0.88 [0.67;1.16] .36 1 1911 1.00 0.00



2.75 [1.00;7.56] .05 1 376 1.00 0.00







Figure 1.9: Forest’s plot for stent thrombosis (any, end of follow up)




1.21 [0.27;5.47] .80 2 1024 .97 0.00


3.27 [0.55;19.33] .19 4 2137 .07 0.58


0.97 [0.26;3.61] .96 4 1446 .61 0.00


0.86 [0.25;2.95] .80 4 1748 .71 0.00


0.43 [0.11;1.65] .22 1 1197 1.00 0.00



4.16 [0.50;34.49] .19 1 1675 1.00 0.00

Rapamycin eluting stent versus pacli-taxel eluting stent

2.00 [0.18;21.90] .57 1 450 1.00 0.00


0.82 [0.57;1.20] .31 7 6038 .70 0.00



1.15 [0.63;2.11] .65 1 1707 1.00 0.00


0.35 [0.01;17.54] .60 1 432 1.00 0.00







Figure 1.10: Forest’s plot for 4y stent thrombosis (ARC)




1.35 [0.43;4.19] .61 1 971 1.00 0.00



0.73 [0.49;1.06] .10 7 6075 .65 0.00







Figure 1.11: Forest’s plot for acute stent thrombosis (<=24h)




0.35 [0.01;17.25] .59 1 300 1.00 0.00



0.49 [0.09;2.66] .41 1 1353 1.00 0.00








Figure 1.12: Forest’s plot for sub acute stent thrombosis (1-30 days)




0.35 [0.01;17.25] .59 1 300 1.00 0.00


0.98 [0.14;6.91] .98 1 1314 1.00 0.00



0.42 [0.11;1.61] .21 1 1353 1.00 0.00







Figure 1.13: Forest’s plot for late stent thrombosis (31days - 1year)




0.35 [0.02;5.45] .45 1 300 1.00 0.00


2.02 [0.76;5.37] .16 3 1911 .85 0.00


0.57 [0.08;4.00] .57 3 1398 .84 0.00


0.51 [0.11;2.41] .40 4 1748 .95 0.00



0.69 [0.04;11.07] .80 1 1675 1.00 0.00


0.24 [0.01;5.41] .37 1 1353 1.00 0.00



0.99 [0.25;3.95] .99 1 1707 1.00 0.00







Figure 1.14: Forest’s plot for angiographic restenosis




0.23 [0.18;0.30] .00 1 559 1.00 0.00


0.39 [0.28;0.55] .00 1 600 1.00 0.00



0.86 [0.62;1.19] .37 1 1911 1.00 0.00



0.64 [0.33;1.24] .18 1 484 1.00 0.00


4.33 [1.05;17.91] .04 1 376 1.00 0.00






29

2 Detailed results for comparison versus bare-metal

stent in unparticular patients

2.1 Available RCTs

This section gives details for trials evaluating drug eluting stent comparison versus bare-metalstent

A total of 22 RCTs which randomized 8989 patients were identified: 1 trial compared dacti-nomycin eluting stent with bare-metal stent , 5 trials compared everolimus eluting stent withbare-metal stent , 4 trials compared paclitaxel eluting stent with bare-metal stent , 4 trials com-pared paclitaxel, non-polymeric eluting stent with bare-metal stent , 7 trials compared sirolimuseluting stent with bare-metal stent and 1 trial compared zotarolimus eluting stent with bare-metal stent (see 2.1 page 30).

The average study size was 428 patients per arm (range 15 to 669 per arm). The first studywas published in 2002, and the last study was published in 2008. 10 trials were double blindand 5 were open-label in design. All included studies were reported in English language. Wefound one unpublished trial.

MACE data was reported in 19 trials; 17 trials reported data on target lesion revascularisa-tion ; 17 trials reported data on All cause death; 16 trials reported data on MI (fatal and nonfatal); 13 trials reported data on angiographic restenosis ; 6 trials reported data on CABG; 3trials reported data on cardiac death; 2 trials reported data on target-vessel revascularization;15 trials reported data on Stent thrombosis (any, end of follow up); 11 trials reported data onlate stent thrombosis (31days - 1year); 1 trials reported data on sub acute stent thrombosis (1-30days); 1 trials reported data on Acute stent thrombosis (¡=24h); and 1 trials reported data on4y stent thrombosis (ARC).

Following table 2.1 (page 30) summarized the main characteristics of the trials including inthis systematic review of RCTS of comparison versus bare-metal stent.

30 CHAPTER 2. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT

Table

2.1

:M

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tion:

681

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ting

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bare

-meta

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SP

IRIT

III,

2008

[3,

4]

n=

669

vs.

333

lesi

ons

28

mm

or

less

inle

ngth

and

wit

hre

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mary

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t:in

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men

tla

telo

ss65

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es,

US

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TU

RE

II,

2006

[5,

6,

7]

unpublish

edn

=43

vs.

21

Pati

ents

wit

hde

nov

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sions

inves

sels

wit

ha

refe

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2.1. AVAILABLE RCTS 31

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13]

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[17,

18,

19]

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2004

[20]

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[21]

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525

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[29]

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31]

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dw

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2.2. META-ANALYSIS RESULTS 35

2.2 Meta-analysis results

The results are detailed in table 2.2 (page 37). This table is followed by the Forest’s plotcorresponding to each endpoint.


The single study eligible for this comparison provided data on all cause death. There wasno statistically significant difference in all cause death between dactinomycin eluting stent andbare-metal stent, with a RR of 0.44 (95%CI 0.03 to 6.89, p=0.5549) in favour of dactinomycineluting stent. In other words, all cause death was slightly lower in the dactinomycin elutingstent group , but this was not statistically significant.

The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 2.61 (95% CI 0.32 to 21.42, p=0.3714).

The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of dactinomycin eluting stent in MACE, with a RRof 0.07 (95% CI 0.04 to 0.11, p=0.0000).

The single study eligible for this comparison provided data on target lesion revascular-isation . No statistically significant difference between the groups was found in target lesionrevascularisation , with a RR of 0.26 (95% CI 0.06 to 1.07, p=0.0624).

The single study eligible for this comparison provided data on CABG. The analysis detecteda statistically significant difference in favor of dactinomycin eluting stent in CABG, with a RRof 0.09 (95% CI 0.01 to 0.74, p=0.0250).


Data from 3 (among 5) trials evaluating all cause death were available. There was nostatistically significant difference in all cause death between everolimus eluting stent and bare-metal stent, with a RR of 1.00 (95%CI 0.34 to 2.96, p=0.9929) in favour of everolimus elutingstent. In other words, all cause death was slightly lower in the everolimus eluting stent group, but this was not statistically significant. No heterogeneity across these trials was detected (p=0.9953, I2 = 0.00%).

Data from 2 (among 5) trials evaluating cardiac death were available. When pooled to-gether, there was no statistically significant difference between the groups in cardiac death, witha RR of 0.65 (95% CI 0.17 to 2.40, p=0.5149). No heterogeneity across these trials was detected(p =0.4069, I2 = 0.00%).

Data from 3 (among 5) trials evaluating MI (fatal and non fatal) were available. Whenpooled together, there was no statistically significant difference between the groups in MI (fataland non fatal), with a RR of 0.66 (95% CI 0.34 to 1.26, p=0.2057). No heterogeneity acrossthese trials was detected (p =0.6190, I2 = 0.00%).

Data from 4 (among 5) trials evaluating MACE were available. The analysis detected astatistically significant difference in favor of everolimus eluting stent in MACE, with a RR of0.55 (95% CI 0.37 to 0.82, p=0.0031). No heterogeneity across these trials was detected (p=0.8420, I2 = 0.00%).

Data from 4 (among 5) trials evaluating target lesion revascularisation were available.The analysis detected a statistically significant difference in favor of everolimus eluting stentin target lesion revascularisation , with a RR of 0.53 (95% CI 0.31 to 0.91, p=0.0210). Noheterogeneity across these trials was detected (p =0.7667, I2 = 0.00%).

Only one of the 5 studies eligible for this comparison provided data on CABG. No statisti-cally significant difference between the groups was found in CABG, with a RR of 0.35 (95% CI0.01 to 17.25, p=0.5941).



All the 4 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between paclitaxeleluting stent and bare-metal stent, with a RR of 1.23 (95%CI 0.50 to 3.02, p=0.6560) in favourof bare-metal stent. In other words, all cause death was slightly lower in the bare-metal stentgroup , but this was not statistically significant. No heterogeneity across these trials was detected(p =0.3792, I2 = 0.03%).


All the 4 studies had extractable data about the number of participants with MI (fataland non fatal). The analysis detected a statistically significant difference in favor of bare-metal stent in MI (fatal and non fatal), with a RR of 2.77 (95% CI 1.06 to 7.21, p=0.0374). Noheterogeneity across these trials was detected (p =0.6839, I2 = 0.00%).

All the 4 studies had extractable data about the number of participants with MACE. Whenpooled together, there was no statistically significant difference between the groups in MACE,with a RR of 0.66 (95% CI 0.40 to 1.07, p=0.0934). A random effect model was used becausethere was a substantial statistical heterogeneity detected between the studies (p =0.0081, I2 =0.75%).

Data from 2 (among 4) trials evaluating target-vessel revascularization were available.When pooled together, there was no statistically significant difference between the groups intarget-vessel revascularization, with a RR of 0.57 (95% CI 0.27 to 1.21, p=0.1422). A randomeffect model was used because there was a substantial statistical heterogeneity detected betweenthe studies (p =0.0144, I2 = 0.83%).

Data from 3 (among 4) trials evaluating target lesion revascularisation were available.The analysis detected a statistically significant difference in favor of paclitaxel eluting stentin target lesion revascularisation , with a RR of 0.27 (95% CI 0.19 to 0.40, p=0.0000). Noheterogeneity across these trials was detected (p =0.9151, I2 = 0.00%).

Only one of the 4 studies eligible for this comparison provided data on in-lesion binaryrestenosis . The analysis detected a statistically significant difference in favor of paclitaxeleluting stent in in-lesion binary restenosis , with a RR of 0.30 (95% CI 0.19 to 0.47, p=0.0000).

Only one of the 4 studies eligible for this comparison provided data on angiographicrestenosis . The analysis detected a statistically significant difference in favor of paclitaxeleluting stent in angiographic restenosis , with a RR of 0.23 (95% CI 0.18 to 0.30, p=0.0000).


All the 4 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between paclitaxel,non-polymeric eluting stent and bare-metal stent, with a RR of 0.42 (95%CI 0.10 to 1.81,p=0.2461) in favour of paclitaxel, non-polymeric eluting stent. In other words, all cause deathwas slightly lower in the paclitaxel, non-polymeric eluting stent group , but this was not statis-tically significant. No heterogeneity across these trials was detected (p =0.9168, I2 = 0.00%).

All the 4 studies had extractable data about the number of participants with MI (fatal andnon fatal). When pooled together, there was no statistically significant difference between thegroups in MI (fatal and non fatal), with a RR of 0.97 (95% CI 0.19 to 4.99, p=0.9689). Noheterogeneity across these trials was detected (p =0.8212, I2 = 0.00%).

All the 4 studies had extractable data about the number of participants with MACE. Whenpooled together, there was no statistically significant difference between the groups in MACE,with a RR of 0.74 (95% CI 0.52 to 1.05, p=0.0958). No heterogeneity across these trials wasdetected (p =0.4882, I2 = 0.00%).

All the 4 studies had extractable data about the number of participants with target lesion


revascularisation . When pooled together, there was no statistically significant differencebetween the groups in target lesion revascularisation , with a RR of 0.42 (95% CI 0.10 to 1.81,p=0.2461). No heterogeneity across these trials was detected (p =0.9168, I2 = 0.00%).


Data from 5 (among 7) trials evaluating all cause death were available. There was nostatistically significant difference in all cause death between sirolimus eluting stent and bare-metal stent, with a RR of 1.42 (95%CI 0.67 to 3.01, p=0.3585) in favour of bare-metal stent.In other words, all cause death was slightly lower in the bare-metal stent group , but this wasnot statistically significant. No heterogeneity across these trials was detected (p =0.9903, I2 =0.00%).


Data from 5 (among 7) trials evaluating MACE were available. The analysis detected astatistically significant difference in favor of sirolimus eluting stent in MACE, with a RR of 0.38(95% CI 0.26 to 0.55, p=0.0000). No heterogeneity across these trials was detected (p =0.0741,I2 = 0.53%).

Only one of the 7 studies eligible for this comparison provided data on target-vessel revas-cularization. The analysis detected a statistically significant difference in favor of sirolimuseluting stent in target-vessel revascularization, with a RR of 0.41 (95% CI 0.30 to 0.57, p=0.0000).

Data from 5 (among 7) trials evaluating target lesion revascularisation were available.The analysis detected a statistically significant difference in favor of sirolimus eluting stentin target lesion revascularisation , with a RR of 0.25 (95% CI 0.16 to 0.39, p=0.0000). Noheterogeneity across these trials was detected (p =0.1772, I2 = 0.37%).

Data from 4 (among 7) trials evaluating CABG were available. When pooled together,there was no statistically significant difference between the groups in CABG, with a RR of 0.46(95% CI 0.16 to 1.30, p=0.1426). No heterogeneity across these trials was detected (p =0.6684,I2 = 0.00%).


The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of zotarolimus eluting stent in MACE, with a RR of0.50 (95% CI 0.36 to 0.71, p=0.0000).

The single study eligible for this comparison provided data on angiographic restenosis .The analysis detected a statistically significant difference in favor of zotarolimus eluting stent inangiographic restenosis , with a RR of 0.39 (95% CI 0.28 to 0.55, p=0.0000).

Table 2.2: Results details - Unparticular patients - comparison versus bare-metal stent

Comparison Endpoint Effect 95% CI p ass hom k n


All cause death RR=0.44 [0.03;6.89] 0.5549 1.0000 (I=0.00) 1 343

MI (fatal and non fatal) RR=2.61 [0.32;21.42] 0.3714 1.0000 (I=0.00) 1 343

MACE RR=0.07 [0.04;0.11] 0.0000 1.0000 (I=0.00) 1 343

target lesion revascularisation RR=0.26 [0.06;1.07] 0.0624 1.0000 (I=0.00) 1 343

CABG RR=0.09 [0.01;0.74] 0.0250 1.0000 (I=0.00) 1 343


continued...




cardiac death RR=0.65 [0.17;2.40] 0.5149 0.4069 (I=0.00) 2 1276


MACE RR=0.55 [0.37;0.82] 0.0031 0.8420 (I=0.00) 4 1373


CABG RR=0.35 [0.01;17.25] 0.5941 1.0000 (I=0.00) 1 300


RR=1.21 [0.27;5.47] 0.8023 0.9743 (I=0.00) 2 1024

4y stent thrombosis (ARC) RR=1.35 [0.43;4.19] 0.6088 1.0000 (I=0.00) 1 971


RR=0.35 [0.01;17.25] 0.5941 1.0000 (I=0.00) 1 300


RR=0.35 [0.01;17.25] 0.5941 1.0000 (I=0.00) 1 300


RR=0.35 [0.02;5.45] 0.4501 1.0000 (I=0.00) 1 300





MACE RR=0.66 [0.40;1.07] 0.0934 0.0081 (I=0.75) 4 2164

target-vessel revascularization RR=0.57 [0.27;1.21] 0.1422 0.0144 (I=0.83) 2 1580


in-lesion binary restenosis RR=0.30 [0.19;0.47] 0.0000 1.0000 (I=0.00) 1 1314


RR=3.27 [0.55;19.33] 0.1920 0.0666 (I=0.58) 4 2137


RR=0.98 [0.14;6.91] 0.9838 1.0000 (I=0.00) 1 1314


RR=2.02 [0.76;5.37] 0.1563 0.8457 (I=0.00) 3 1911

angiographic restenosis RR=0.23 [0.18;0.30] 0.0000 1.0000 (I=0.00) 1 559




MACE RR=0.74 [0.52;1.05] 0.0958 0.4882 (I=0.00) 4 1444



RR=0.97 [0.26;3.61] 0.9620 0.6062 (I=0.00) 4 1446


RR=0.57 [0.08;4.00] 0.5684 0.8414 (I=0.00) 3 1398




MACE RR=0.38 [0.26;0.55] 0.0000 0.0741 (I=0.53) 5 2248



CABG RR=0.46 [0.16;1.30] 0.1426 0.6684 (I=0.00) 4 1748


RR=0.86 [0.25;2.95] 0.8044 0.7065 (I=0.00) 4 1748


RR=0.51 [0.11;2.41] 0.3950 0.9460 (I=0.00) 4 1748

continued...




MACE RR=0.50 [0.36;0.71] 0.0000 1.0000 (I=0.00) 1 1197


RR=0.43 [0.11;1.65] 0.2188 1.0000 (I=0.00) 1 1197




Trial studied T. control T. RR [95%CI]


ACTION,2004 1/239 1/104 0.44 [0.03;6.89]

Global p ass= 0.5549 0.44 [0.03;6.89]


SPIRIT III,2008 8/655 4/321 0.98 [0.30;3.23]

FUTURE I,2004 1/27 0/15 1.11 [0.04;31.22]

SPIRIT I 0/28 0/32 1.14 [0.02;55.73]

Global p ass= 0.9929 1.00 [0.34;2.96]

Het. between 3 trials p=0.9953 I2=0.00


SCORE,2004 5/126 0/140 11.11 [0.61;201.36]

TAXUS IV,2004 9/662 8/652 1.11 [0.43;2.85]

TAXUS I,2003 0/31 0/30 0.97 [0.02;47.23]

TAXUS II,2003 0/226 2/270 0.30 [0.01;6.59]

Global p ass= 0.6560 1.23 [0.50;3.02]



DELIVER,2004 1/517 4/512 0.25 [0.03;2.21]

ELUTES,2004 1/152 0/38 0.50 [0.02;14.63]

ASPECT,2003 1/118 0/59 1.00 [0.03;29.38]

PATENCY,2002 0/24 1/26 0.54 [0.02;15.43]

Global p ass= 0.2461 0.42 [0.10;1.81]



Pache et al,2005 7/250 5/250 1.40 [0.45;4.35]

C-SIRIUS,2004 0/50 0/50 1.00 [0.02;49.42]

SIRIUS,2003 5/533 3/525 1.64 [0.39;6.83]

E-SIRIUS,2003 2/175 1/177 2.02 [0.19;22.11]

RAVEL,2002 2/120 2/118 0.98 [0.14;6.87]

Global p ass= 0.3585 1.42 [0.67;3.01]








SPIRIT III,2008 5/655 3/321 0.82 [0.20;3.40]

SPIRIT II 0/223 1/77 0.17 [0.01;5.10]

Global p ass= 0.5149 0.65 [0.17;2.40]



SCORE,2004 5/126 0/140 11.11 [0.61;201.36]

TAXUS IV,2004 /662 /652 1.27 [0.47;3.40]

Global p ass= 0.3745 2.41 [0.35;16.71]








ACTION,2004 6/239 1/104 2.61 [0.32;21.42]

Global p ass= 0.3714 2.61 [0.32;21.42]


SPIRIT III,2008 18/653 13/320 0.68 [0.34;1.37]

SPIRIT I 1/28 0/32 2.29 [0.08;65.59]

SPIRIT II 2/223 2/77 0.35 [0.05;2.41]

Global p ass= 0.2057 0.66 [0.34;1.26]



SCORE,2004 6/126 0/140 13.33 [0.75;236.34]

TAXUS IV,2004 5/662 2/652 2.46 [0.48;12.65]

TAXUS I,2003 0/31 0/30 0.97 [0.02;47.23]

TAXUS II,2003 6/226 3/270 2.39 [0.60;9.45]

Global p ass= 0.0374 2.77 [1.06;7.21]



DELIVER,2004 2/517 1/512 1.98 [0.18;21.78]

ELUTES,2004 0/152 0/38 0.25 [0.01;12.40]

ASPECT,2003 0/118 0/59 0.50 [0.01;24.89]

PATENCY,2002 0/24 0/26 1.08 [0.02;52.49]

Global p ass= 0.9689 0.97 [0.19;4.99]



C-SIRIUS,2004 1/50 2/50 0.50 [0.05;5.34]

SIRIUS,2003 15/533 17/525 0.87 [0.44;1.72]

E-SIRIUS,2003 8/175 4/177 2.02 [0.62;6.60]

RAVEL,2002 4/120 5/118 0.79 [0.22;2.86]

Global p ass= 0.9480 0.98 [0.58;1.66]








ACTION,2004 14/239 90/104 0.07 [0.04;0.11]

Global p ass= 0.0000 0.07 [0.04;0.11]


SPIRIT III,2008 39/653 33/320 0.58 [0.37;0.90]

FUTURE I,2004 2/26 1/14 1.08 [0.11;10.86]

SPIRIT I 2/28 6/32 0.38 [0.08;1.74]

SPIRIT II 6/223 5/77 0.41 [0.13;1.32]

Global p ass= 0.0031 0.55 [0.37;0.82]



SCORE,2004 37/126 35/140 1.17 [0.79;1.74]

TAXUS IV,2004 56/662 98/652 0.56 [0.41;0.77]

TAXUS I,2003 1/31 3/30 0.32 [0.04;2.93]

TAXUS II,2003 27/260 57/263 0.48 [0.31;0.73]

Global (random effect) p ass= 0.0934 0.66 [0.40;1.07]

fixed effect model p ass= 0.0000 0.66 [0.54;0.82]



DELIVER,2004 34/517 44/512 0.77 [0.50;1.18]

ELUTES,2004 15/152 7/38 0.54 [0.24;1.22]

ASPECT,2003 10/117 3/58 1.65 [0.47;5.77]

PATENCY,2002 3/24 6/26 0.54 [0.15;1.93]

Global p ass= 0.0958 0.74 [0.52;1.05]



Pache et al,2005 34/250 56/250 0.61 [0.41;0.90]

C-SIRIUS,2004 2/50 9/50 0.22 [0.05;0.98]

SIRIUS,2003 38/533 99/525 0.38 [0.27;0.54]

E-SIRIUS,2003 14/175 40/177 0.35 [0.20;0.63]

RAVEL,2002 7/120 35/118 0.20 [0.09;0.43]

Global p ass= 0.0000 0.38 [0.26;0.55]



ENDEAVOR II,2006 44/598 88/599 0.50 [0.36;0.71]

Global p ass= 0.0000 0.50 [0.36;0.71]







SCORE,2004 25/126 33/140 0.84 [0.53;1.33]

TAXUS IV,2004 /662 /652 0.39 [0.26;0.59]





SIRIUS,2003 46/533 110/525 0.41 [0.30;0.57]

Global p ass= 0.0000 0.41 [0.30;0.57]







ACTION,2004 3/239 5/104 0.26 [0.06;1.07]

Global p ass= 0.0624 0.26 [0.06;1.07]


SPIRIT III,2008 22/655 18/321 0.60 [0.33;1.10]

FUTURE I,2004 1/27 1/15 0.56 [0.04;8.26]

SPIRIT I 1/28 6/32 0.19 [0.02;1.49]

SPIRIT II 4/223 3/77 0.46 [0.11;2.01]

Global p ass= 0.0210 0.53 [0.31;0.91]



TAXUS IV,2004 20/662 74/652 0.27 [0.16;0.43]

TAXUS I,2003 0/31 3/30 0.16 [0.01;3.09]

TAXUS II,2003 11/260 38/263 0.29 [0.15;0.56]

Global p ass= 0.0000 0.27 [0.19;0.40]



DELIVER,2004 1/517 4/512 0.25 [0.03;2.21]

ELUTES,2004 1/152 0/38 0.50 [0.02;14.63]

ASPECT,2003 1/118 0/59 1.00 [0.03;29.38]

PATENCY,2002 0/24 1/26 0.54 [0.02;15.43]

Global p ass= 0.2461 0.42 [0.10;1.81]



Pache et al,2005 18/250 47/250 0.38 [0.23;0.64]

C-SIRIUS,2004 2/50 9/50 0.22 [0.05;0.98]

SIRIUS,2003 22/533 87/525 0.25 [0.16;0.39]

E-SIRIUS,2003 7/175 37/177 0.19 [0.09;0.42]

RAVEL,2002 0/120 27/118 0.02 [0.00;0.30]

Global p ass= 0.0000 0.25 [0.16;0.39]








ACTION,2004 1/239 5/104 0.09 [0.01;0.74]

Global p ass= 0.0250 0.09 [0.01;0.74]


SPIRIT II 0/223 0/77 0.35 [0.01;17.25]

Global p ass= 0.5941 0.35 [0.01;17.25]


C-SIRIUS,2004 1/50 0/50 2.00 [0.07;58.28]

SIRIUS,2003 3/533 8/525 0.37 [0.10;1.38]

E-SIRIUS,2003 0/175 3/177 0.17 [0.01;3.34]

RAVEL,2002 1/120 1/118 0.98 [0.06;15.54]

Global p ass= 0.1426 0.46 [0.16;1.30]







TAXUS IV,2004 /662 /652 0.30 [0.19;0.47]

Global p ass= 0.0000 0.30 [0.19;0.47]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk






SPIRIT III,2008 5/647 2/317 1.22 [0.24;6.28]

SPIRIT I 0/28 0/32 1.14 [0.02;55.73]

Global p ass= 0.8023 1.21 [0.27;5.47]



SCORE,2004 13/126 1/140 14.44 [1.92;108.85]

TAXUS IV,2004 4/662 5/652 0.79 [0.21;2.92]

TAXUS I,2003 0/31 0/30 0.97 [0.02;47.23]

TAXUS II,2003 5/226 0/270 11.95 [0.66;217.51]

Global p ass= 0.1920 3.27 [0.55;19.33]



DELIVER,2004 2/517 2/512 0.99 [0.14;7.00]

ELUTES,2004 1/152 1/38 0.25 [0.02;3.91]

ASPECT,2003 4/118 0/59 4.00 [0.22;74.41]

PATENCY,2002 0/24 0/26 1.08 [0.02;52.49]

Global p ass= 0.9620 0.97 [0.26;3.61]



C-SIRIUS,2004 1/50 1/50 1.00 [0.06;15.55]

SIRIUS,2003 2/533 4/525 0.49 [0.09;2.68]

E-SIRIUS,2003 2/175 0/177 4.05 [0.18;89.09]

RAVEL,2002 0/120 0/118 0.98 [0.02;49.15]

Global p ass= 0.8044 0.86 [0.25;2.95]



ENDEAVOR II,2006 3/598 7/599 0.43 [0.11;1.65]

Global p ass= 0.2188 0.43 [0.11;1.65]







SPIRIT III,2008 11/652 4/319 1.35 [0.43;4.19]

Global p ass= 0.6088 1.35 [0.43;4.19]






SPIRIT II 0/223 0/77 0.35 [0.01;17.25]

Global p ass= 0.5941 0.35 [0.01;17.25]






SPIRIT II 0/223 0/77 0.35 [0.01;17.25]

Global p ass= 0.5941 0.35 [0.01;17.25]


TAXUS IV,2004 /662 /652 0.98 [0.14;6.91]

Global p ass= 0.9838 0.98 [0.14;6.91]







SPIRIT II 1/223 1/77 0.35 [0.02;5.45]

Global p ass= 0.4501 0.35 [0.02;5.45]


TAXUS IV,2004 /662 /652 1.97 [0.68;5.72]

TAXUS I,2003 0/31 0/30 0.97 [0.02;47.23]

TAXUS II,2003 2/266 0/270 4.06 [0.18;89.62]

Global p ass= 0.1563 2.02 [0.76;5.37]



DELIVER,2004 1/522 1/519 0.99 [0.06;15.85]

ELUTES,2004 0/153 0/39 0.25 [0.01;12.65]

ASPECT,2003 0/117 0/48 0.41 [0.01;20.38]

Global p ass= 0.5684 0.57 [0.08;4.00]



C-SIRIUS,2004 0/50 1/50 0.50 [0.02;14.57]

SIRIUS,2003 1/533 3/525 0.33 [0.03;3.15]

E-SIRIUS,2003 0/175 0/177 1.01 [0.02;50.69]

RAVEL,2002 0/120 0/118 0.98 [0.02;49.15]

Global p ass= 0.3950 0.51 [0.11;2.41]




50 REFERENCES




TAXUS IV,2004 /292 /267 0.23 [0.18;0.30]

Global p ass= 0.0000 0.23 [0.18;0.30]


ENDEAVOR II,2006 40/298 103/302 0.39 [0.28;0.55]

Global p ass= 0.0000 0.39 [0.28;0.55]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk


References

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53

3 Detailed results for comparison versus paclitaxel

eluting stent in unparticular patients

3.1 Available RCTs

This section gives details for trials evaluating drug eluting stent comparison versus paclitaxeleluting stent

A total of 10 RCTs which randomized 8233 patients were identified: 1 trial compared CoStarstent with paclitaxel eluting stent , 2 trials compared rapamycin eluting stent with paclitaxeleluting stent and 7 trials compared sirolimus eluting stent with paclitaxel eluting stent (see 3.1page 54).

The average study size was 914 patients per arm (range 100 to 1065 per arm). The firststudy was published in 2005, and the last study was published in 2008.

All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.

All cause death data was reported in 9 trials; 8 trials reported data on MI (fatal and nonfatal); 7 trials reported data on target lesion revascularisation ; 5 trials reported data on MACE;4 trials reported data on target-vessel revascularization; 3 trials reported data on cardiac death;1 trials reported data on in-lesion binary restenosis ; 1 trials reported data on CABG; 1 trialsreported data on angiographic restenosis ; 9 trials reported data on Stent thrombosis (any, endof follow up); 7 trials reported data on 4y stent thrombosis (ARC); 2 trials reported data on latestent thrombosis (31days - 1year); 1 trials reported data on sub acute stent thrombosis (1-30days); and 1 trials reported data on Acute stent thrombosis (¡=24h).

Following table 3.1 (page 54) summarized the main characteristics of the trials including inthis systematic review of RCTS of comparison versus paclitaxel eluting stent.

54CHAPTER 3. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT

Table

3.1

:M

ain

study

char

act

eris

tics

-U

npar

ticu

lar

pat

ients

-co

mpar

ison

vers

us

pacl

itaxel

eluti

ng

sten

t

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

CoSta

rst

entvers

us

paclita

xelelu

ting

stent

Cost

ar

II,

2008

[1]

n=

989

vs.

686

pati

ent

under

goin

gp

ercu

taneo

us

coro

nary

inte

rven

tion

for

asi

ngle

lesi

on

per

ves

sel

inup

toth

ree

nati

ve

epic

ard

ial

ves

sels

CoSta

rst

ent

(Conor

Med

Syst

ems)

vs.

Taxus

(Bost

on

Sci

enti

fic)

mult

ives

sel

trea

tmen

t:21

single

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:M

AC

E71

centr

es,

US,

Ger

many,

Bel

giu

m,

and

New

Zea

land

Rapam

ycin

elu

ting

stentvers

us

paclita

xelelu

ting

stent

Wes

sely

,2008

[2]

n=

NA

vs.

NA

rapam

yci

np

oly

mer

-coate

ddru

g-e

luti

ng

sten

tvs.

pacl

itaxel

poly

mer

-coate

ddru

g-e

luti

ng

sten

t

NA

Para

llel

gro

ups

Pri

mary

endp

oin

t:none

1ce

ntr

es,

Ger

many

ISA

R-T

EST

-1,

2006

[3]

n=

225

vs.

225

stable

or

unst

able

angin

aor

ap

osi

tive

stre

sste

st,

stable

or

unst

able

angin

aor

ap

osi

tive

stre

sste

st

rapam

yci

n-e

luti

ng

sten

tY

ukon

vs.

Taxus

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:in

-ste

nt

late

lum

enlo

ss2

centr

es,

Ger

many

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

SO

RT

OU

TII

,2008

[4,

5]

n=

1065

vs.

1033

Unse

lect

edpati

ents

(incl

uded

ST

-seg

men

tel

evati

on

myoca

rdia

lin

farc

tion

(ST

EM

I),

non-S

TE

MI

or

unst

able

angin

ap

ecto

ris,

and

stable

angin

a)

Cypher

sten

tvs.

Taxus

sten

t(B

ost

on

Sci

enti

fic

Corp

)op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:m

ajo

radver

seca

rdia

cev

ents

5ce

ntr

es,

Den

mark

.

Han,

2006

[6]

n=

210

vs.

206

Mult

ives

sel

dis

ease

.Sta

ble

or

unst

able

AP

,no

AM

IC

ypher

vs.

Taxus

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:none

NA

,C

hin

a

Zhang

(SE

Svs

PE

S),

2006

[7]

n=

246

vs.

203

Unse

lect

edpati

ents

.Sta

ble

or

unst

able

AP

,A

CS

wit

hde

nov

oco

ronary

lesi

ons

Cypher

vs.

Taxus

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:dea

th,A

MI,

TV

Rat

30day

s1

centr

es,

Chin

a

cont

inue

d...


Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

RE

AL

ITY

,2006

[8]

n=

701

vs.

685

Rel

ati

vel

yunse

lect

edpati

ents

.Sta

ble

or

unst

able

docu

men

ted

sile

nt

isch

aem

ia,

no

AM

Iw

ith

1or

2de

nov

ole

sions

(2.2

5-3

.00

mm

india

met

er)

innati

ve

coro

nary

art

erie

s

Cypher

vs.

Taxus

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:B

inary

rest

enosi

s90

centr

es,

Euro

pe,

Lati

nA

mer

ica,

and

Asi

am

QC

Afo

llow

-up

dura

tion:

8m

onth

s

SIR

TA

X(W

indec

ker

),2005

[9]

n=

503

vs.

509

Unse

lect

edpati

ents

.Sta

ble

AP

,A

CS,

incl

udin

gA

MI.

at

least

one

lesi

on

wit

hst

enosi

sof

at

least

50

per

cent

ina

ves

sel

wit

ha

refe

rence

dia

met

erb

etw

een

2.2

5and

4.0

0m

mth

at

was

suit

able

for

sten

tim

pla

nta

tion

Cypher

vs.

Taxus

single

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:ca

rdia

cdea

th,

AM

I,T

LR

2ce

ntr

es,

Sw

itze

rland

TA

Xi,

2005

[10,

11]

n=

102

vs.

100

Unse

lect

edpati

ents

Cypher

vs.

Taxus

mult

ives

sel

trea

tmen

t:22.0

4op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:C

om

bin

ati

on

of

dea

th,A

MI,

TL

R,

sten

tth

rom

bosi

s1

centr

es,

Sw

itze

rland.

BA

SK

ET

(vs

pacl

itaxel

),2005

[12]

n=

264

vs.

281

Unse

lect

edpati

ents

;de-

nov

ole

sions

Cypher

vs.

Taxus

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:co

st-e

ffec

tiven

ess

1ce

ntr

es,

Sw

itze

rland,





The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between coStar stent and paclitaxeleluting stent, with a RR of 0.69 (95%CI 0.20 to 2.39, p=0.5618) in favour of coStar stent. Inother words, all cause death was slightly lower in the coStar stent group , but this was notstatistically significant.


The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of paclitaxel eluting stent in MACE, with a RR of1.61 (95% CI 1.16 to 2.23, p=0.0045).

The single study eligible for this comparison provided data on target-vessel revascular-ization. The analysis detected a statistically significant difference in favor of paclitaxel elutingstent in target-vessel revascularization, with a RR of 1.91 (95% CI 1.27 to 2.89, p=0.0021).


Only one of the 2 studies eligible for this comparison provided data on all cause death.There was no statistically significant difference in all cause death between rapamycin elutingstent and paclitaxel eluting stent, with a RR of 0.67 (95%CI 0.11 to 3.95, p=0.6552) in favourof rapamycin eluting stent. In other words, all cause death was slightly lower in the rapamycineluting stent group , but this was not statistically significant.


All the 7 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between sirolimuseluting stent and paclitaxel eluting stent, with a RR of 0.98 (95%CI 0.64 to 1.50, p=0.9272)in favour of sirolimus eluting stent. In other words, all cause death was slightly lower in thesirolimus eluting stent group , but this was not statistically significant. No heterogeneity acrossthese trials was detected (p =0.6672, I2 = 0.00%).



Data from 4 (among 7) trials evaluating MACE were available. When pooled together,there was no statistically significant difference between the groups in MACE, with a RR of 0.77(95% CI 0.59 to 1.01, p=0.0587). No heterogeneity across these trials was detected (p =0.3111,I2 = 0.16%).

Data from 3 (among 7) trials evaluating target-vessel revascularization were available.When pooled together, there was no statistically significant difference between the groups intarget-vessel revascularization, with a RR of 0.75 (95% CI 0.51 to 1.09, p=0.1319). No hetero-geneity across these trials was detected (p =0.4456, I2 = 0.00%).


All the 7 studies had extractable data about the number of participants with target lesionrevascularisation . When pooled together, there was no statistically significant differencebetween the groups in target lesion revascularisation , with a RR of 0.84 (95% CI 0.65 to 1.07,p=0.1531). No heterogeneity across these trials was detected (p =0.6239, I2 = 0.00%).


Only one of the 7 studies eligible for this comparison provided data on in-lesion binaryrestenosis . No statistically significant difference between the groups was found in in-lesionbinary restenosis , with a RR of 0.88 (95% CI 0.67 to 1.16, p=0.3591).

Only one of the 7 studies eligible for this comparison provided data on angiographicrestenosis . No statistically significant difference between the groups was found in angiographicrestenosis , with a RR of 0.86 (95% CI 0.62 to 1.19, p=0.3692).

Table 3.2: Results details - Unparticular patients - comparison versus paclitaxel eluting stent





MACE RR=1.61 [1.16;2.23] 0.0045 1.0000 (I=1.00) 1 1675



RR=4.16 [0.50;34.49] 0.1863 1.0000 (I=0.00) 1 1675


RR=0.69 [0.04;11.07] 0.7958 1.0000 (I=0.00) 1 1675




RR=2.00 [0.18;21.90] 0.5703 1.0000 (I=0.00) 1 450





MACE RR=0.77 [0.59;1.01] 0.0587 0.3111 (I=0.16) 4 4875



CABG RR=1.96 [0.07;57.80] 0.6965 1.0000 (I=0.00) 1 202



RR=0.82 [0.57;1.20] 0.3108 0.6992 (I=0.00) 7 6038



RR=0.49 [0.09;2.66] 0.4079 1.0000 (I=0.00) 1 1353


RR=0.42 [0.11;1.61] 0.2063 1.0000 (I=0.00) 1 1353


RR=0.24 [0.01;5.41] 0.3728 1.0000 (I=0.00) 1 1353






Costar II,2008 5/989 5/686 0.69 [0.20;2.39]

Global p ass= 0.5618 0.69 [0.20;2.39]


ISAR-TEST-1,2006 2/225 3/225 0.67 [0.11;3.95]

Global p ass= 0.6552 0.67 [0.11;3.95]


SORT OUT II,2008 0/1065 0/1033 0.97 [0.02;48.84]

Han,2006 3/210 4/206 0.74 [0.17;3.25]

Zhang (SES vs PES),2006 8/246 7/203 0.94 [0.35;2.56]

REALITY,2006 16/684 9/669 1.74 [0.77;3.91]

SIRTAX (Windecker),2005 5/503 11/509 0.46 [0.16;1.31]

TAXi,2005 0/102 0/100 0.98 [0.02;48.93]

BASKET (vs paclitaxel),20 10/264 11/281 0.97 [0.42;2.24]

Global p ass= 0.9272 0.98 [0.64;1.50]







SORT OUT II,2008 0/1065 0/1033 0.97 [0.02;48.84]

REALITY,2006 10/684 7/669 1.40 [0.53;3.65]


Global p ass= 0.7231 0.85 [0.34;2.12]








Costar II,2008 34/989 16/686 1.47 [0.82;2.65]

Global p ass= 0.1946 1.47 [0.82;2.65]


SORT OUT II,2008 0/1065 0/1033 0.97 [0.02;48.84]

Han,2006 2/210 3/206 0.65 [0.11;3.87]

Zhang (SES vs PES),2006 7/246 9/203 0.64 [0.24;1.69]

REALITY,2006 35/684 40/669 0.86 [0.55;1.33]


TAXi,2005 2/102 3/100 0.65 [0.11;3.83]


Global p ass= 0.1298 0.79 [0.59;1.07]







Costar II,2008 109/989 47/686 1.61 [1.16;2.23]

Global p ass= 0.0045 1.61 [1.16;2.23]


SORT OUT II,2008 0/1065 0/1033 0.97 [0.02;48.84]

Zhang (SES vs PES),2006 19/225 21/187 0.75 [0.42;1.36]

REALITY,2006 73/684 76/669 0.94 [0.69;1.27]


Global p ass= 0.0587 0.77 [0.59;1.01]








Costar II,2008 80/989 29/686 1.91 [1.27;2.89]

Global p ass= 0.0021 1.91 [1.27;2.89]


SORT OUT II,2008 0/1065 0/1033 0.97 [0.02;48.84]

REALITY,2006 14/684 12/669 1.14 [0.53;2.45]


Global p ass= 0.1319 0.75 [0.51;1.09]







SORT OUT II,2008 0/1065 0/1033 0.97 [0.02;48.84]

Han,2006 9/210 11/206 0.80 [0.34;1.90]

Zhang (SES vs PES),2006 14/246 16/203 0.72 [0.36;1.44]

REALITY,2006 41/684 41/669 0.98 [0.64;1.49]


TAXi,2005 2/102 1/100 1.96 [0.18;21.28]


Global p ass= 0.1531 0.84 [0.65;1.07]








TAXi,2005 1/102 0/100 1.96 [0.07;57.80]

Global p ass= 0.6965 1.96 [0.07;57.80]






REALITY,2006 86/970 95/941 0.88 [0.67;1.16]

Global p ass= 0.3591 0.88 [0.67;1.16]







Costar II,2008 6/989 1/686 4.16 [0.50;34.49]

Global p ass= 0.1863 4.16 [0.50;34.49]


ISAR-TEST-1,2006 2/225 1/225 2.00 [0.18;21.90]

Global p ass= 0.5703 2.00 [0.18;21.90]


SORT OUT II,2008 28/1065 30/1033 0.91 [0.54;1.50]

Han,2006 1/210 2/206 0.49 [0.04;5.37]

Zhang (SES vs PES),2006 2/225 3/187 0.55 [0.09;3.28]

REALITY,2006 5/684 13/669 0.38 [0.13;1.05]


TAXi,2005 1/102 0/100 1.96 [0.07;57.80]


Global p ass= 0.3108 0.82 [0.57;1.20]







SORT OUT II,2008 19/1065 19/1033 0.97 [0.52;1.82]

Han,2006 1/210 2/206 0.49 [0.04;5.37]

Zhang (SES vs PES),2006 2/246 3/203 0.55 [0.09;3.26]

REALITY,2006 6/684 18/669 0.33 [0.13;0.82]


TAXi,2005 2/102 2/100 0.98 [0.14;6.83]


Global p ass= 0.0995 0.73 [0.49;1.06]








REALITY,2006 2/684 4/669 0.49 [0.09;2.66]

Global p ass= 0.4079 0.49 [0.09;2.66]






REALITY,2006 3/684 7/669 0.42 [0.11;1.61]

Global p ass= 0.2063 0.42 [0.11;1.61]






Costar II,2008 1/989 1/686 0.69 [0.04;11.07]

Global p ass= 0.7958 0.69 [0.04;11.07]


REALITY,2006 0/684 2/669 0.24 [0.01;5.41]

Global p ass= 0.3728 0.24 [0.01;5.41]



64 REFERENCES




REALITY,2006 63/970 71/941 0.86 [0.62;1.19]

Global p ass= 0.3692 0.86 [0.62;1.19]



References

[1] Krucoff MW, Kereiakes DJ, Petersen JL, Mehran R, Hasselblad V, Lansky AJ, Fitzgerald PJ, Garg J,Turco MA, Simonton CA 3rd, Verheye S, Dubois CL, Gammon R, Batchelor WB, O’Shaughnessy CD,Hermiller JB Jr, Schofer J, Buchbinder M, Wijns W. A novel bioresorbable polymer paclitaxel-elutingstent for the treatment of single and multivessel coronary disease: primary results of the COSTAR (CobaltChromium Stent With Antiproliferative for Restenosis) II study.. J Am Coll Cardiol 2008 Apr 22;51:1543-52[PMID=18420096]

[2] Wessely R, Kastrati A, Mehilli J, Dibra A, Pache J, Schmig A. Randomized trial of rapamycin- andpaclitaxel-eluting stents with identical biodegradable polymeric coating and design.. Eur Heart J 2007Nov;28:2720-5 [PMID=17921531]

[3] Mehilli J, Kastrati A, Wessely R, Dibra A, Hausleiter J, Jaschke B, Dirschinger J, Schmig A. Randomizedtrial of a nonpolymer-based rapamycin-eluting stent versus a polymer-based paclitaxel-eluting stent for thereduction of late lumen loss.. Circulation 2006;113:273-9 [PMID=16391155]

[4] Galloe AM.. prospective multi-center, large-scale, randomized trialof paclitaxel- and sirolimus-eluting stentsin real-world lesions. Annual Scientifi c Meeting of the Transcatheter CardiovascularTherapeutics; Wash-ington, DC; Oct 2227, 2006

[5] Galle AM, Thuesen L, Kelbaek H, Thayssen P, Rasmussen K, Hansen PR, Bligaard N, Saunamki K, JunkerA, Aare J, Abildgaard U, Ravkilde J, Engstrm T, Jensen JS, Andersen HR, Btker HE, Galatius S, KristensenSD, Madsen JK, Krusell LR, Abildstrm SZ, Step. Comparison of paclitaxel- and sirolimus-eluting stents ineveryday clinical practice: the SORT OUT II randomized trial.. JAMA 2008;299:409-16 [PMID=18230778]

[6] Han YL, Wang XZ, Jing QM, Wang SL, Ma YY, Luan B. [Comparison of Rapamycin and Paclitaxel elutingstent in patients with multi-vessel coronary disease]. Zhonghua Xin Xue Guan Bing Za Zhi 2006;34:123-6[PMID=16626577]

[7] Zhang Q, Zhang RY, Zhang JS, Hu J, Yang ZK, Ni J, Fang YH, Zhang X, Shen WF. One-year clinicaloutcomes of Chinese sirolimus-eluting stent in the treatment of unselected patients with coronary arterydisease.. Chin Med J (Engl) 2006;119:165-8 [PMID=16455001]

[8] Morice MC, Colombo A, Meier B, Serruys P, Tamburino C, Guagliumi G, Sousa E, Stoll HP. Sirolimus- vspaclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlledtrial.. JAMA 2006;295:895-904 [PMID=16493102]

[9] Windecker S, Remondino A, Eberli FR, Jni P, Rber L, Wenaweser P, Togni M, Billinger M, Tller D, SeilerC, Roffi M, Corti R, Stsch G, Maier W, Lscher T, Hess OM, Egger M, Meier B. Sirolimus-eluting andpaclitaxel-eluting stents for coronary revascularization.. N Engl J Med 2005;353:653-62 [PMID=16105989]

REFERENCES 65

[10] Goy JJ, Stauffer JC, Siegenthaler M, Benot A, Seydoux C. A prospective randomized comparison betweenpaclitaxel and sirolimus stents in the real world of interventional cardiology: the TAXi trial.. J Am CollCardiol 2005;45:308-11 [PMID=15653032]

[11] Berger A, Stauffer JC, Seydoux C, Siegenthaler M, Benot A, Goy JJ. Three-year follow-up of the firstprospective randomized comparison between paclitaxel and sirolimus stents: the TAXi-LATE trial.. CatheterCardiovasc Interv 2007 Aug 1;70:163-6 [PMID=17630653]

[12] Kaiser C, Brunner-La Rocca HP, Buser PT, Bonetti PO, Osswald S, Linka A, Bernheim A, Zutter A,Zellweger M, Grize L, Pfisterer ME. Incremental cost-effectiveness of drug-eluting stents compared with athird-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitts Trial(BASKET).. Lancet 2005;366:921-9 [PMID=16154019]

66 CHAPTER 4. DETAILS FOR COMPARISON VERSUS SIROLIMUS ELUTING STENT

4 Detailed results for comparison versus sirolimus

eluting stent in unparticular patients

4.1 Available RCTs

This section gives details for trials evaluating drug eluting stent comparison versus sirolimuseluting stent

A total of 2 RCTs which randomized 2143 patients were identified: 1 trial compared biolimuseluting stent with sirolimus eluting stent and 1 trial compared zotarolimus eluting stent withsirolimus eluting stent (see 4.1 page 67).

The average study size was 1071 patients per arm (range 109 to 857 per arm). The firststudy was published in 2006, and the last study was published in 2008.


Target lesion revascularisation data was reported in 2 trials; 2 trials reported data on MI(fatal and non fatal); 2 trials reported data on MACE; 2 trials reported data on angiographicrestenosis ; 2 trials reported data on All cause death; 1 trials reported data on target-vesselrevascularization; 1 trials reported data on in-lesion binary restenosis ; 1 trials reported data oncardiac death; 1 trials reported data on CABG; 2 trials reported data on Stent thrombosis (any,end of follow up); and 1 trials reported data on late stent thrombosis (31days - 1year).

Following table 4.1 (page 67) summarized the main characteristics of the trials including inthis systematic review of RCTS of comparison versus sirolimus eluting stent.


Table

4.1

:M

ain

study

char

act

eris

tics

-U

npar

ticu

lar

pat

ients

-co

mpar

ison

vers

us

siro

lim

us

eluti

ng

sten

t

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Bio

lim

us

elu

ting

stentvers

us

siro

lim

us

elu

ting

stent

LE

AD

ER

S,

2008

[1]

n=

857

vs.

850

pati

ents

aged

18

yea

rsor

old

erw

ith

chro

nic

stable

coro

nary

art

ery

dis

ease

or

acu

teco

ronary

syndro

mes

Bio

Matr

ixII

I(b

iolim

us-

eluti

ng

sten

tw

ithbio

deg

radable

poly

mer

)vs.

Cypher

SE

LE

CT

(sir

olim

us-

eluti

ng

sten

tw

ith

dura

ble

poly

mer

)m

ult

ives

sel

trea

tmen

t:34.2

op

enass

esso

r-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:ca

rdia

cdea

th,

MI,

tar-

get

ves

sel

reva

scula

risa

tion

10

centr

es,

Euro

pe

Zota

rolim

us

elu

ting

stentvers

us

siro

lim

us

elu

ting

stent

EN

DE

AV

OR

III,

2006

[2,

3]

n=

327

vs.

109

single

de

nov

ole

sions

innati

ve

coro

nary

art

erie

s2.5

-3.5

mm

india

met

erA

BT

-578

coate

dE

ndea

vor

vs.

Cypher

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:in

-seg

men

tla

telu

men

loss

29

centr

es,

US





The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between biolimus eluting stent andsirolimus eluting stent, with a RR of 0.91 (95%CI 0.51 to 1.61, p=0.7437) in favour of biolimuseluting stent. In other words, all cause death was slightly lower in the biolimus eluting stentgroup , but this was not statistically significant.

The single study eligible for this comparison provided data on cardiac death. No statis-tically significant difference between the groups was found in cardiac death, with a RR of 0.66(95% CI 0.34 to 1.29, p=0.2259).


The single study eligible for this comparison provided data on MACE. No statisticallysignificant difference between the groups was found in MACE, with a RR of 0.92 (95% CI 0.69to 1.23, p=0.5822).

The single study eligible for this comparison provided data on target-vessel revascular-ization. No statistically significant difference between the groups was found in target-vesselrevascularization, with a RR of 0.80 (95% CI 0.53 to 1.22, p=0.2994).


The single study eligible for this comparison provided data on CABG. No statisticallysignificant difference between the groups was found in CABG, with a RR of 0.50 (95% CI 0.20to 1.22, p=0.1276).

The single study eligible for this comparison provided data on angiographic restenosis .No statistically significant difference between the groups was found in angiographic restenosis ,with a RR of 0.64 (95% CI 0.33 to 1.24, p=0.1833).


The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between zotarolimus eluting stentand sirolimus eluting stent, with a RR of 0.70 (95%CI 0.06 to 7.65, p=0.7700) in favour ofzotarolimus eluting stent. In other words, all cause death was slightly lower in the zotarolimuseluting stent group , but this was not statistically significant.

The single study eligible for this comparison provided data on MI (fatal and non fatal).The analysis detected a statistically significant difference in favor of zotarolimus eluting stent inMI (fatal and non fatal), with a RR of 0.18 (95% CI 0.03 to 0.96, p=0.0451).



The single study eligible for this comparison provided data on in-lesion binary restenosis. The analysis detected a statistically significant difference in favor of sirolimus eluting stent inin-lesion binary restenosis , with a RR of 2.75 (95% CI 1.00 to 7.56, p=0.0499).


The single study eligible for this comparison provided data on angiographic restenosis .The analysis detected a statistically significant difference in favor of sirolimus eluting stent inangiographic restenosis , with a RR of 4.33 (95% CI 1.05 to 17.91, p=0.0429).

Table 4.2: Results details - Unparticular patients - comparison versus sirolimus eluting stent






MACE RR=0.92 [0.69;1.23] 0.5822 1.0000 (I=0.00) 1 1707



CABG RR=0.50 [0.20;1.22] 0.1276 1.0000 (I=0.00) 1 1707


RR=1.15 [0.63;2.11] 0.6547 1.0000 (I=0.00) 1 1707


RR=0.99 [0.25;3.95] 0.9907 1.0000 (I=0.00) 1 1707





MACE RR=0.97 [0.47;2.02] 0.9398 1.0000 (I=0.00) 1 432




RR=0.35 [0.01;17.54] 0.5991 1.0000 (I=0.00) 1 432





LEADERS,2008 22/857 24/850 0.91 [0.51;1.61]

Global p ass= 0.7437 0.91 [0.51;1.61]


ENDEAVOR III,2006 2/320 1/112 0.70 [0.06;7.65]

Global p ass= 0.7700 0.70 [0.06;7.65]







LEADERS,2008 14/857 21/850 0.66 [0.34;1.29]

Global p ass= 0.2259 0.66 [0.34;1.29]






LEADERS,2008 49/857 39/850 1.25 [0.83;1.88]

Global p ass= 0.2925 1.25 [0.83;1.88]


ENDEAVOR III,2006 2/316 4/113 0.18 [0.03;0.96]

Global p ass= 0.0451 0.18 [0.03;0.96]







LEADERS,2008 78/857 84/850 0.92 [0.69;1.23]

Global p ass= 0.5822 0.92 [0.69;1.23]


ENDEAVOR III,2006 25/320 9/112 0.97 [0.47;2.02]

Global p ass= 0.9398 0.97 [0.47;2.02]






LEADERS,2008 38/857 47/850 0.80 [0.53;1.22]

Global p ass= 0.2994 0.80 [0.53;1.22]







LEADERS,2008 37/857 42/850 0.87 [0.57;1.35]

Global p ass= 0.5400 0.87 [0.57;1.35]


ENDEAVOR III,2006 21/320 4/112 1.84 [0.64;5.24]

Global p ass= 0.2549 1.84 [0.64;5.24]






LEADERS,2008 7/857 14/850 0.50 [0.20;1.22]

Global p ass= 0.1276 0.50 [0.20;1.22]






ENDEAVOR III,2006 33/282 4/94 2.75 [1.00;7.56]

Global p ass= 0.0499 2.75 [1.00;7.56]

1.0 5.0 10.0Relative risk






LEADERS,2008 22/857 19/850 1.15 [0.63;2.11]

Global p ass= 0.6547 1.15 [0.63;2.11]


ENDEAVOR III,2006 0/320 0/112 0.35 [0.01;17.54]

Global p ass= 0.5991 0.35 [0.01;17.54]






LEADERS,2008 4/857 4/850 0.99 [0.25;3.95]

Global p ass= 0.9907 0.99 [0.25;3.95]



74 REFERENCES




LEADERS,2008 14/253 20/231 0.64 [0.33;1.24]

Global p ass= 0.1833 0.64 [0.33;1.24]


ENDEAVOR III,2006 26/282 2/94 4.33 [1.05;17.91]

Global p ass= 0.0429 4.33 [1.05;17.91]



References

[1] Windecker S, Serruys PW, Wandel S, Buszman P, Trznadel S, Linke A, Lenk K, Ischinger T, Klauss V, EberliF, Corti R, Wijns W, Morice MC, di Mario C, Davies S, van Geuns RJ, Eerdmans P, van Es GA, MeierB, Jni P. Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durablepolymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial.. Lancet 2008 Aug31;: [PMID=18765162]

[2] Miyazawa A, Ako J, Hongo Y, Hur SH, Tsujino I, Courtney BK, Hassan AH, Kandzari DE, Honda Y,Fitzgerald PJ, , . Comparison of vascular response to zotarolimus-eluting stent versus sirolimus-eluting stent:intravascular ultrasound results from ENDEAVOR III.. Am Heart J 2008;155:108-13. [PMID=18082499]

[3] Kandzari DE, Leon MB, Popma JJ, Fitzgerald PJ, O’Shaughnessy C, Ball MW, Turco M, ApplegateRJ, Gurbel PA, Midei MG, Badre SS, Mauri L, Thompson KP, LeNarz LA, Kuntz RE. Comparison ofzotarolimus-eluting and sirolimus-eluting stents in patients with native coronary artery disease: a random-ized controlled trial.. J Am Coll Cardiol 2006;48:2440-7 [PMID=17174180]

75

5 Ongoing studies of Unparticular patients

5.1 List of ongoing trials

A total of 19 studies were still ongoing at the date of this report. A list of these ongoing studieswith a brief description is given table 5.1.

Table 5.1: Ongoing studies for Unparticular patients

Study Description

BASKET-PROVE (2008)[1]

Cypher vs. Vision

GENESIS Trial CP-01 (0)[] NCT00322569

Corio Pimecrolimus vs. CoStar

patients with de novo lesions of the native coronary arteries

ZoMaxx phase 2 (0)[] NCT00140101

ZoMaxx drug-eluting stent vs. TAXUS Express2

de Novo Coronary Artery Lesions

PROTECT (0)[] NCT00476957

Medtronic Endeavor Zotarolimus Eluting Coronary Stent System vs.Cordis Cypher Sirolimus-eluting Coronary Stent

unselected patients

PEPCAD III (0)[] NCT00473499

DEBlue stent vs. Cypher

stenoses in native coronary arteries

MIDCAB Versus DES inProximal LAD Lesions (0)[] NCT00299429

sirolimus-coated stent vs. minimally invasive bypass surgery

patients with isolated proximal left anterior descending coronary arter-ies

RES-ELUTION (0)[] NCT00606333

Conor Cobalt Chromium Sirolimus-eluting Coronary Stent System vs.TAXUS Liberte Paclitaxel-eluting Coronary Stent System

De Novo Native Coronary Artery Lesions

FEMH-93005 (0)[] NCT00190099

vs.

ZEST (0)[] NCT00418067

ABT 578-eluting balloon expandable stent (Medtronic) vs. CYPHERor TAXUS Libert

real-world practice

TRIAS-Low-Risk (0)[]

vs.

COMBAT (0)[]

PCI vs. CABG

Korean Randomized Study(0)[]

PCI vs. CABG

Munich Study (0)[]

sirolimus vs. CABG

REVASCULARIZE (0)[]

PCI vs. CABG

SORT OUT IV (0)[] NCT00552877

Xience V vs. Cypher Select+

unselected patients with coronary artery disease

PERSEUS WH (0)[] NCT00484315

TAXUS ElementTM vs. TAXUS Express 2

De Novo Coronary Artery Lesions

continued...

76 REFERENCES

Study Description

FRE-RACE (0)[] NCT00130546

Cypher select vs. Taxus

de novo native coronary lesions with two or more coronary arterystenoses

ENDEAVOR IV (0)[2] NCT00217269

Endeavor vs. Taxus

single de novo lesions in native coronary arteries with a reference vesseldiameter (RVD) of 2.5-3.5 mm

SPIRIT IV (0)[] NCT00307047

XIENCE V Everolimus Eluting Coronary Stent System vs. TAXUSEXPRESS2 Paclitaxel Eluting Coronary Stent System (TAXUS).

subjects with reference vessel diameters (RVD) 2.5 mm to 4.25 mm andlesion lengths <= 28 mm

References

[1] Pfisterer M, Bertel O, Bonetti PO, Brunner-La Rocca HP, Eberli FR, Erne P, Galatius S, Hornig B, KiowskiW, Pachinger O, Pedrazzini G, Rickli H, De Servi S, Kaiser C, , . Drug-eluting or bare-metal stents forlarge coronary vessel stenting? The BASKET-PROVE (PROspective Validation Examination) trial: studyprotocol and design.. Am Heart J 2008;155:609-14. [PMID=18371466]

[2] Leon MB. Endeavor Clinical Program Overview,. FDA Advisory Panel, October 10th, 2007

Part II

Diabetic patients

77

79

6 Overview of available evidence for diabetic

patients


paclitaxel eluting stent and 1 the comparison versus rapamycin eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 7 (page 92)

for comparison versus bare-metal stent, in section 8 (page 103 ) for comparison versus paclitaxeleluting stent and in section 9 (page 110 ) for comparison versus rapamycin eluting stent.

The average study size was 174 patients per arm (range 19 to 192 per arm). The first studywas published in 2003, and the last study was published in 2008. 5 trials were double blind and8 were open-label in design. All included studies were reported in English language. We did notfound any unpublished trial.

80 CHAPTER 6. OVERVIEW OF AVAILABLE EVIDENCE FOR DIABETIC PATIENTS

Table

6.1

:M

ain

study

char

acte

rist

ics

-D

iabet

icpat

ients

-co

mpar

ison

vers

us

bare

-met

alst

ent

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

bare

-meta

lst

ent

Paclita

xelelu

ting

stentvers

us

bare

-meta

lst

ent

TA

XU

SV

I(d

iab

etic

s),

2005

[1]

TA

XU

Svs.

Expre

ss2

sten

t39

vs.

50

double

-blind

Para

llel

gro

ups

TV

RE

uro

pe

TA

XU

SV

(dia

bet

ics)

,2005

[2]

TA

XU

Svs.

BM

S178

vs.

171

double

-blind

Para

llel

gro

ups

TV

RU

nit

edSta

tes

TA

XU

SIV

(dia

bet

ics)

,2005

[3]

TA

XU

Svs.

EX

PR

ESS

155

vs.

163

double

-blind

Para

llel

gro

ups

TV

RU

nit

edSta

tes

TA

XU

SII

(dia

bet

ics)

,2003

[4]

TA

XU

Svs.

NIR

sten

t37

vs.

41

double

-blind

Para

llel

gro

ups

Neo

inti

mal

pro

life

rati

on

Euro

pe

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

DE

SSE

RT

,2008

[5]

Cypher

andC

ypher

Sel

ect

vs.

Sonic

(Cord

is)

75

vs.

75

single

-blind

Para

llel

gro

ups

in-s

tent

late

loss

Italy

SC

OR

PIU

S,

2007

[6,

7]

Cypher

vs.

Bx-V

eloci

ty98

vs.

102

op

enP

ara

llel

gro

ups

Late

lum

enlo

ssG

erm

any

SE

S-S

MA

Rt

(dia

bet

ics)

,2005

[8]

Cypher

vs.

Bx

Sonic

29

vs.

45

single

-blind

Para

llel

gro

ups

Bin

ary

rest

enosi

sIt

aly

DE

CO

DE

,2005

[9]

CY

PH

ER

(Up

to3

sten

tsp

erpati

ent

wer

eallow

ed)

vs.

Bx

VE

LO

CIT

Y(U

pto

3st

ents

per

pati

ent

wer

eallow

ed)

54

vs.

29

op

enP

ara

llel

gro

ups

Late

lum

enlo

ssU

S,

Asi

a/P

aci

fic

DIA

BE

TE

S,

2005

[10,

11]

Cypher

vs.

Bx

Vel

oci

ty/Sonic

80

vs.

80

op

enP

ara

llel

gro

ups

Late

lum

enlo

ssSpanis

h

Rav

el(d

iab

etic

s),

2004

[12]

coate

dB

xvel

oci

tyvs.

Bx

VE

LO

CIT

Y19

vs.

25

NA

Para

llel

gro

ups

NA

Euro

pe

SIR

IUS

(dia

bet

ics)

,2003

[13,

14]

SE

Svs.

BM

S131

vs.

148

double

-blind

Para

llel

gro

ups

NA

US

81

Table

6.2

:M

ain

study

chara

cter

isti

cs-

Dia

bet

icpat

ients

-co

mpar

ison

vers

us

pacl

itaxel

eluti

ng

sten

t

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

paclita

xel

elu

ting

stent

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

Tom

ai,

2008

[1]

siro

lim

us-

eluti

ng

sten

tvs.

pacl

itaxel

-elu

ting

sten

t

60

vs.

60

NA

Cro

ssov

erin

-ste

nt

late

lum

inal

loss

Italy

Kim

,2008

[2]

Cypher

vs.

Taxus

85

vs.

84

op

enP

ara

llel

gro

ups

late

lum

enlo

ssK

ore

a

RE

AL

ITY

(dia

bet

ics)

,2006

[3]

SE

Svs.

PE

S187

vs.

192

op

enP

ara

llel

gro

ups

NA

worl

dw

ide

SIR

TA

Xdia

bet

ics,

2005

[4,

5]

Cypher

vs.

Taxus

108

vs.

93

single

-blind

Para

llel

gro

ups

card

iac

dea

th,

AM

I,T

LR

Sw

itze

rland

ISA

R-D

IAB

ET

ES,

2005

[6]

Taxus

vs.

Cypher

125

vs.

125

op

enP

ara

llel

gro

ups

Late

lum

enlo

ssG

erm

any

TA

xi

(dia

bet

ics)

,0

[]unpublish

edSE

Svs.

PE

S33

vs.

36

op

enP

ara

llel

gro

ups

NA

Sw

itze

rland


Table

6.3

:M

ain

study

chara

cter

isti

cs-

Dia

bet

icpat

ients

-co

mpar

ison

vers

us

rapam

yci

nel

uti

ng

sten

t

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

rapam

ycin

elu

ting

stent

Paclita

xelelu

ting

stentvers

us

rapam

ycin

elu

ting

stent

ISA

R-t

est

(dia

bet

ics)

,2006

[1]

Taxus

vs.

rapam

yci

nst

ent

73

vs.

58

op

enP

ara

llel

gro

ups

NA

ger

many

6.1. MAIN RESULTS FOR DIABETIC PATIENTS 83

6.1 Main results for Diabetic patients

The meta-analysis of the available trials provide the results listed in tables 6.4 to 6.6 (page 83)and in the following graphs.


Paclitaxel eluting stent was superior to bare-metal stent in terms of target lesion revas-cularisation (RR=0.40, 95% CI 0.27 to 0.60, p=0.0000, 4 trials) and angiographic restenosis(RR=0.17, 95% CI 0.08 to 0.37, p=0.0000, 3 trials) .

Sirolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.46,95% CI 0.32 to 0.67, p=0.0000, 3 trials) , 2 yr MACE (RR=0.31, 95% CI 0.16 to 0.59, p=0.0000,1 trial) , target-vessel revascularization (RR=0.25, 95% CI 0.10 to 0.61, p=0.0026, 1 trial) , 2yr TLR (RR=0.22, 95% CI 0.10 to 0.50, p=0.0000, 1 trial) , target lesion revascularisation(RR=0.24, 95% CI 0.13 to 0.44, p=0.0000, 5 trials) and angiographic restenosis (RR=0.18, 95%CI 0.11 to 0.29, p=0.0000, 4 trials) .However, no significant difference was found on all causedeath (RR=0.83, 95% CI 0.21 to 3.34, p=0.7950, 3 trials) , MI (fatal and non fatal) (RR=0.80,95% CI 0.42 to 1.55, p=0.5128, 2 trials) and CABG (RR=1.03, 95% CI 0.02 to 51.15, p=0.9884,1 trial) .


No significant difference was found between sirolimus eluting stent and paclitaxel elutingstent in terms of all cause death (RR=0.71, 95% CI 0.23 to 2.21, p=0.5568, 2 trials) , MI(fatal and non fatal) (RR=1.50, 95% CI 0.43 to 5.25, p=0.5297, 2 trials) , MACE (RR=1.64,95% CI 0.29 to 9.19, p=0.5759, 1 trial) , target lesion revascularisation (RR=0.72, 95% CI 0.40to 1.29, p=0.2697, 5 trials) , CABG (RR=0.99, 95% CI 0.02 to 49.23, p=0.9953, 1 trial) andangiographic restenosis (RR=0.40, 95% CI 0.08 to 1.98, p=0.2591, 1 trial) .

6.4 comparison versus rapamycin eluting stent - summary ofresults

Data were insufficient to compare Paclitaxel eluting stent to rapamycin eluting stent.There was an eligible trial but it did not provided sufficient information about the endpointsconsidered by this meta-analysis.









MACE RR=0.46 0.32;0.67 0.0000 0.3847 (0.00) 3 372

continued...



2 yr MACE RR=0.31 0.16;0.59 0.0000 1.0000 (0.00) 1 158


2 yr TLR RR=0.22 0.10;0.50 0.0000 1.0000 (1.00) 1 158


CABG RR=1.03 0.02;51.15 0.9884 1.0000 (0.00) 1 138


RR=0.80 0.16;4.08 0.7916 0.9641 (0.00) 3 295


RR=1.03 0.02;51.15 0.9884 1.0000 (0.00) 1 138


RR=1.03 0.09;11.21 0.9820 0.5687 (0.00) 2 296


RR=0.51 0.05;5.60 0.5849 0.9988 (0.00) 2 296







MACE RR=1.64 0.29;9.19 0.5759 1.0000 (0.00) 1 69


CABG RR=0.99 0.02;49.23 0.9953 1.0000 (0.00) 1 169


RR=0.25 0.01;5.49 0.3791 1.0000 (0.00) 1 250



RR=0.41 0.11;1.51 0.1790 0.5890 (0.00) 3 830


Table 6.6: Summary of all results for comparison versus rapamycin eluting stent


Paclitaxel eluting stent versus rapamycin eluting stent

No data were presented in the trial identified

6.4. COMPARISON VERSUS RAPAMYCIN ELUTING STENT - SUMMARY OF RESULTS85





0.83 [0.21;3.34] .80 3 295 .40 0.00



0.71 [0.23;2.21] .56 2 419 .80 0.00

comparison versus rapamycin eluting stent










0.80 [0.42;1.55] .51 2 212 .96 0.00



1.50 [0.43;5.25] .53 2 419 .74 0.00












0.46 [0.32;0.67] .00 3 372 .38 0.00



1.64 [0.29;9.19] .58 1 69 1.00 0.00







Figure 6.4: Forest’s plot for 2 yr MACE




0.31 [0.16;0.59] .00 1 158 1.00 0.00



1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk










0.25 [0.10;0.61] .00 1 138 1.00 0.00



1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk





Figure 6.6: Forest’s plot for 2 yr TLR




0.22 [0.10;0.50] .00 1 158 1.00 1.00



1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk










0.40 [0.27;0.60] .00 4 834 .38 0.03


0.24 [0.13;0.44] .00 5 499 .13 0.43



0.72 [0.40;1.29] .27 5 1068 .23 0.29











1.03 [0.02;51.15] .99 1 138 1.00 0.00



0.99 [0.02;49.23] 1.00 1 169 1.00 0.00












0.80 [0.16;4.08] .79 3 295 .96 0.00



0.25 [0.01;5.49] .38 1 250 1.00 0.00












0.25 [0.01;5.49] .38 1 250 1.00 0.00












1.03 [0.02;51.15] .99 1 138 1.00 0.00












1.03 [0.09;11.21] .98 2 296 .57 0.00













0.51 [0.05;5.60] .58 2 296 1.00 0.00



0.41 [0.11;1.51] .18 3 830 .59 0.00











0.17 [0.08;0.37] .00 3 485 .92 0.00


0.18 [0.11;0.29] .00 4 422 .44 0.00



0.40 [0.08;1.98] .26 1 169 1.00 1.00









stent in diabetic patients

7.1 Available RCTs


A total of 11 RCTs which randomized 1824 patients were identified: 4 trials comparedpaclitaxel eluting stent with bare-metal stent and 7 trials compared sirolimus eluting stent withbare-metal stent (see 7.1 page 93).


Target lesion revascularisation data was reported in 3 trials; 3 trials reported data on MACE;3 trials reported data on All cause death; 2 trials reported data on MI (fatal and non fatal); 2trials reported data on angiographic restenosis ; 1 trials reported data on target-vessel revascu-larization; 1 trials reported data on CABG; 1 trials reported data on 2 yr TLR ; 1 trials reporteddata on 2 yr MACE ; 3 trials reported data on Stent thrombosis (any, end of follow up); 2 trialsreported data on sub acute stent thrombosis (1-30 days); 2 trials reported data on late stentthrombosis (31days - 1year); and 1 trials reported data on Acute stent thrombosis (¡=24h).

Following table 7.1 (page 93) summarized the main characteristics of the trials including inthis systematic review of RCTS of comparison versus bare-metal stent.


Table

7.1

:M

ain

study

char

acte

rist

ics

-D

iabet

icpat

ients

-co

mpar

ison

vers

us

bare

-met

alst

ent

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Paclita

xelelu

ting

stentvers

us

bare

-meta

lst

ent

TA

XU

SV

I(d

iab

etic

s),

2005

[1]

n=

39

vs.

50

Dia

bet

icpati

ents

wit

hst

able

or

unst

able

AP

,si

lent

isch

aem

iaw

ith

long,

com

ple

xco

ronary

art

ery

lesi

ons

TA

XU

Svs.

Expre

ss2

sten

tdouble

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:T

VR

44

centr

es,

Euro

pe

TA

XU

SV

(dia

bet

ics)

,2005

[2]

n=

178

vs.

171

Dia

bet

icpati

ents

wit

hst

able

or

unst

able

AP

,si

lent

isch

aem

iaw

ith

com

ple

xor

pre

vio

usl

yunst

udie

dle

sions

(req

uir

ing

2.2

5-m

m,

4.0

-mm

,and/or

mult

iple

sten

ts)

TA

XU

Svs.

BM

Sdouble

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:T

VR

66

centr

es,

Unit

edSta

tes

TA

XU

SIV

(dia

bet

ics)

,2005

[3]

n=

155

vs.

163

Dia

bet

icpati

ents

wit

hst

able

or

unst

able

AP

,pro

voka

ble

isch

aem

iaw

ith

asi

ngle

,pre

vio

usl

yuntr

eate

dco

ronary

-art

ery

sten

osi

s(v

esse

ldia

met

er,

2.5

to3.7

5m

m;

lesi

on

length

,10

to28

mm

)

TA

XU

Svs.

EX

PR

ESS

double

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:T

VR

73

centr

es,

Unit

edSta

tes

TA

XU

SII

(dia

bet

ics)

,2003

[4]

n=

37

vs.

41

Dia

bet

icpati

ents

wit

hst

able

or

unst

able

AP

,si

lent

isch

aem

ia;

single

de

nov

ota

rget

lesi

on

wit

hes

tim

ate

dst

enosi

s>

50%

and

<99%

,

TA

XU

Svs.

NIR

sten

tdouble

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:N

eoin

tim

al

pro

life

ra-

tion

38

centr

es,

Euro

pe

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

DE

SSE

RT

,2008

[5]

n=

75

vs.

75

de

nov

ole

sions

of

dia

bet

icpati

ents

trea

ted

wit

hin

sulin

and/or

ora

lanti

dia

bet

ics

for

>3

month

s

Cypher

andC

ypher

Sel

ect

vs.

Sonic

(Cord

is)

single

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:in

-ste

nt

late

loss

mult

icen

tre,

Italy

QC

Afo

llow

-up

dura

tion:

8m

onth

s

SC

OR

PIU

S,

2007

[6,

7]

n=

98

vs.

102

pati

ents

wit

hdia

bet

esand

de

nov

oco

ronary

art

ery

lesi

ons

Cypher

vs.

Bx-V

eloci

tyop

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:L

ate

lum

enlo

ss16

centr

es,

Ger

many

cont

inue

d...


Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

SE

S-S

MA

Rt

(dia

bet

ics)

,2005

[8]

n=

29

vs.

45

Dia

bet

icpati

ents

wit

hde

nov

ota

rget

lesi

on

<=

2.7

5m

min

dia

met

erin

anati

ve

coro

nary

art

ery

that

could

be

com

ple

tely

cover

edby

asi

ngle

sten

t(m

axim

um

length

33

mm

)

Cypher

vs.

Bx

Sonic

single

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:B

inary

rest

enosi

s20

centr

es,

Italy

DE

CO

DE

,2005

[9]

n=

54

vs.

29

Sta

ble

or

unst

able

angin

ain

dia

bet

icpati

ents

wit

hw

ith

up

to2

de

nov

ole

sions

inup

to2

nati

ve

coro

nary

ves

sels

CY

PH

ER

(Up

to3

sten

tsp

erpati

ent

wer

eallow

ed)

vs.

Bx

VE

LO

CIT

Y(U

pto

3st

ents

per

pati

ent

wer

eallow

ed)

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:L

ate

lum

enlo

ssN

A,

US,

Asi

a/P

aci

fic

DIA

BE

TE

S,

2005

[10,

11]

n=

80

vs.

80

de

nov

ole

sions

innati

ve

coro

nary

art

erie

sin

1,

2,

or

3nati

ve

ves

sels

wit

hsy

mpto

ms

or

ob

ject

ive

evid

ence

of

isch

emia

;ves

sel

size

smaller

than

4.0

mm

Cypher

vs.

Bx

Vel

oci

ty/Sonic

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:L

ate

lum

enlo

ss4

centr

es,

Spanis

h

Rav

el(d

iab

etic

s),

2004

[12]

n=

19

vs.

25

sub

gro

ups

of

dia

bet

icpati

ents

wit

hde

nov

onati

ve

coro

nary

art

eryle

sions

2.5

to3.5

mm

india

met

erby

vis

uala

sses

smen

tth

at

could

be

cover

edby

an

18-m

mst

ent

coate

dB

xvel

oci

tyvs.

Bx

VE

LO

CIT

YN

AP

ara

llel

gro

ups

Pri

mary

endp

oin

t:,

Euro

pe

SIR

IUS

(dia

bet

ics)

,2003

[13,

14]

n=

131

vs.

148

sub

gro

up

of

dia

bet

ics

pati

ents

of

SIR

IUS

study

SE

Svs.

BM

Sdouble

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:,

US





All the 4 studies had extractable data about the number of participants with target lesionrevascularisation . The analysis detected a statistically significant difference in favor of pacli-taxel eluting stent in target lesion revascularisation , with a RR of 0.40 (95% CI 0.27 to 0.60,p=0.0000). No heterogeneity across these trials was detected (p =0.3757, I2 = 0.03%).

Data from 3 (among 4) trials evaluating angiographic restenosis were available. Theanalysis detected a statistically significant difference in favor of paclitaxel eluting stent in an-giographic restenosis , with a RR of 0.17 (95% CI 0.08 to 0.37, p=0.0000). No heterogeneityacross these trials was detected (p =0.9222, I2 = 0.00%).


Data from 3 (among 7) trials evaluating all cause death were available. There was nostatistically significant difference in all cause death between sirolimus eluting stent and bare-metal stent, with a RR of 0.83 (95%CI 0.21 to 3.34, p=0.7950) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant. No heterogeneity across these trials was detected (p=0.3992, I2 = 0.00%).


Data from 3 (among 7) trials evaluating MACE were available. The analysis detected astatistically significant difference in favor of sirolimus eluting stent in MACE, with a RR of 0.46(95% CI 0.32 to 0.67, p=0.0000). No heterogeneity across these trials was detected (p =0.3847,I2 = 0.00%).

Only one of the 7 studies eligible for this comparison provided data on 2 yr MACE . Theanalysis detected a statistically significant difference in favor of sirolimus eluting stent in 2 yrMACE , with a RR of 0.31 (95% CI 0.16 to 0.59, p=0.0000).


Only one of the 7 studies eligible for this comparison provided data on 2 yr TLR . Theanalysis detected a statistically significant difference in favor of sirolimus eluting stent in 2 yrTLR , with a RR of 0.22 (95% CI 0.10 to 0.50, p=0.0000).



Data from 4 (among 7) trials evaluating angiographic restenosis were available. Theanalysis detected a statistically significant difference in favor of sirolimus eluting stent in angio-graphic restenosis , with a RR of 0.18 (95% CI 0.11 to 0.29, p=0.0000). No heterogeneity acrossthese trials was detected (p =0.4447, I2 = 0.00%).


Table 7.2: Results details - Diabetic patients - comparison versus bare-metal stent








MACE RR=0.46 [0.32;0.67] 0.0000 0.3847 (I=0.00) 3 372

2 yr MACE RR=0.31 [0.16;0.59] 0.0000 1.0000 (I=0.00) 1 158


2 yr TLR RR=0.22 [0.10;0.50] 0.0000 1.0000 (I=1.00) 1 158


CABG RR=1.03 [0.02;51.15] 0.9884 1.0000 (I=0.00) 1 138


RR=0.80 [0.16;4.08] 0.7916 0.9641 (I=0.00) 3 295


RR=1.03 [0.02;51.15] 0.9884 1.0000 (I=0.00) 1 138


RR=1.03 [0.09;11.21] 0.9820 0.5687 (I=0.00) 2 296


RR=0.51 [0.05;5.60] 0.5849 0.9988 (I=0.00) 2 296





DESSERT,2008 3/68 2/70 1.54 [0.27;8.96]

SES-SMARt (diabetics),200 0/29 1/45 0.78 [0.03;22.39]

DECODE,2005 0/54 2/29 0.13 [0.01;2.88]

Global p ass= 0.7950 0.83 [0.21;3.34]








DESSERT,2008 11/68 14/70 0.81 [0.40;1.65]


Global p ass= 0.5128 0.80 [0.42;1.55]







DESSERT,2008 15/68 28/70 0.55 [0.32;0.94]


DIABETES,2005 9/80 29/80 0.31 [0.16;0.61]

Global p ass= 0.0000 0.46 [0.32;0.67]







DIABETES,2005 10/78 33/80 0.31 [0.16;0.59]

Global p ass= 0.0000 0.31 [0.16;0.59]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk






DESSERT,2008 5/68 21/70 0.25 [0.10;0.61]

Global p ass= 0.0026 0.25 [0.10;0.61]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk





DIABETES,2005 6/78 28/80 0.22 [0.10;0.50]

Global p ass= 0.0000 0.22 [0.10;0.50]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk






TAXUS VI (diabetics),2005 /39 /50 0.20 [0.05;0.82]

TAXUS V (diabetics),2005 /178 /171 0.54 [0.31;0.95]

TAXUS IV (diabetics),2005 /155 /163 0.37 [0.20;0.69]

TAXUS II (diabetics),2003 /37 /41 0.16 [0.03;0.95]

Global p ass= 0.0000 0.40 [0.27;0.60]



DESSERT,2008 4/68 21/70 0.20 [0.07;0.54]


DECODE,2005 5/54 8/29 0.34 [0.12;0.93]

DIABETES,2005 /80 /80 0.20 [0.08;0.50]

Ravel (diabetics),2004 /19 /25 0.07 [0.02;0.27]

Global p ass= 0.0000 0.24 [0.13;0.44]







DESSERT,2008 0/68 0/70 1.03 [0.02;51.15]

Global p ass= 0.9884 1.03 [0.02;51.15]







DESSERT,2008 1/68 1/70 1.03 [0.07;16.13]


DECODE,2005 0/54 0/29 0.54 [0.01;26.37]

Global p ass= 0.7916 0.80 [0.16;4.08]







DESSERT,2008 0/68 0/70 1.03 [0.02;51.15]

Global p ass= 0.9884 1.03 [0.02;51.15]






DESSERT,2008 1/68 0/70 2.06 [0.07;60.37]

DIABETES,2005 0/78 1/80 0.51 [0.02;15.07]

Global p ass= 0.9820 1.03 [0.09;11.21]




REFERENCES 101




DESSERT,2008 0/68 1/70 0.51 [0.02;15.09]

DIABETES,2005 0/78 1/80 0.51 [0.02;15.07]

Global p ass= 0.5849 0.51 [0.05;5.60]







TAXUS VI (diabetics),2005 /39 /50 0.20 [0.06;0.66]

TAXUS IV (diabetics),2005 /155 /163 0.16 [0.06;0.43]

TAXUS II (diabetics),2003 /37 /41 0.07 [0.00;34.60]

Global p ass= 0.0000 0.17 [0.08;0.37]



SCORPIUS,2007 6/68 32/76 0.21 [0.09;0.47]

SES-SMARt (diabetics),200 /29 /45 0.19 [0.06;0.60]

DIABETES,2005 6/80 29/80 0.21 [0.09;0.47]

Ravel (diabetics),2004 /19 /25 0.06 [0.02;0.24]

Global p ass= 0.0000 0.18 [0.11;0.29]




References

[1] Dawkins KD, Grube E, Guagliumi G, Banning AP, Zmudka K, Colombo A, Thuesen L, Hauptman K, MarcoJ, Wijns W, Popma JJ, Koglin J, Russell ME. Clinical efficacy of polymer-based paclitaxel-eluting stents inthe treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for theuse of drug-eluting stents in contemporary clinical practice.. Circulation 2005;112:3306-13 [PMID=16286586]

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[2] Ellis SG. TAXUS V trial global results: expanding the randomizeddata. 2005 American College of Cardiol-ogyAnnual Scientific Session

[3] Hermiller JB, Raizner A, Cannon L, Gurbel PA, Kutcher MA, Wong SC, Russell ME, Ellis SG, MehranR, Stone GW. Outcomes with the polymer-based paclitaxel-eluting TAXUS stent in patients with diabetesmellitus: the TAXUS-IV trial.. J Am Coll Cardiol 2005;45:1172-9 [PMID=15837245]

[4] Hermiller J.. Diabetic results: Taxus II, IV and VI. TCT [PMID=0]

[5] Maresta A, Varani E, Balducelli M, Varbella F, Lettieri C, Uguccioni L, Sangiorgio P, Zoccai GB. Com-parison of effectiveness and safety of sirolimus-eluting stents versus bare-metal stents in patients with dia-betes mellitus (from the Italian Multicenter Randomized DESSERT Study).. Am J Cardiol 2008;101:1560-6[PMID=18489933]

[6] Baumgart D.. One year results of the SCORPIUS-Trial - a Germanmulticenter investigation on the effectiveness of sirolimus-elutingstents in diabetic patients. Annual Scientifi c Meeting of theTranscatheterCardiovascular Therapeutics. Washington, DC;Oct 2227, 2006. Abstract 288.

[7] Baumgart D, Klauss V, Baer F, Hartmann F, Drexler H, Motz W, Klues H, Hofmann S, Vlker W, Pfan-nebecker T, Stoll HP, Nickenig G. One-year results of the SCORPIUS study: a German multicenter inves-tigation on the effectiveness of sirolimus-eluting stents in diabetic patients.. J Am Coll Cardiol 2007 Oct23;50:1627-34 [PMID=17950142]

[8] Ortolani P, Ardissino D, Cavallini C, Bramucci E, Indolfi C, Aquilina M, Marzocchi A. Effect of sirolimus-eluting stent in diabetic patients with small coronary arteries (a SES-SMART substudy).. Am J Cardiol2005;96:1393-8 [PMID=16275185]

[9] Chan C, Zambahari R, Kaul U, Cohen SA, Buchbinder M.. Outcomesin diabetic patients with multivesseldisease and long lesions: resultsfrom the DECODE study. Am J Cardiol 2005; 96 (suppl 7A): 31H

[10] Sabat M, Jimnez-Quevedo P, Angiolillo DJ, Gmez-Hospital JA, Alfonso F, Hernndez-Antoln R, GoicoleaJ, Bauelos C, Escaned J, Moreno R, Fernndez C, Fernndez-Avils F, Macaya C. Randomized comparison ofsirolimus-eluting stent versus standard stent for percutaneous coronary revascularization in diabetic patients:the diabetes and sirolimus-eluting stent (DIABETES) trial.. Circulation 2005;112:2175-83 [PMID=16203930]

[11] Jimnez-Quevedo P, Sabat M, Angiolillo DJ, Alfonso F, Hernndez-Antoln R, SanMartn M, Gmez-HospitalJA, Bauelos C, Escaned J, Moreno R, Fernndez C, Fernndez-Avils F, Macaya C. Long-term clinical benefitof sirolimus-eluting stent implantation in diabetic patients with de novo coronary stenoses: long-term resultsof the DIABETES trial.. Eur Heart J 2007;28:1946-52 [PMID=17562666]

[12] Abizaid A, Costa MA, Blanchard D, Albertal M, Eltchaninoff H, Guagliumi G, Geert-Jan L, Abizaid AS,Sousa AG, Wuelfert E, Wietze L, Sousa JE, Serruys PW, Morice MC. Sirolimus-eluting stents inhibitneointimal hyperplasia in diabetic patients. Insights from the RAVEL Trial.. Eur Heart J 2004;25:107-12[PMID=14720526]

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103


eluting stent in diabetic patients

8.1 Available RCTs


A total of 6 RCTs which randomized 1188 patients were identified: all compared sirolimuseluting stent with paclitaxel eluting stent (see 8.1 page 104).

The average study size was 198 patients per arm (range 33 to 192 per arm). The first studywas published in 2005, and the last study was published in 2008.


Target lesion revascularisation data was reported in 5 trials; 2 trials reported data on MI(fatal and non fatal); 2 trials reported data on All cause death; 1 trials reported data onMACE; 1 trials reported data on CABG; 1 trials reported data on angiographic restenosis ; 3trials reported data on late stent thrombosis (31days - 1year); 1 trials reported data on Stentthrombosis (any, end of follow up); and 1 trials reported data on 4y stent thrombosis (ARC).

Following table 8.1 (page 104) summarized the main characteristics of the trials including inthis systematic review of RCTS of comparison versus paclitaxel eluting stent.


Table

8.1

:M

ain

study

chara

cter

isti

cs-

Dia

bet

icpat

ients

-co

mpar

ison

vers

us

pacl

itaxel

eluti

ng

sten

t

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

Tom

ai,

2008

[1]

n=

60

vs.

60

dia

bet

icpati

ent

wit

hm

ult

iple

de

nov

oco

ronary

art

ery

lesi

ons

siro

lim

us-

eluti

ng

sten

tvs.

pacl

itaxel

-elu

ting

sten

tN

AC

ross

over

Pri

mary

endp

oin

t:in

-ste

nt

late

lum

inal

loss

Sin

gle

cente

r,It

aly

Kim

,2008

[2]

n=

85

vs.

84

Kore

an

dia

bet

icpati

ents

wit

hhig

h-g

rade

de

nov

oco

ronary

lesi

ons

(ste

nosi

sof>

70

per

cent

of

the

lum

inal

dia

met

er)

requir

ing

<3

sten

ts

Cypher

vs.

Taxus

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:la

telu

men

loss

6ce

ntr

es,

Kore

a

RE

AL

ITY

(dia

bet

ics)

,2006

[3]

n=

187

vs.

192

SE

Svs.

PE

Sop

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:,

worl

dw

ide

SIR

TA

Xdia

bet

ics,

2005

[4,

5]

n=

108

vs.

93

Sub

gro

ups

of

dia

bet

ics

pati

ents

wit

hei

ther

stable

angin

aor

an

acu

teco

ronary

syndro

me

Cypher

vs.

Taxus

single

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:ca

rdia

cdea

th,

AM

I,T

LR

2ce

ntr

es,

Sw

itze

rland

ISA

R-D

IAB

ET

ES,

2005

[6]

n=

125

vs.

125

Dia

bet

icpati

ents

.A

Por

posi

tive

stre

ss,

no

AM

Iw

ith

clin

ically

signifi

cant

angio

gra

phic

sten

osi

sin

anati

ve

coro

nary

ves

sel

Taxus

vs.

Cypher

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:L

ate

lum

enlo

ss2

centr

es,

Ger

many

TA

xi

(dia

bet

ics)

,0

[]n

=33

vs.

36

SE

Svs.

PE

Sop

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:,

Sw

itze

rland





Data from 2 (among 6) trials evaluating all cause death were available. There was nostatistically significant difference in all cause death between sirolimus eluting stent and paclitaxeleluting stent, with a RR of 0.71 (95%CI 0.23 to 2.21, p=0.5568) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant. No heterogeneity across these trials was detected (p=0.7985, I2 = 0.00%).


Only one of the 6 studies eligible for this comparison provided data on MACE. No statisti-cally significant difference between the groups was found in MACE, with a RR of 1.64 (95% CI0.29 to 9.19, p=0.5759).

Data from 5 (among 6) trials evaluating target lesion revascularisation were available.When pooled together, there was no statistically significant difference between the groups intarget lesion revascularisation , with a RR of 0.72 (95% CI 0.40 to 1.29, p=0.2697). No hetero-geneity across these trials was detected (p =0.2287, I2 = 0.29%).


Only one of the 6 studies eligible for this comparison provided data on angiographicrestenosis . No statistically significant difference between the groups was found in angiographicrestenosis , with a RR of 0.40 (95% CI 0.08 to 1.98, p=0.2591).

Table 8.2: Results details - Diabetic patients - comparison versus paclitaxel eluting stent





MACE RR=1.64 [0.29;9.19] 0.5759 1.0000 (I=0.00) 1 69


CABG RR=0.99 [0.02;49.23] 0.9953 1.0000 (I=0.00) 1 169


RR=0.25 [0.01;5.49] 0.3791 1.0000 (I=0.00) 1 250



RR=0.41 [0.11;1.51] 0.1790 0.5890 (I=0.00) 3 830






Kim,2008 1/85 1/84 0.99 [0.06;15.54]

ISAR-DIABETES,2005 4/125 6/125 0.67 [0.19;2.31]

Global p ass= 0.5568 0.71 [0.23;2.21]







Kim,2008 1/85 1/84 0.99 [0.06;15.54]

ISAR-DIABETES,2005 5/125 3/125 1.67 [0.41;6.82]

Global p ass= 0.5297 1.50 [0.43;5.25]







TAxi (diabetics) 3/33 2/36 1.64 [0.29;9.19]

Global p ass= 0.5759 1.64 [0.29;9.19]







Kim,2008 2/85 4/84 0.49 [0.09;2.63]

REALITY (diabetics),2006 15/187 10/192 1.54 [0.71;3.34]

SIRTAX diabetics,2005 6/108 12/93 0.43 [0.17;1.10]

ISAR-DIABETES,2005 8/125 15/125 0.53 [0.23;1.21]

TAxi (diabetics) 1/33 1/36 1.09 [0.07;16.75]

Global p ass= 0.2697 0.72 [0.40;1.29]







Kim,2008 0/85 0/84 0.99 [0.02;49.23]

Global p ass= 0.9953 0.99 [0.02;49.23]






ISAR-DIABETES,2005 0/125 2/125 0.25 [0.01;5.49]

Global p ass= 0.3791 0.25 [0.01;5.49]







ISAR-DIABETES,2005 0/125 2/125 0.25 [0.01;5.49]

Global p ass= 0.3791 0.25 [0.01;5.49]






REALITY (diabetics),2006 2/187 6/192 0.34 [0.07;1.67]

SIRTAX diabetics,2005 0/108 2/93 0.22 [0.01;4.72]

ISAR-DIABETES,2005 1/125 0/125 2.00 [0.07;59.08]

Global p ass= 0.1790 0.41 [0.11;1.51]







Kim,2008 2/85 5/84 0.40 [0.08;1.98]

Global p ass= 0.2591 0.40 [0.08;1.98]



REFERENCES 109

References

[1] Tomai F, Reimers B, De Luca L, Galassi AR, Gaspardone A, Ghini AS, Ferrero V, Favero L, Gioffr G, PratiF, Tamburino C, Ribichini F, . Head-to-head comparison of sirolimus- and paclitaxel-eluting stent in thesame diabetic patient with multiple coronary artery lesions: a prospective, randomized, multicenter study..Diabetes Care 2008;31:15-9. [PMID=17909090]

[2] Kim MH, Hong SJ, Cha KS, Park HS, Chae SC, Hur SH, Gwon HC, Bae JH, Lim DS. Effect of Paclitaxel-eluting versus sirolimus-eluting stents on coronary restenosis in Korean diabetic patients.. J Interv Cardiol2008 Jun;21:225-31 [PMID=18341520]

[3] Windecker S.. Cypher is preferred in diabetics. 2006 Transcatheter Cardiovascular Therapeutics AnnualMeetings

[4] Togni M, Eber S, Widmer J, Billinger M, Wenaweser P, Cook S, Vogel R, Seiler C, Eberli FR, Maier W,Corti R, Roffi M, Lscher TF, Garachemani A, Hess OM, Wandel S, Meier B, Jni P, Windecker S. Impactof vessel size on outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents: a subgroupanalysis of the SIRTAX trial.. J Am Coll Cardiol 2007;50:1123-31 [PMID=17868802]

[5] Windecker S, Remondino A, Eberli FR, Jni P, Rber L, Wenaweser P, Togni M, Billinger M, Tller D, SeilerC, Roffi M, Corti R, Stsch G, Maier W, Lscher T, Hess OM, Egger M, Meier B. Sirolimus-eluting andpaclitaxel-eluting stents for coronary revascularization.. N Engl J Med 2005;353:653-62 [PMID=16105989]

[6] Dibra A, Kastrati A, Mehilli J, Pache J, Schhlen H, von Beckerath N, Ulm K, Wessely R, Dirschinger J,Schmig A. Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients.. N Engl JMed 2005;353:663-70 [PMID=16105990]

110CHAPTER 9. DETAILS FOR COMPARISON VERSUS RAPAMYCIN ELUTING STENT

9 Detailed results for comparison versus rapamycin

eluting stent in diabetic patients

9.1 Available RCTs

This section gives details for trials evaluating drug eluting stent comparison versus rapamycineluting stent

Only one trial which randomized 131 patients was identified: all compared paclitaxel elutingstent with rapamycin eluting stent (see 9.1 page 111).



data was reported in trials;Following table 9.1 (page 111) summarized the main characteristics of the trials including in

this systematic review of RCTS of comparison versus rapamycin eluting stent.


Table

9.1

:M

ain

study

chara

cter

isti

cs-

Dia

bet

icpat

ients

-co

mpar

ison

vers

us

rapam

yci

nel

uti

ng

sten

t

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Paclita

xelelu

ting

stentvers

us

rapam

ycin

elu

ting

stent

ISA

R-t

est

(dia

bet

ics)

,2006

[1]

n=

73

vs.

58

dia

bet

ics

pati

ents

wit

hde

nov

ole

sions

innati

ve

coro

nary

ves

sels

,ex

cludin

gth

ele

ftm

ain

trunk

Taxus

vs.

rapam

yci

nst

ent

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:,

ger

many

112 REFERENCES




No data were presented in the 1 trial identified

Table 9.2: Results details - Diabetic patients - comparison versus rapamycin eluting stent




References

[1] Mehilli J, Kastrati A, Wessely R, Dibra A, Hausleiter J, Jaschke B, Dirschinger J, Schmig A. Randomizedtrial of a nonpolymer-based rapamycin-eluting stent versus a polymer-based paclitaxel-eluting stent for thereduction of late lumen loss.. Circulation 2006;113:273-9 [PMID=16391155]

REFERENCES 113

10 Ongoing studies of Diabetic patients



Table 10.1: Ongoing studies for Diabetic patients

Study Description

PEPCAD IV (0)[] NCT00462631

Paclitaxel-eluting PTCA-balloon dilation (SeQuentTM Please) fol-lowed by cobalt-chromium stent (CoroflexTM Blue) deployment vs.Taxus Libert

patients with diabetes mellitus

DIABEDES IV (0)[] NCT00552994

Cypher select plus vs. Xience V

diabetic patients

FREEDOM (0)[] NCT00086450

TAXUS or CYPHER vs. CABG

diabetic individuals with multivessel coronary artery disease

Lipsia-Yukon-DM (0)[] NCT00368953

Yukon Choice stent system vs. Taxus Libert stent system

Patients With Diabetes Mellitus

References

114 REFERENCES

Part III

Acute myocardial infarction

115

117

11 Overview of available evidence for acute

myocardial infarction

A total of 10 RCTs which randomized 3337 patients were identified. (see tables 11.1 to 11.2 )In all, 8 reports concerned comparison versus bare-metal stent and 2 the comparison versus

paclitaxel eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 12 (page 129)

for comparison versus bare-metal stent and in section 13 (page 140 ) for comparison versuspaclitaxel eluting stent.


All trials were open-label in design. All included studies were reported in English language.We found one unpublished trial.

118CHAPTER 11. OVERVIEW OF AVAILABLE EVIDENCE FOR ACUTE MYOCARDIAL INFARCTION

Table

11.1

:M

ain

study

chara

cter

isti

cs-

Acu

tem

yoca

rdia

lin

farc

tion

-co

mpari

son

vers

us

bare

-met

alst

ent

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

bare

-meta

lst

ent

Dru

gelu

ting

stentvers

us

bare

-meta

lst

ent

DE

DIC

AT

ION

,2008

[1]

DE

Scu

rren

tly

use

dw

ith

or

wit

hout

dis

tal

pro

tect

ion

vs.

BM

Sw

ith

or

wit

hout

dis

tal

pro

tect

ion

313

vs.

313

op

enP

ara

llel

gro

ups

loss

of

the

lum

endia

met

erD

enm

ark

.

Paclita

xelelu

ting

stentvers

us

bare

-meta

lst

ent

HA

AM

U-S

TE

NT

,2006

[2]

Taxus

Expre

ssvs.

Bare

-met

al-

sten

t70

vs.

75

op

enP

ara

llel

gro

ups

none

Fin

land

PA

SSIO

N,

2006

[3]

Taxus

Expre

ss2

vs.

Expre

ss2

or

Lib

ert

310

vs.

309

op

enP

ara

llel

gro

ups

Com

bin

ati

on

of

card

iacd

eath

,A

MI,

TL

R

The

Net

her

lands

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

MIS

SIO

N,

2008

[4,

5]

Cypher

vs.

Vis

ion

158

vs.

152

single

-blind

Para

llel

gro

ups

inse

gm

ent

Late

lum

enlo

ssat

9m

o

the

Net

her

lands

Daz

de

laL

lera

,2007

[6]

siro

lim

us-

eluti

ng

sten

tsvs.

unco

ate

dst

ents

60

vs.

54

op

enP

ara

llel

gro

ups

card

iac

dea

th,

MI,

TL

RSpain

SE

SA

MI,

2007

[7]

Cypher

vs.

BX

sten

t,C

ord

is160

vs.

160

op

enP

ara

llel

gro

ups

Bin

ary

rest

enosi

sat

1y

Italy

TY

PH

OO

N,

2006

[8]

Cypher

or

Cypher

Sel

ect

vs.

any

com

mer

ciallyav

ailable

unco

ate

dst

ent

356

vs.

359

op

enP

ara

llel

gro

ups

Com

bin

ati

on

of

ves

selr

elate

d-

dea

th,

AM

I,T

VR

Worl

dw

ide

(15

countr

ies)

Pasc

eri,

2003

[9]

unpublish

edC

ypher

vs.

NA

vs.

NA

NA

Para

llel

gro

ups

NA

NA

119

Table

11.2

:M

ain

study

chara

cter

isti

cs-

Acu

tem

yoca

rdia

lin

farc

tion

-co

mpari

son

vers

us

pacl

itaxel

eluti

ng

sten

t

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

paclita

xel

elu

ting

stent

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

PR

OSIT

,2006

[1,

2,

3]

SE

SC

ord

isvs.

PE

SB

ost

on

Sci

enti

fic

154

vs.

154

op

enP

ara

llel

gro

ups

Late

lum

enlo

ssK

ore

a

Di

Lore

nzo

etal.,

2005

[4]

siro

lim

us

vs.

pacl

itaxel

90

vs.

90

op

enP

ara

llel

gro

ups

NA

NA


11.1 Main results for Acute myocardial infarction

The meta-analysis of the available trials provide the results listed in tables 11.3 to 11.4 (page120) and in the following graphs.


Drug eluting stent was superior to bare-metal stent in terms of MACE (RR=0.62, 95%CI 0.40 to 0.97, p=0.0366, 1 trial) and target-vessel revascularization (RR=0.39, 95% CI 0.22to 0.68, p=0.0000, 1 trial) .However, no significant difference was found on all cause death(RR=2.00, 95% CI 0.87 to 4.61, p=0.1034, 1 trial) and cardiac death (RR=2.60, 95% CI 0.94to 7.21, p=0.0662, 1 trial) .

No significant difference was found between paclitaxel eluting stent and bare-metalstent in terms of all cause death (RR=1.11, 95% CI 0.38 to 3.24, p=0.8550, 2 trials) , MI(fatal and non fatal) (RR=0.84, 95% CI 0.26 to 2.71, p=0.7654, 1 trial) and target lesionrevascularisation (RR=0.70, 95% CI 0.38 to 1.29, p=0.2540, 1 trial) .

Sirolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.48,95% CI 0.33 to 0.71, p=0.0000, 2 trials) , target-vessel revascularization (RR=0.40, 95% CI 0.28to 0.58, p=0.0000, 3 trials) , target lesion revascularisation (RR=0.36, 95% CI 0.18 to 0.71,p=0.0029, 2 trials) and angiographic restenosis (RR=0.23, 95% CI 0.06 to 0.93, p=0.0396, 2trials) with a random effect model in reason of a heterogeneity (Het. p=0.0441) .However, nosignificant difference was found on all cause death (RR=0.69, 95% CI 0.34 to 1.41, p=0.3077, 3trials) , cardiac death (RR=0.96, 95% CI 0.14 to 6.74, p=0.9689, 1 trial) , MI (fatal and nonfatal) (RR=0.68, 95% CI 0.33 to 1.40, p=0.2968, 2 trials) and CABG (RR=0.38, 95% CI 0.08to 1.95, p=0.2493, 1 trial) .


No significant difference was found between sirolimus eluting stent and paclitaxel elutingstent in terms of all cause death (RR=0.80, 95% CI 0.39 to 1.63, p=0.5391, 2 trials) , cardiacdeath (RR=0.56, 95% CI 0.17 to 1.87, p=0.3472, 1 trial) , MI (fatal and non fatal) (RR=1.16,95% CI 0.39 to 3.40, p=0.7909, 2 trials) , MACE (RR=0.50, 95% CI 0.23 to 1.08, p=0.0770, 1trial) and target lesion revascularisation (RR=0.66, 95% CI 0.30 to 1.43, p=0.2916, 2 trials) .



Drug eluting stent versus bare-metal stent


cardiac death RR=2.60 0.94;7.21 0.0662 1.0000 (0.00) 1 626

MACE RR=0.62 0.40;0.97 0.0366 1.0000 (1.00) 1 626



RR=0.88 0.32;2.38 0.7940 1.0000 (0.00) 1 626



continued...

11.3. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS121





RR=0.36 0.04;3.35 0.3676 1.0000 (1.00) 1 145



cardiac death RR=0.96 0.14;6.74 0.9689 1.0000 (0.00) 1 310


MACE RR=0.48 0.33;0.71 0.0000 0.5189 (0.00) 2 617



CABG RR=0.38 0.08;1.95 0.2493 1.0000 (0.00) 1 310


RR=0.94 0.47;1.84 0.8462 0.7574 (0.00) 3 1329



RR=0.96 0.14;6.74 0.9689 1.0000 (0.00) 1 310






cardiac death RR=0.56 0.17;1.87 0.3472 1.0000 (1.00) 1 305


MACE RR=0.50 0.23;1.08 0.0770 1.0000 (0.00) 1 308



RR=0.34 0.03;3.36 0.3576 0.7668 (0.00) 2 488



RR=0.50 0.02;14.80 0.6884 1.0000 (0.00) 1 308


RR=0.50 0.02;14.80 0.6884 1.0000 (0.00) 1 308


RR=1.00 0.02;50.08 1.0000 1.0000 (0.00) 1 308





Drug eluting stent versus bare-metalstent

2.00 [0.87;4.61] .10 1 626 1.00 0.00


1.11 [0.38;3.24] .86 2 750 .10 0.63


0.69 [0.34;1.41] .31 3 1329 .53 0.00



0.80 [0.39;1.63] .54 2 485 .92 0.00










2.60 [0.94;7.21] .07 1 626 1.00 0.00


0.96 [0.14;6.74] .97 1 310 1.00 0.00



0.56 [0.17;1.87] .35 1 305 1.00 1.00











0.84 [0.26;2.71] .77 1 605 1.00 0.00


0.68 [0.33;1.40] .30 2 617 .60 0.00



1.16 [0.39;3.40] .79 2 485 .78 0.00










0.62 [0.40;0.97] .04 1 626 1.00 1.00


0.48 [0.33;0.71] .00 2 617 .52 0.00



0.50 [0.23;1.08] .08 1 308 1.00 0.00











0.39 [0.22;0.68] .00 1 626 1.00 0.00


0.40 [0.28;0.58] .00 3 1329 .93 0.00


1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.7 0.80.91.0Relative risk









0.70 [0.38;1.29] .25 1 605 1.00 0.00


0.36 [0.18;0.71] .00 2 617 .79 0.00



0.66 [0.30;1.43] .29 2 485 .84 0.00











0.38 [0.08;1.95] .25 1 310 1.00 0.00











0.88 [0.32;2.38] .79 1 626 1.00 0.00


0.36 [0.04;3.35] .37 1 145 1.00 1.00


0.94 [0.47;1.84] .85 3 1329 .76 0.00



0.34 [0.03;3.36] .36 2 488 .77 0.00











1.46 [0.24;8.88] .68 2 617 .70 0.00



0.83 [0.15;4.48] .83 2 485 .74 0.00











0.50 [0.02;14.80] .69 1 308 1.00 0.00











0.96 [0.14;6.74] .97 1 310 1.00 0.00



0.50 [0.02;14.80] .69 1 308 1.00 0.00











1.00 [0.02;50.08] 1.00 1 308 1.00 0.00











0.23 [0.06;0.93] .04 2 476 .04 0.75


1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk





129


stent in acute myocardial infarction

12.1 Available RCTs


A total of 8 RCTs which randomized 2849 patients were identified: 1 trial compared drugeluting stent with bare-metal stent , 2 trials compared paclitaxel eluting stent with bare-metalstent and 5 trials compared sirolimus eluting stent with bare-metal stent (see 12.1 page 130).


All trials were open-label in design. All included studies were reported in English language.We found one unpublished trial.

All cause death data was reported in 6 trials; 4 trials reported data on target-vessel revas-cularization; 3 trials reported data on target lesion revascularisation ; 3 trials reported data onMI (fatal and non fatal); 3 trials reported data on MACE; 2 trials reported data on cardiacdeath; 2 trials reported data on angiographic restenosis ; 1 trials reported data on CABG; 5trials reported data on Stent thrombosis (any, end of follow up); 2 trials reported data on 4ystent thrombosis (ARC); and 1 trials reported data on sub acute stent thrombosis (1-30 days).

Following table 12.1 (page 130) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus bare-metal stent.


Table

12.1

:M

ain

study

chara

cter

isti

cs-

Acu

tem

yoca

rdia

lin

farc

tion

-co

mpari

son

vers

us

bare

-met

alst

ent

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Dru

gelu

ting

stentvers

us

bare

-meta

lst

ent

DE

DIC

AT

ION

,2008

[1]

n=

313

vs.

313

pati

ents

refe

rred

wit

hin

12

hours

from

sym

pto

monse

tof

an

ST

-ele

vati

on

myoca

rdia

lin

farc

tion

DE

Scu

rren

tly

use

dw

ith

or

wit

hout

dis

tal

pro

tect

ion

vs.

BM

Sw

ith

or

wit

hout

dis

tal

pro

tect

ion

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:lo

ssof

the

lum

endia

m-

eter

2ce

ntr

es,

Den

mark

.

Paclita

xelelu

ting

stentvers

us

bare

-meta

lst

ent

HA

AM

U-S

TE

NT

,2006

[2]

n=

70

vs.

75

AM

I-

ST

EM

Ipati

ents

under

goin

gP

CI

Taxus

Expre

ssvs.

Bare

-met

al-

sten

top

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:none

1ce

ntr

es,

Fin

land

PA

SSIO

N,

2006

[3]

n=

310

vs.

309

Myoca

rdia

lIn

farc

tion

wit

hST

-Seg

men

tE

leva

tion

Taxus

Expre

ss2

vs.

Expre

ss2

or

Lib

ert

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:C

om

bin

ati

on

of

car-

dia

cdea

th,

AM

I,T

LR

2ce

ntr

es,

The

Net

her

lands

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

MIS

SIO

N,

2008

[4,

5]

n=

158

vs.

152

pri

mary

per

cuta

neo

us

coro

nary

inte

rven

tion

for

ST

-seg

men

tel

evati

on

myoca

rdia

lin

farc

tion

(<9h)

Cypher

vs.

Vis

ion

single

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:in

segm

ent

Late

lum

enlo

ssat

9m

osi

ngle

-cen

ter,

the

Net

her

lands

Daz

de

laL

lera

,2007

[6]

n=

60

vs.

54

pri

mary

per

cuta

neo

us

coro

nary

inte

rven

tion

for

acu

tem

yoca

rdia

lin

farc

tion

wit

hST

-seg

men

tel

evati

on

siro

lim

us-

eluti

ng

sten

tsvs.

unco

ate

dst

ents

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:ca

rdia

cdea

th,

MI,

TL

R,

Spain

cont

inue

d...


Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

SE

SA

MI,

2007

[7]

n=

160

vs.

160

AM

IC

ypher

vs.

BX

sten

t,C

ord

isop

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:B

inary

rest

enosi

sat

1y

1ce

ntr

es,

Italy

TY

PH

OO

N,

2006

[8]

n=

356

vs.

359

AM

IC

ypher

or

Cypher

Sel

ect

vs.

any

com

mer

ciallyav

ailable

unco

ate

dst

ent

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:C

om

bin

ati

on

of

ves

sel-

rela

teddea

th,

AM

I,T

VR

48

centr

es,

Worl

dw

ide

(15

countr

ies)

Pasc

eri,

2003

[9]

unpublish

edn

=N

Avs.

NA

Cypher

vs.

Para

llel

gro

ups

Pri

mary

endp

oin

t:,





The single study eligible for this comparison provided data on all cause death. There wasno statistically significant difference in all cause death between drug eluting stent and bare-metal stent, with a RR of 2.00 (95%CI 0.87 to 4.61, p=0.1034) in favour of bare-metal stent. Inother words, all cause death was slightly lower in the bare-metal stent group , but this was notstatistically significant.


The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of drug eluting stent in MACE, with a RR of 0.62(95% CI 0.40 to 0.97, p=0.0366).

The single study eligible for this comparison provided data on target-vessel revascular-ization. The analysis detected a statistically significant difference in favor of drug eluting stentin target-vessel revascularization, with a RR of 0.39 (95% CI 0.22 to 0.68, p=0.0000).


All the 2 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between paclitaxeleluting stent and bare-metal stent, with a RR of 1.11 (95%CI 0.38 to 3.24, p=0.8550) in favourof bare-metal stent. In other words, all cause death was slightly lower in the bare-metal stentgroup , but this was not statistically significant. No heterogeneity across these trials was detected(p =0.1008, I2 = 0.63%).

Only one of the 2 studies eligible for this comparison provided data on MI (fatal and nonfatal). No statistically significant difference between the groups was found in MI (fatal and nonfatal), with a RR of 0.84 (95% CI 0.26 to 2.71, p=0.7654).

Only one of the 2 studies eligible for this comparison provided data on target lesion revas-cularisation . No statistically significant difference between the groups was found in targetlesion revascularisation , with a RR of 0.70 (95% CI 0.38 to 1.29, p=0.2540).


Data from 3 (among 5) trials evaluating all cause death were available. There was nostatistically significant difference in all cause death between sirolimus eluting stent and bare-metal stent, with a RR of 0.69 (95%CI 0.34 to 1.41, p=0.3077) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant. No heterogeneity across these trials was detected (p=0.5325, I2 = 0.00%).

Only one of the 5 studies eligible for this comparison provided data on cardiac death. Nostatistically significant difference between the groups was found in cardiac death, with a RR of0.96 (95% CI 0.14 to 6.74, p=0.9689).


Data from 2 (among 5) trials evaluating MACE were available. The analysis detected astatistically significant difference in favor of sirolimus eluting stent in MACE, with a RR of 0.48


(95% CI 0.33 to 0.71, p=0.0000). No heterogeneity across these trials was detected (p =0.5189,I2 = 0.00%).

Data from 3 (among 5) trials evaluating target-vessel revascularization were available.The analysis detected a statistically significant difference in favor of sirolimus eluting stentin target-vessel revascularization, with a RR of 0.40 (95% CI 0.28 to 0.58, p=0.0000). Noheterogeneity across these trials was detected (p =0.9306, I2 = 0.00%).



Data from 2 (among 5) trials evaluating angiographic restenosis were available. Theanalysis detected a statistically significant difference in favor of sirolimus eluting stent in angio-graphic restenosis , with a RR of 0.23 (95% CI 0.06 to 0.93, p=0.0396). A random effect modelwas used because there was a substantial statistical heterogeneity detected between the studies(p =0.0441, I2 = 0.75%).

Table 12.2: Results details - Acute myocardial infarction - comparison versus bare-metal stent





MACE RR=0.62 [0.40;0.97] 0.0366 1.0000 (I=1.00) 1 626



RR=0.88 [0.32;2.38] 0.7940 1.0000 (I=0.00) 1 626






RR=0.36 [0.04;3.35] 0.3676 1.0000 (I=1.00) 1 145





MACE RR=0.48 [0.33;0.71] 0.0000 0.5189 (I=0.00) 2 617



CABG RR=0.38 [0.08;1.95] 0.2493 1.0000 (I=0.00) 1 310


RR=0.94 [0.47;1.84] 0.8462 0.7574 (I=0.00) 3 1329



RR=0.96 [0.14;6.74] 0.9689 1.0000 (I=0.00) 1 310






DEDICATION,2008 16/313 8/313 2.00 [0.87;4.61]

Global p ass= 0.1034 2.00 [0.87;4.61]


HAAMU-STENT,2006 8/70 4/75 2.14 [0.67;6.80]

PASSION,2006 14/302 20/303 0.70 [0.36;1.36]

Global p ass= 0.8550 1.11 [0.38;3.24]



MISSION,2008 2/158 4/152 0.48 [0.09;2.59]

SESAMI,2007 3/154 7/153 0.43 [0.11;1.62]

TYPHOON,2006 8/355 8/357 1.01 [0.38;2.65]

Global p ass= 0.3077 0.69 [0.34;1.41]







DEDICATION,2008 13/313 5/313 2.60 [0.94;7.21]

Global p ass= 0.0662 2.60 [0.94;7.21]


MISSION,2008 2/158 2/152 0.96 [0.14;6.74]

Global p ass= 0.9689 0.96 [0.14;6.74]







PASSION,2006 5/302 6/303 0.84 [0.26;2.71]

Global p ass= 0.7654 0.84 [0.26;2.71]


MISSION,2008 9/158 14/152 0.62 [0.28;1.39]

SESAMI,2007 3/154 3/153 0.99 [0.20;4.85]

Global p ass= 0.2968 0.68 [0.33;1.40]







DEDICATION,2008 28/313 45/313 0.62 [0.40;0.97]

Global p ass= 0.0366 0.62 [0.40;0.97]


MISSION,2008 22/158 40/152 0.53 [0.33;0.85]

SESAMI,2007 11/154 27/153 0.40 [0.21;0.79]

Global p ass= 0.0000 0.48 [0.33;0.71]


1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk






DEDICATION,2008 16/313 41/313 0.39 [0.22;0.68]

Global p ass= 0.0000 0.39 [0.22;0.68]


MISSION,2008 8/158 20/152 0.38 [0.17;0.85]

SESAMI,2007 8/154 22/153 0.36 [0.17;0.79]

TYPHOON,2006 20/355 47/357 0.43 [0.26;0.71]

Global p ass= 0.0000 0.40 [0.28;0.58]


1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk





PASSION,2006 16/302 23/303 0.70 [0.38;1.29]

Global p ass= 0.2540 0.70 [0.38;1.29]


MISSION,2008 4/158 12/152 0.32 [0.11;0.97]

SESAMI,2007 7/154 18/153 0.39 [0.17;0.90]

Global p ass= 0.0029 0.36 [0.18;0.71]








MISSION,2008 2/158 5/152 0.38 [0.08;1.95]

Global p ass= 0.2493 0.38 [0.08;1.95]






DEDICATION,2008 7/313 8/313 0.88 [0.32;2.38]

Global p ass= 0.7940 0.88 [0.32;2.38]


HAAMU-STENT,2006 1/70 3/75 0.36 [0.04;3.35]

Global p ass= 0.3676 0.36 [0.04;3.35]


MISSION,2008 2/158 3/152 0.64 [0.11;3.79]

SESAMI,2007 2/154 1/153 1.99 [0.18;21.69]

TYPHOON,2006 12/355 13/357 0.93 [0.43;2.01]

Global p ass= 0.8462 0.94 [0.47;1.84]








MISSION,2008 1/158 1/152 0.96 [0.06;15.24]

SESAMI,2007 2/154 1/153 1.99 [0.18;21.69]

Global p ass= 0.6834 1.46 [0.24;8.88]







MISSION,2008 2/158 2/152 0.96 [0.14;6.74]

Global p ass= 0.9689 0.96 [0.14;6.74]






MISSION,2008 3/158 28/152 0.10 [0.03;0.33]

SESAMI,2007 8/86 17/80 0.44 [0.20;0.96]




1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk


REFERENCES 139

References

[1] Kelbaek H, Thuesen L, Helqvist S, Clemmensen P, Klvgaard L, Kaltoft A, Andersen B, Thuesen H, EngstrmT, Btker HE, Saunamki K, Krusell LR, Jrgensen E, Hansen HH, Christiansen EH, Ravkilde J, Kber L, KofoedKF, Terkelsen CJ, Lassen JF. Drug-eluting versus bare metal stents in patients with st-segment-elevationmyocardial infarction: eight-month follow-up in the Drug Elution and Distal Protection in Acute MyocardialInfarction (DEDICATION) trial.. Circulation 2008 Sep 9;118:1155-62 [PMID=18725489]

[2] Tierala I, Syvaenne M, Kupari M. Randomised comparison of apaclitaxel-eluting and a bare metal stentin STEMI-PCI. TheHAAMU-STENT-study. Annual Scientifi c Meeting of theTranscatheter CardiovascularTherapeutics; Washington, DC;Oct 2227, 2006. Abstract 178.

[3] Laarman GJ, Suttorp MJ, Dirksen MT, van Heerebeek L, Kiemeneij F, Slagboom T, van der Wieken LR,Tijssen JG, Rensing BJ, Patterson M. Paclitaxel-eluting versus uncoated stents in primary percutaneouscoronary intervention.. N Engl J Med 2006;355:1105-13 [PMID=16971717]

[4] van der Hoeven BL, Liem S, Jukema JW, et al.. Prospectiverandomised trial to evaluate the effi cacyand safety of drug-elutingstents versus barem-metal stents for the treatment of acutemyocardial infarction(the MISSION! intervention study). AnnualScientifi c Meeting of the American Heart Association. Chicago,IL,USA; Nov 1215, 2006.

[5] van der Hoeven BL, Liem SS, Jukema JW, Suraphakdee N, Putter H, Dijkstra J, Atsma DE, Bootsma M,Zeppenfeld K, Oemrawsingh PV, van der Wall EE, Schalij MJ. Sirolimus-eluting stents versus bare-metalstents in patients with ST-segment elevation myocardial infarction: 9-month angiographic and intravascularultrasound results and 12-month clinical outcome results from the MISSION! Intervention Study.. J AmColl Cardiol 2008 Feb 12;51:618-26 [PMID=18261680]

[6] Daz de la Llera LS, Ballesteros S, Nevado J, Fernndez M, Villa M, Snchez A, Retegui G, Garca D, Mart-nez A. Sirolimus-eluting stents compared with standard stents in the treatment of patients with primaryangioplasty.. Am Heart J 2007;154:164.e1-6 [PMID=17584571]

[7] Menichelli M, Parma A, Pucci E, Fiorilli R, De Felice F, Nazzaro M, Giulivi A, Alborino D, AzzellinoA, Violini R. Randomized trial of Sirolimus-Eluting Stent Versus Bare-Metal Stent in Acute MyocardialInfarction (SESAMI).. J Am Coll Cardiol 2007;49:1924-30 [PMID=17498576]

[8] Spaulding C, Henry P, Teiger E, Beatt K, Bramucci E, Carri D, Slama MS, Merkely B, Erglis A, MargheriM, Varenne O, Cebrian A, Stoll HP, Snead DB, Bode C. Sirolimus-eluting versus uncoated stents in acutemyocardial infarction.. N Engl J Med 2006;355:1093-104 [PMID=16971716]

[9] Pasceri V, Granatelli A, Pristipino C, et al.. A randomized trial of arapamycin-eluting stent in acute my-ocardial infarction: preliminaryresults. TCT 2003. Am J Cardiol 2003;92(Suppl 6A):1L.



eluting stent in acute myocardial infarction

13.1 Available RCTs





Target lesion revascularisation data was reported in 2 trials; 2 trials reported data on MI(fatal and non fatal); 2 trials reported data on All cause death; 1 trials reported data on MACE;1 trials reported data on cardiac death; 2 trials reported data on Stent thrombosis (any, endof follow up); 2 trials reported data on 4y stent thrombosis (ARC); 1 trials reported data onsub acute stent thrombosis (1-30 days); 1 trials reported data on late stent thrombosis (31days- 1year); and 1 trials reported data on Acute stent thrombosis (¡=24h).

Following table 13.1 (page 141) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus paclitaxel eluting stent.


Table

13.1

:M

ain

study

char

act

eris

tics

-A

cute

myo

card

ialin

farc

tion

-co

mpar

ison

vers

us

pacl

itaxel

eluti

ng

sten

t

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

PR

OSIT

,2006

[1,

2,

3]

n=

154

vs.

154

AM

Ior

per

sist

ent

isch

aem

ia12-2

4h

SE

SC

ord

isvs.

PE

SB

ost

on

Sci

enti

fic

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:L

ate

lum

enlo

ss3

centr

es,

Kore

a

Di

Lore

nzo

etal.,

2005

[4]

n=

90

vs.

90

ST

-seg

men

tel

evati

on

myoca

rdia

lin

farc

tion

siro

lim

us

vs.

pacl

itaxel

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:N

A,

NA








Only one of the 2 studies eligible for this comparison provided data on MACE. No statisti-cally significant difference between the groups was found in MACE, with a RR of 0.50 (95% CI0.23 to 1.08, p=0.0770).

All the 2 studies had extractable data about the number of participants with target lesionrevascularisation . When pooled together, there was no statistically significant differencebetween the groups in target lesion revascularisation , with a RR of 0.66 (95% CI 0.30 to 1.43,p=0.2916). No heterogeneity across these trials was detected (p =0.8352, I2 = 0.00%).

Table 13.2: Results details - Acute myocardial infarction - comparison versus paclitaxel elutingstent






MACE RR=0.50 [0.23;1.08] 0.0770 1.0000 (I=0.00) 1 308



RR=0.34 [0.03;3.36] 0.3576 0.7668 (I=0.00) 2 488



RR=0.50 [0.02;14.80] 0.6884 1.0000 (I=0.00) 1 308


RR=0.50 [0.02;14.80] 0.6884 1.0000 (I=0.00) 1 308


RR=1.00 [0.02;50.08] 1.0000 1.0000 (I=0.00) 1 308





PROSIT,2006 10/154 12/151 0.82 [0.36;1.83]

Di Lorenzo et al.,2005 3/90 4/90 0.75 [0.17;3.26]

Global p ass= 0.5391 0.80 [0.39;1.63]







PROSIT,2006 4/154 7/151 0.56 [0.17;1.87]

Global p ass= 0.3472 0.56 [0.17;1.87]






PROSIT,2006 3/154 3/151 0.98 [0.20;4.78]

Di Lorenzo et al.,2005 4/90 3/90 1.33 [0.31;5.79]

Global p ass= 0.7909 1.16 [0.39;3.40]








PROSIT,2006 9/154 18/154 0.50 [0.23;1.08]

Global p ass= 0.0770 0.50 [0.23;1.08]






PROSIT,2006 7/154 11/151 0.62 [0.25;1.57]

Di Lorenzo et al.,2005 3/90 4/90 0.75 [0.17;3.26]

Global p ass= 0.2916 0.66 [0.30;1.43]







PROSIT,2006 0/154 2/154 0.25 [0.01;5.50]

Di Lorenzo et al.,2005 0/90 1/90 0.50 [0.02;14.72]

Global p ass= 0.3576 0.34 [0.03;3.36]








PROSIT,2006 2/154 2/151 0.98 [0.14;6.87]

Di Lorenzo et al.,2005 0/90 1/90 0.50 [0.02;14.72]

Global p ass= 0.8278 0.83 [0.15;4.48]







PROSIT,2006 0/154 1/154 0.50 [0.02;14.80]

Global p ass= 0.6884 0.50 [0.02;14.80]






PROSIT,2006 0/154 1/154 0.50 [0.02;14.80]

Global p ass= 0.6884 0.50 [0.02;14.80]



146 REFERENCES




PROSIT,2006 0/154 0/154 1.00 [0.02;50.08]

Global p ass= 1.0000 1.00 [0.02;50.08]



References

[1] Lee JH, Kim HS, Lee SW, et al.. Prospective randomized trial of asirolimus eluting versus a paclitaxeleluting stent for the treatmentof acute ST-elevation myocardial infarction. Annual Scientifi cMeeting of theAmerican College of Cardiology; Atlanta, GA, USA;March 1114, 2006.

[2] Kornowski R. Drug-eluting stents in ST elevation myocardial infarction: In light of the PROSIT trial..Catheter Cardiovasc Interv 2008 Jul 1;72:33-5 [PMID=18561153]

[3] Lee JH, Kim HS, Lee SW, Park JH, Choi SW, Jeong JO, Cho Y, Lee N, Rhee KS, Ko JK, SeongIW. Prospective randomized comparison of sirolimus- versus paclitaxel-eluting stents for the treatmentof acute ST-elevation myocardial infarction: pROSIT trial.. Catheter Cardiovasc Interv 2008 Jul 1;72:25-32[PMID=18412270]

[4] Di Lorenzo E, Varricchio A, Lanzillo T, et al.. Paclitaxel and sirolimusstent implantation in patients withacute myocardial infarction (abstr). Circulation 2005;112:U538

REFERENCES 147

14 Ongoing studies of Acute myocardial infarction


Only one study was still ongoing at the date of this report. A list of these ongoing studies witha brief description is given table 14.1.

Table 14.1: Ongoing studies for Acute myocardial infarction

Study Description

ZEST AMI (0)[] NCT00422565

Endeavor (ABT 578-eluting balloon expandable stent, Medtronic) vs.Cypher or Taxus Libert

Acute Myocardial Infarction Patients

References

148 REFERENCES

Part IV

Small vessels

149

151

15 Overview of available evidence for small vessels

A total of 3 RCTs which randomized 1112 patients were identified. (see tables 15.1 to 15.2 )In all, 1 report concerned comparison versus bare-metal stent and 2 the comparison versus

paclitaxel eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 16 (page 160)

for comparison versus bare-metal stent and in section 17 (page 166 ) for comparison versuspaclitaxel eluting stent.


Erreur ??? 0 et 0.All included studies were reported in English language. We did not found any unpublished

trial.

152 CHAPTER 15. OVERVIEW OF AVAILABLE EVIDENCE FOR SMALL VESSELS

Table

15.1

:M

ain

study

char

acte

rist

ics

-sm

allve

ssel

s-

com

par

ison

ver

sus

bare

-met

alst

ent

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

bare

-meta

lst

ent

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

SE

S-S

MA

RT

,2004

[1]

Cypher

vs.

Bx

Sonic

129

vs.

128

single

-blind

Para

llel

gro

ups

Bin

ary

rest

enosi

sIt

alian

153

Table

15.2

:M

ain

study

char

acte

rist

ics

-sm

allve

ssel

s-

com

par

ison

ver

sus

pacl

itaxel

eluti

ng

sten

t

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

paclita

xel

elu

ting

stent

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

ISA

R-S

MA

RT

3,

2006

[1]

Taxus

vs.

Cypher

180

vs.

180

NA

Para

llel

gro

ups

Late

lum

enlo

ssG

erm

any

SIR

TA

X(s

mall

ves

sels

subgro

up),

2005

[2]

Cypher

vs.

Taxus

249

vs.

246

single

-blind

Para

llel

gro

ups

card

iac

dea

th,

AM

I,T

LR

Sw

itze

rland


15.1 Main results for small vessels



Sirolimus eluting stent was superior to bare-metal stent in terms of MI (fatal and non fatal)(RR=0.20, 95% CI 0.04 to 0.89, p=0.0344, 1 trial) , MACE (RR=0.30, 95% CI 0.16 to 0.54,p=0.0000, 1 trial) , target lesion revascularisation (RR=0.33, 95% CI 0.16 to 0.68, p=0.0024, 1trial) and angiographic restenosis (RR=0.18, 95% CI 0.10 to 0.32, p=0.0000, 1 trial) .However,no significant difference was found on all cause death (RR=0.25, 95% CI 0.01 to 5.45, p=0.3765,1 trial) and CABG (RR=0.25, 95% CI 0.01 to 5.45, p=0.3765, 1 trial) .


Sirolimus eluting stent was superior to paclitaxel eluting stent in terms of MACE (RR=0.49,95% CI 0.29 to 0.81, p=0.0052, 1 trial) , target-vessel revascularization (RR=0.40, 95% CI0.22 to 0.71, p=0.0019, 1 trial) and target lesion revascularisation (RR=0.47, 95% CI 0.27to 0.82, p=0.0084, 2 trials) .However, no significant difference was found on all cause death(RR=0.92, 95% CI 0.52 to 1.64, p=0.7840, 2 trials) , cardiac death (RR=0.64, 95% CI 0.21 to1.92, p=0.4238, 1 trial) , MI (fatal and non fatal) (RR=1.23, 95% CI 0.61 to 2.46, p=0.5662, 2trials) and CABG (RR=0.20, 95% CI 0.02 to 1.73, p=0.1454, 1 trial) .






MACE RR=0.30 0.16;0.54 0.0000 1.0000 (0.00) 1 257


CABG RR=0.25 0.01;5.45 0.3765 1.0000 (0.00) 1 257


RR=0.25 0.03;2.19 0.2096 1.0000 (0.00) 1 257






cardiac death RR=0.64 0.21;1.92 0.4238 1.0000 (0.00) 1 370


MACE RR=0.49 0.29;0.81 0.0052 1.0000 (0.00) 1 370



continued...



CABG RR=0.20 0.02;1.73 0.1454 1.0000 (0.00) 1 370


RR=0.85 0.26;2.75 0.7832 0.8971 (0.00) 2 730






0.25 [0.01;5.45] .38 1 257 1.00 0.00



0.92 [0.52;1.64] .78 2 730 .52 0.00











0.64 [0.21;1.92] .42 1 370 1.00 0.00











0.20 [0.04;0.89] .03 1 257 1.00 0.00



1.23 [0.61;2.46] .57 2 730 .64 0.00










0.30 [0.16;0.54] .00 1 257 1.00 0.00



0.49 [0.29;0.81] .01 1 370 1.00 0.00

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk











0.40 [0.22;0.71] .00 1 370 1.00 0.00

1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.7 0.80.91.0Relative risk









0.33 [0.16;0.68] .00 1 257 1.00 0.00



0.47 [0.27;0.82] .01 2 730 .17 0.46

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk










0.25 [0.01;5.45] .38 1 257 1.00 0.00



0.20 [0.02;1.73] .15 1 370 1.00 0.00










0.25 [0.03;2.19] .21 1 257 1.00 0.00



0.85 [0.26;2.75] .78 2 730 .90 0.00












1.00 [0.06;15.87] 1.00 1 360 1.00 0.00










0.18 [0.10;0.32] .00 1 236 1.00 0.00


1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk







stent in small vessels

16.1 Available RCTs


Only one trial which randomized 257 patients was identified: all compared sirolimus elutingstent with bare-metal stent (see 16.1 page 161).



trial.Target lesion revascularisation data was reported in 1 trials; 1 trials reported data on MI

(fatal and non fatal); 1 trials reported data on MACE; 1 trials reported data on CABG; 1 trialsreported data on angiographic restenosis ; 1 trials reported data on All cause death; and 1 trialsreported data on Stent thrombosis (any, end of follow up).



Table

16.1

:M

ain

study

char

acte

rist

ics

-sm

allve

ssel

s-

com

par

ison

ver

sus

bare

-met

alst

ent

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

SE

S-S

MA

RT

,2004

[1]

n=

129

vs.

128

Sta

ble

AP

,A

CS,

sile

nt

myoca

rdia

lis

chaem

iaas

show

nby

exer

cise

stre

sste

stC

ypher

vs.

Bx

Sonic

single

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:B

inary

rest

enosi

s20

centr

es,

Italian





The single study eligible for this comparison provided data on all cause death. There wasno statistically significant difference in all cause death between sirolimus eluting stent and bare-metal stent, with a RR of 0.25 (95%CI 0.01 to 5.45, p=0.3765) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant.

The single study eligible for this comparison provided data on MI (fatal and non fatal).The analysis detected a statistically significant difference in favor of sirolimus eluting stent inMI (fatal and non fatal), with a RR of 0.20 (95% CI 0.04 to 0.89, p=0.0344).

The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of sirolimus eluting stent in MACE, with a RR of0.30 (95% CI 0.16 to 0.54, p=0.0000).

The single study eligible for this comparison provided data on target lesion revasculari-sation . The analysis detected a statistically significant difference in favor of sirolimus elutingstent in target lesion revascularisation , with a RR of 0.33 (95% CI 0.16 to 0.68, p=0.0024).

The single study eligible for this comparison provided data on CABG. No statisticallysignificant difference between the groups was found in CABG, with a RR of 0.25 (95% CI 0.01to 5.45, p=0.3765).


Table 16.2: Results details - small vessels - comparison versus bare-metal stent





MACE RR=0.30 [0.16;0.54] 0.0000 1.0000 (I=0.00) 1 257


CABG RR=0.25 [0.01;5.45] 0.3765 1.0000 (I=0.00) 1 257


RR=0.25 [0.03;2.19] 0.2096 1.0000 (I=0.00) 1 257






SES-SMART,2004 0/129 2/128 0.25 [0.01;5.45]

Global p ass= 0.3765 0.25 [0.01;5.45]






SES-SMART,2004 2/129 10/128 0.20 [0.04;0.89]

Global p ass= 0.0344 0.20 [0.04;0.89]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk





SES-SMART,2004 12/129 40/128 0.30 [0.16;0.54]

Global p ass= 0.0000 0.30 [0.16;0.54]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk






SES-SMART,2004 9/129 27/128 0.33 [0.16;0.68]

Global p ass= 0.0024 0.33 [0.16;0.68]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk





SES-SMART,2004 0/129 2/128 0.25 [0.01;5.45]

Global p ass= 0.3765 0.25 [0.01;5.45]






SES-SMART,2004 1/129 4/128 0.25 [0.03;2.19]

Global p ass= 0.2096 0.25 [0.03;2.19]



REFERENCES 165




SES-SMART,2004 12/123 60/113 0.18 [0.10;0.32]

Global p ass= 0.0000 0.18 [0.10;0.32]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk


References

[1] Ardissino D, Cavallini C, Bramucci E, Indolfi C, Marzocchi A, Manari A, Angeloni G, Carosio G, BonizzoniE, Colusso S, Repetto M, Merlini PA. Sirolimus-eluting vs uncoated stents for prevention of restenosis insmall coronary arteries: a randomized trial.. JAMA 2004;292:2727-34 [PMID=15585732]



eluting stent in small vessels

17.1 Available RCTs





trial.Target lesion revascularisation data was reported in 2 trials; 2 trials reported data on MI

(fatal and non fatal); 2 trials reported data on All cause death; 1 trials reported data on target-vessel revascularization; 1 trials reported data on MACE; 1 trials reported data on cardiac death;1 trials reported data on CABG; 2 trials reported data on Stent thrombosis (any, end of followup); and 1 trials reported data on 4y stent thrombosis (ARC).



Table

17.1

:M

ain

study

char

acte

rist

ics

-sm

allve

ssel

s-

com

par

ison

ver

sus

pacl

itaxel

eluti

ng

sten

t

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

ISA

R-S

MA

RT

3,

2006

[1]

n=

180

vs.

180

Sm

all

ves

sels

,de

nov

ole

sions

innati

ve

coro

nary

ves

sels

wit

ha

dia

met

erof<

2.8

0m

mnondia

bet

icpati

ents

.A

Por

posi

tive

stre

ss,

no

AM

I

Taxus

vs.

Cypher

NA

Para

llel

gro

ups

Pri

mary

endp

oin

t:L

ate

lum

enlo

ss2

centr

es,

Ger

many

SIR

TA

X(s

mall

ves

sels

subgro

up),

2005

[2]

n=

249

vs.

246

Unse

lect

edpati

ents

.Sta

ble

AP

,A

CS,

incl

udin

gA

MI.

at

least

one

lesi

on

wit

hst

enosi

sof

at

least

50

per

cent

ina

ves

sel

wit

ha

refe

rence

dia

met

erb

etw

een

2.2

5and

4.0

0m

mth

at

was

suit

able

for

sten

tim

pla

nta

tion

Cypher

vs.

Taxus

single

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:ca

rdia

cdea

th,

AM

I,T

LR

2ce

ntr

es,

Sw

itze

rland








Only one of the 2 studies eligible for this comparison provided data on MACE. The analysisdetected a statistically significant difference in favor of sirolimus eluting stent in MACE, with aRR of 0.49 (95% CI 0.29 to 0.81, p=0.0052).


All the 2 studies had extractable data about the number of participants with target le-sion revascularisation . The analysis detected a statistically significant difference in favor ofsirolimus eluting stent in target lesion revascularisation , with a RR of 0.47 (95% CI 0.27 to0.82, p=0.0084). No heterogeneity across these trials was detected (p =0.1739, I2 = 0.46%).


Table 17.2: Results details - small vessels - comparison versus paclitaxel eluting stent






MACE RR=0.49 [0.29;0.81] 0.0052 1.0000 (I=0.00) 1 370



CABG RR=0.20 [0.02;1.73] 0.1454 1.0000 (I=0.00) 1 370


RR=0.85 [0.26;2.75] 0.7832 0.8971 (I=0.00) 2 730






ISAR-SMART 3,2006 10/180 13/180 0.77 [0.35;1.71]

SIRTAX (small vessels sub 11/183 10/187 1.12 [0.49;2.58]

Global p ass= 0.7840 0.92 [0.52;1.64]








Global p ass= 0.4238 0.64 [0.21;1.92]






ISAR-SMART 3,2006 10/180 7/180 1.43 [0.56;3.67]


Global p ass= 0.5662 1.23 [0.61;2.46]









Global p ass= 0.0052 0.49 [0.29;0.81]

1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk






Global p ass= 0.0019 0.40 [0.22;0.71]

1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk





ISAR-SMART 3,2006 20/180 33/180 0.61 [0.36;1.01]


Global p ass= 0.0084 0.47 [0.27;0.82]









Global p ass= 0.1454 0.20 [0.02;1.73]






ISAR-SMART 3,2006 1/180 1/180 1.00 [0.06;15.87]


Global p ass= 0.7832 0.85 [0.26;2.75]







ISAR-SMART 3,2006 1/180 1/180 1.00 [0.06;15.87]

Global p ass= 1.0000 1.00 [0.06;15.87]



172 REFERENCES

References

[1] Mehilli J, Dibra A, Kastrati A, Pache J, Dirschinger J, Schmig A. Randomized trial of paclitaxel- andsirolimus-eluting stents in small coronary vessels.. Eur Heart J 2006;27:260-6 [PMID=16401670]

[2] Togni M, Eber S, Widmer J, Billinger M, Wenaweser P, Cook S, Vogel R, Seiler C, Eberli FR, Maier W,Corti R, Roffi M, Lscher TF, Garachemani A, Hess OM, Wandel S, Meier B, Jni P, Windecker S. Impactof vessel size on outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents: a subgroupanalysis of the SIRTAX trial.. J Am Coll Cardiol 2007;50:1123-31 [PMID=17868802]

REFERENCES 173

18 Ongoing studies of small vessels


No ongoing trial was identified. still ongoing at the date of this report. A list of these ongoingstudies with a brief description is given table 18.1.

Table 18.1: Ongoing studies for small vessels

Study Description

References

174 REFERENCES

Part V

Long or complex lesion

175

177

19 Overview of available evidence for long or

complex lesion


CABG and 5 the comparison versus paclitaxel eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 20 (page 189)

for comparison versus bare-metal stent, in section 21 (page 197 ) for comparison versus CABGand in section 22 (page 202 ) for comparison versus paclitaxel eluting stent.


178CHAPTER 19. OVERVIEW OF AVAILABLE EVIDENCE FOR LONG OR COMPLEX LESION

Table

19.1

:M

ain

study

char

act

eris

tics

-lo

ng

orco

mple

xle

sion

-co

mpar

ison

ver

sus

bare

-met

alst

ent

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

bare

-meta

lst

ent

Paclita

xelelu

ting

stentvers

us

bare

-meta

lst

ent

TA

XU

SV

I,2005

[1,

2]

TA

XU

Svs.

Expre

ss2

sten

t219

vs.

227

double

-blind

Para

llel

gro

ups

TV

RE

uro

pe

TA

XU

SV

(all

pati

ents

),2005

[3]

TA

XU

Svs.

bare

met

al

EX

PR

ESS-2

577

vs.

579

double

-blind

Para

llel

gro

ups

TV

RU

nit

edSta

tes

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

SC

AN

DST

EN

T,

2006

[4,

5]

Cypher

vs.

Sonic

163

vs.

159

op

enP

ara

llel

gro

ups

Min

imal

lum

endia

met

erD

enm

ark

179

Table

19.2

:M

ain

study

char

acte

rist

ics

-lo

ng

orco

mple

xle

sion

-co

mpar

ison

vers

us

CA

BG

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

CA

BG

Paclita

xelelu

ting

stentvers

us

CA

BG

SY

NT

AX

,0

[]unpublish

edpacl

itaxel

(taxus

Expre

ssSR

)vs.

Coro

nary

Art

ery

Bypass

Surg

ery

903

vs.

897

op

enP

ara

llel

gro

ups

MA

CE

NA


Table

19.3

:M

ain

study

char

act

eris

tics

-lo

ng

orco

mple

xle

sion

-co

mpar

ison

ver

sus

pacl

itaxel

eluti

ng

sten

t

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

paclita

xel

elu

ting

stent

Genous

stentvers

us

paclita

xelelu

ting

stent

TR

IAS-H

R,

2008

[]G

enous

sten

t(a

nti

body-c

oate

dbare

-met

al

sten

t)fo

llow

edby

one

month

of

dual

anti

pla

tele

tth

erapy

vs.

Taxus

or

Cypher

follow

edby

at

least

six

month

sof

dual

anti

pla

tele

tth

erapy

98

vs.

95

single

-blind

Para

llel

gro

ups

targ

etle

sion

failure

NA

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

Pet

ronio

etal,

2007

[1]

Cypher

vs.

Taxus

50

vs.

50

op

enP

ara

llel

gro

ups

Neo

inti

mal

hyp

erpla

sia

Italy

Cer

vin

ka,

2006

[2]

siro

lim

us-

eluti

ng

sten

tvs.

pacl

itaxel

-elu

ting

sten

t

37

vs.

33

op

enP

ara

llel

gro

ups

Neo

inti

mal

hyp

erpla

sia

NA

LO

NG

DE

SII

,2006

[3]

SE

Svs.

PE

S250

vs.

250

single

-blind

Para

llel

gro

ups

Bin

ary

rest

enosi

sK

ore

a

CO

RP

AL

,2005

[4]

siro

lim

us

vs.

pacl

itaxel

331

vs.

321

op

enP

ara

llel

gro

ups

Bin

ary

rest

enosi

sSpain

19.1. MAIN RESULTS FOR LONG OR COMPLEX LESION 181

19.1 Main results for long or complex lesion



Paclitaxel eluting stent was superior to bare-metal stent in terms of MACE (RR=0.71,95% CI 0.58 to 0.88, p=0.0016, 2 trials) , target-vessel revascularization (RR=0.70, 95% CI0.53 to 0.93, p=0.0145, 1 trial) , target lesion revascularisation (RR=0.55, 95% CI 0.39 to 0.77,p=0.0000, 1 trial) and angiographic restenosis (RR=0.43, 95% CI 0.33 to 0.56, p=0.0000, 1 trial).However, no significant difference was found on all cause death (RR=0.79, 95% CI 0.30 to 2.07,p=0.6308, 2 trials) and MI (fatal and non fatal) (RR=1.16, 95% CI 0.71 to 1.88, p=0.5584, 2trials) .

Sirolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.10,95% CI 0.04 to 0.25, p=0.0000, 1 trial) , target lesion revascularisation (RR=0.08, 95% CI0.03 to 0.23, p=0.0000, 1 trial) and angiographic restenosis (RR=0.06, 95% CI 0.02 to 0.18,p=0.0000, 1 trial) .However, no significant difference was found on all cause death (RR=0.97,95% CI 0.06 to 15.36, p=0.9823, 1 trial) .

19.3 comparison versus CABG - summary of results

Paclitaxel eluting stent was inferior to CABG in terms of MACE (RR=1.47, 95% CI 1.17to 1.84, p=0.0000, 1 trial) and target lesion revascularisation (RR=2.32, 95% CI 1.71 to 3.16,p=0.0000, 1 trial) . No significant difference was found on all cause death (RR=1.25, 95% CI0.79 to 1.98, p=0.3448, 1 trial) and MI (fatal and non fatal) (RR=1.47, 95% CI 0.93 to 2.34,p=0.1003, 1 trial) .


No significant difference was found between Genous stent and paclitaxel eluting stent interms of MI (fatal and non fatal) (RR=0.19, 95% CI 0.02 to 1.63, p=0.1309, 1 trial) and targetlesion revascularisation (RR=1.33, 95% CI 0.56 to 3.17, p=0.5154, 1 trial) .

Sirolimus eluting stent was superior to paclitaxel eluting stent in terms of target-vesselrevascularization (RR=0.42, 95% CI 0.19 to 0.94, p=0.0357, 1 trial) , target lesion revascularisa-tion (RR=0.62, 95% CI 0.42 to 0.93, p=0.0213, 4 trials) and angiographic restenosis (RR=0.25,95% CI 0.10 to 0.60, p=0.0020, 1 trial) .However, no significant difference was found on all causedeath (RR=0.83, 95% CI 0.47 to 1.47, p=0.5323, 4 trials) , cardiac death (RR=2.00, 95% CI0.07 to 59.35, p=0.6886, 1 trial) and MI (fatal and non fatal) (RR=0.80, 95% CI 0.54 to 1.20,p=0.2848, 4 trials) .





continued...




MACE RR=0.71 0.58;0.88 0.0016 0.8622 (0.00) 2 1602




RR=0.75 0.23;2.45 0.6369 0.4273 (0.00) 2 1602


RR=3.01 0.31;29.04 0.3407 1.0000 (0.00) 1 1156


RR=0.34 0.04;3.04 0.3347 1.0000 (0.00) 1 1156




MACE RR=0.10 0.04;0.25 0.0000 1.0000 (0.00) 1 322



RR=0.20 0.02;1.65 0.1337 1.0000 (0.00) 1 322


Table 19.5: Summary of all results for comparison versus CABG


Paclitaxel eluting stent versus CABG



MACE RR=1.47 1.17;1.84 0.0000 1.0000 (0.00) 1 1800




Genous stent versus paclitaxel eluting stent





cardiac death RR=2.00 0.07;59.35 0.6886 1.0000 (0.00) 1 500





RR=0.83 0.24;2.85 0.7641 0.7074 (0.00) 4 1322








0.79 [0.30;2.07] .63 2 1602 .46 0.00


0.97 [0.06;15.36] .98 1 319 1.00 0.00

comparison versus CABG

Paclitaxel eluting stent versus CABG 1.25 [0.79;1.98] .34 1 1800 1.00 1.00



0.83 [0.47;1.47] .53 4 1322 .71 0.00












2.00 [0.07;59.35] .69 1 500 1.00 0.00











1.16 [0.71;1.88] .56 2 1602 .89 0.00




Genous stent versus paclitaxel elutingstent

0.19 [0.02;1.63] .13 1 193 1.00 0.00


0.80 [0.54;1.20] .28 4 1322 1.00 0.00










0.71 [0.58;0.88] .00 2 1602 .86 0.00


0.10 [0.04;0.25] .00 1 322 1.00 0.00














0.70 [0.53;0.93] .01 1 1156 1.00 0.00




0.42 [0.19;0.94] .04 1 500 1.00 0.00

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk









0.55 [0.39;0.77] .00 1 1156 1.00 0.00


0.08 [0.03;0.23] .00 1 319 1.00 0.00




Genous stent versus paclitaxel elutingstent

1.33 [0.56;3.17] .52 1 193 1.00 0.00


0.62 [0.42;0.93] .02 4 1322 .39 0.01











0.75 [0.23;2.45] .64 2 1602 .43 0.00


0.20 [0.02;1.65] .13 1 322 1.00 0.00




0.83 [0.24;2.85] .76 4 1322 .71 0.00












0.45 [0.14;1.40] .17 4 1322 .81 0.00











3.01 [0.31;29.04] .34 1 1156 1.00 0.00












0.34 [0.04;3.04] .33 1 1156 1.00 0.00













0.43 [0.33;0.56] .00 1 1156 1.00 1.00


0.06 [0.02;0.18] .00 1 322 1.00 1.00




0.25 [0.10;0.60] .00 1 500 1.00 0.00

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk





189


stent in long or complex lesion

20.1 Available RCTs


A total of 3 RCTs which randomized 1924 patients were identified: 2 trials compared pa-clitaxel eluting stent with bare-metal stent and 1 trial compared sirolimus eluting stent withbare-metal stent (see 20.1 page 190).


MACE data was reported in 3 trials; 3 trials reported data on angiographic restenosis ; 2trials reported data on All cause death; 1 trials reported data on target lesion revascularisation ;1 trials reported data on MI (fatal and non fatal); and 3 trials reported data on Stent thrombosis(any, end of follow up).



Table

20.1

:M

ain

study

char

act

eris

tics

-lo

ng

orco

mple

xle

sion

-co

mpar

ison

ver

sus

bare

-met

alst

ent

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Paclita

xelelu

ting

stentvers

us

bare

-meta

lst

ent

TA

XU

SV

I,2005

[1,

2]

n=

219

vs.

227

Sta

ble

or

unst

able

AP

,si

lent

isch

aem

iaw

ith

long,

com

ple

xco

ronary

art

ery

lesi

ons

TA

XU

Svs.

Expre

ss2

sten

tdouble

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:T

VR

44

centr

es,

Euro

pe

TA

XU

SV

(all

pati

ents

),2005

[3]

n=

577

vs.

579

Sta

ble

or

unst

able

AP

,si

lent

isch

aem

iaw

ith

single

coro

nary

art

ery

sten

osi

sin

cludin

gco

mple

xor

pre

vio

usl

yunst

udie

dle

sions

(req

uir

ing

2.2

5-m

m,

4.0

-mm

,and/or

mult

iple

sten

ts)

TA

XU

Svs.

bare

met

al

EX

PR

ESS-2

double

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:T

VR

66

centr

es,

Unit

edSta

tes

QC

Afo

llow

-up

dura

tion:

9m

o

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

SC

AN

DST

EN

T,

2006

[4,

5]

n=

163

vs.

159

Sta

ble

or

unst

able

AP

,re

cent

AM

I(n

on

ST

-ele

vati

on);

wit

hone

or

more

de

nov

oco

mple

xle

sions

innati

ve

coro

nary

ves

sels

(occ

luded

,bif

urc

ati

onal,

ost

ial

or

angula

ted)

Cypher

vs.

Sonic

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:M

inim

al

lum

endia

me-

ter

4ce

ntr

es,

Den

mark





All the 2 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between paclitaxeleluting stent and bare-metal stent, with a RR of 0.79 (95%CI 0.30 to 2.07, p=0.6308) in favourof paclitaxel eluting stent. In other words, all cause death was slightly lower in the paclitaxeleluting stent group , but this was not statistically significant. No heterogeneity across thesetrials was detected (p =0.4575, I2 = 0.00%).


All the 2 studies had extractable data about the number of participants with MACE. Theanalysis detected a statistically significant difference in favor of paclitaxel eluting stent in MACE,with a RR of 0.71 (95% CI 0.58 to 0.88, p=0.0016). No heterogeneity across these trials wasdetected (p =0.8622, I2 = 0.00%).

Only one of the 2 studies eligible for this comparison provided data on target-vesselrevascularization. The analysis detected a statistically significant difference in favor of pacli-taxel eluting stent in target-vessel revascularization, with a RR of 0.70 (95% CI 0.53 to 0.93,p=0.0145).

Only one of the 2 studies eligible for this comparison provided data on target lesion revas-cularisation . The analysis detected a statistically significant difference in favor of pacli-taxel eluting stent in target lesion revascularisation , with a RR of 0.55 (95% CI 0.39 to 0.77,p=0.0000).

Only one of the 2 studies eligible for this comparison provided data on angiographicrestenosis . The analysis detected a statistically significant difference in favor of paclitaxeleluting stent in angiographic restenosis , with a RR of 0.43 (95% CI 0.33 to 0.56, p=0.0000).







Table 20.2: Results details - long or complex lesion - comparison versus bare-metal stent





MACE RR=0.71 [0.58;0.88] 0.0016 0.8622 (I=0.00) 2 1602




RR=0.75 [0.23;2.45] 0.6369 0.4273 (I=0.00) 2 1602


RR=3.01 [0.31;29.04] 0.3407 1.0000 (I=0.00) 1 1156


RR=0.34 [0.04;3.04] 0.3347 1.0000 (I=0.00) 1 1156




MACE RR=0.10 [0.04;0.25] 0.0000 1.0000 (I=0.00) 1 322



RR=0.20 [0.02;1.65] 0.1337 1.0000 (I=0.00) 1 322





TAXUS VI,2005 0/219 2/227 0.26 [0.01;5.71]

TAXUS V (all patients),20 /577 /579 0.89 [0.32;2.45]

Global p ass= 0.6308 0.79 [0.30;2.07]



SCANDSTENT,2006 1/162 1/157 0.97 [0.06;15.36]

Global p ass= 0.9823 0.97 [0.06;15.36]







TAXUS VI,2005 3/219 3/227 1.04 [0.21;5.08]


Global p ass= 0.5584 1.16 [0.71;1.88]







TAXUS VI,2005 36/219 51/227 0.73 [0.50;1.07]

TAXUS V (all patients),20 84/577 120/579 0.70 [0.54;0.91]

Global p ass= 0.0016 0.71 [0.58;0.88]



SCANDSTENT,2006 5/163 48/159 0.10 [0.04;0.25]

Global p ass= 0.0000 0.10 [0.04;0.25]







Global p ass= 0.0145 0.70 [0.53;0.93]

1.00.90.80.70.60.50.50.10.20.30.40.5 0.6 0.7 0.8 0.9 1.0Relative risk







Global p ass= 0.0000 0.55 [0.39;0.77]


SCANDSTENT,2006 4/162 46/157 0.08 [0.03;0.23]

Global p ass= 0.0000 0.08 [0.03;0.23]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk





TAXUS VI,2005 1/219 3/227 0.35 [0.04;3.30]


Global p ass= 0.6369 0.75 [0.23;2.45]



SCANDSTENT,2006 1/163 5/159 0.20 [0.02;1.65]

Global p ass= 0.1337 0.20 [0.02;1.65]








Global p ass= 0.3407 3.01 [0.31;29.04]







Global p ass= 0.3347 0.34 [0.04;3.04]







Global p ass= 0.0000 0.43 [0.33;0.56]


SCANDSTENT,2006 3/163 51/159 0.06 [0.02;0.18]

Global p ass= 0.0000 0.06 [0.02;0.18]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk


196 REFERENCES

References

[1] Dawkins KD, Grube E, Guagliumi G, Banning AP, Zmudka K, Colombo A, Thuesen L, Hauptman K, MarcoJ, Wijns W, Popma JJ, Koglin J, Russell ME. Clinical efficacy of polymer-based paclitaxel-eluting stents inthe treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for theuse of drug-eluting stents in contemporary clinical practice.. Circulation 2005;112:3306-13 [PMID=16286586]

[2] Grube E, Dawkins KD, Guagliumi G, Banning AP, Zmudka K, Colombo A, Thuesen L, Hauptman K,Marco J, Wijns W, Popma JJ, Buellesfeld L, Koglin J, Russell ME. TAXUS VI 2-year follow-up: randomizedcomparison of polymer-based paclitaxel-eluting with bare metal stents for treatment of long, complex lesions..Eur Heart J 2007;28:2578-82 [PMID=17938126]

[3] Stone GW, Ellis SG, Cannon L, Mann JT, Greenberg JD, Spriggs D, O’Shaughnessy CD, DeMaio S, Hall P,Popma JJ, Koglin J, Russell ME. Comparison of a polymer-based paclitaxel-eluting stent with a bare metalstent in patients with complex coronary artery disease: a randomized controlled trial.. JAMA 2005;294:1215-23 [PMID=16160130]

[4] Kelbaek H, Thuesen L, Helqvist S, Klvgaard L, Jrgensen E, Aljabbari S, Saunamki K, Krusell LR, Jensen GV,Btker HE, Lassen JF, Andersen HR, Thayssen P, Galle A, van Weert A. The Stenting Coronary Arteries inNon-stress/benestent Disease (SCANDSTENT) trial.. J Am Coll Cardiol 2006;47:449-55 [PMID=16412876]

[5] Kelbaek H, Klvgaard L, Helqvist S, Lassen JF, Krusell LR, Engstrm T, Btker HE, Jrgensen E, SaunamkiK, Aljabbari S, Thayssen P, Galle A, Jensen GV, Thuesen L. Long-term outcome in patients treated withsirolimus-eluting stents in complex coronary artery lesions: 3-year results of the SCANDSTENT (Stent-ing Coronary Arteries in Non-Stress/Benestent Disease) trial.. J Am Coll Cardiol 2008 May 27;51:2011-6[PMID=18498953]

197

21 Detailed results for comparison versus CABG in

long or complex lesion

21.1 Available RCTs

This section gives details for trials evaluating drug eluting stent comparison versus CABGOnly one trial which randomized 1800 patients was identified: all compared paclitaxel eluting

stent with CABG (see 21.1 page 198).The average study size was 1800 patients per arm (range 897 to 903 per arm). The first

study was published in , and the last study was published in .All trials were open-label in design. All included studies were reported in English language.

We did not found any unpublished trial.Target lesion revascularisation data was reported in 1 trials; 1 trials reported data on MI

(fatal and non fatal); 1 trials reported data on MACE; and 1 trials reported data on All causedeath.

Following table 21.1 (page 198) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus CABG.

198 CHAPTER 21. DETAILS FOR COMPARISON VERSUS CABG

Table

21.1

:M

ain

study

char

acte

rist

ics

-lo

ng

orco

mple

xle

sion

-co

mpar

ison

vers

us

CA

BG

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Paclita

xelelu

ting

stentvers

us

CA

BG

SY

NT

AX

,0

[]n

=903

vs.

897

pati

ents

wit

hco

mple

xco

ronary

dis

ease

pacl

itaxel

(taxus

Expre

ssSR

)vs.

Coro

nary

Art

ery

Bypass

Surg

ery

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:M

AC

E,





The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between paclitaxel eluting stent andCABG, with a RR of 1.25 (95%CI 0.79 to 1.98, p=0.3448) in favour of CABG. In other words,all cause death was slightly lower in the CABG group , but this was not statistically significant.


The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of CABG in MACE, with a RR of 1.47 (95% CI 1.17to 1.84, p=0.0000).

The single study eligible for this comparison provided data on target lesion revasculari-sation . The analysis detected a statistically significant difference in favor of CABG in targetlesion revascularisation , with a RR of 2.32 (95% CI 1.71 to 3.16, p=0.0000).

Table 21.2: Results details - long or complex lesion - comparison versus CABG





MACE RR=1.47 [1.17;1.84] 0.0000 1.0000 (I=0.00) 1 1800





SYNTAX 39/903 31/897 1.25 [0.79;1.98]

Global p ass= 0.3448 1.25 [0.79;1.98]

1.00.80.5 1.0 1.5 2.0Relative risk


200 CHAPTER 21. DETAILS FOR COMPARISON VERSUS CABG




SYNTAX 43/903 29/897 1.47 [0.93;2.34]

Global p ass= 0.1003 1.47 [0.93;2.34]






SYNTAX 161/903 109/897 1.47 [1.17;1.84]

Global p ass= 0.0000 1.47 [1.17;1.84]

1.00.51.0 1.5 2.0Relative risk





SYNTAX 124/903 53/897 2.32 [1.71;3.16]

Global p ass= 0.0000 2.32 [1.71;3.16]



REFERENCES 201

References



eluting stent in long or complex lesion

22.1 Available RCTs


A total of 5 RCTs which randomized 1515 patients were identified: 1 trial compared Genousstent with paclitaxel eluting stent and 4 trials compared sirolimus eluting stent with paclitaxeleluting stent (see 22.1 page 203).



Target lesion revascularisation data was reported in 5 trials; 5 trials reported data on MI(fatal and non fatal); 4 trials reported data on All cause death; 1 trials reported data ontarget-vessel revascularization; 1 trials reported data on cardiac death; 1 trials reported data onangiographic restenosis ; 4 trials reported data on Stent thrombosis (any, end of follow up); and4 trials reported data on 4y stent thrombosis (ARC).



Table

22.1

:M

ain

study

chara

cter

isti

cs-

long

orco

mple

xle

sion

-co

mpar

ison

ver

sus

pacl

itaxel

eluti

ng

sten

t

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Genous

stentvers

us

paclita

xelelu

ting

stent

TR

IAS-H

R,

2008

[]n

=98

vs.

95

hig

h-r

isk

pati

ents

(long

lesi

ons,

small

ves

sels

,ch

ronic

tota

locc

lusi

ons,

or

any

lesi

on

ina

dia

bet

icpati

ent)

Gen

ous

sten

t(a

nti

body-c

oate

dbare

-met

al

sten

t)fo

llow

edby

one

month

of

dual

anti

pla

tele

tth

erapy

vs.

Taxus

or

Cypher

follow

edby

at

least

six

month

sof

dual

anti

pla

tele

tth

erapy

single

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:ta

rget

lesi

on

failure

single

cente

r,

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

Pet

ronio

etal,

2007

[1]

n=

50

vs.

50

Com

ple

xle

sions.

Sta

ble

AP

or

docu

men

ted

isch

aem

ia,

no

AM

IC

ypher

vs.

Taxus

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:N

eoin

tim

al

hyp

erpla

sia

single

cente

r,It

aly

Cer

vin

ka,

2006

[2]

n=

37

vs.

33

Com

ple

xle

sionsa

nd

pati

ents

.Sig

ns

and/or

sym

pto

ms

myoca

rdia

lis

chaem

ia,

incl

udin

gA

MI

siro

lim

us-

eluti

ng

sten

tvs.

pacl

itaxel

-elu

ting

sten

top

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:N

eoin

tim

al

hyp

erpla

sia

1ce

ntr

es,

LO

NG

DE

SII

,2006

[3]

n=

250

vs.

250

Long

lesi

ons.

AP

or

posi

tive

stre

ss,

no

AM

ISE

Svs.

PE

Ssi

ngle

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:B

inary

rest

enosi

s5

centr

es,

Kore

a

CO

RP

AL

,2005

[4]

n=

331

vs.

321

Docu

men

ted

myoca

rdia

lis

chaem

ia,

no

AM

Isi

rolim

us

vs.

pacl

itaxel

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:B

inary

rest

enosi

s2

centr

es,

Spain












All the 4 studies had extractable data about the number of participants with target le-sion revascularisation . The analysis detected a statistically significant difference in favor ofsirolimus eluting stent in target lesion revascularisation , with a RR of 0.62 (95% CI 0.42 to0.93, p=0.0213). No heterogeneity across these trials was detected (p =0.3870, I2 = 0.01%).

Only one of the 4 studies eligible for this comparison provided data on angiographicrestenosis . The analysis detected a statistically significant difference in favor of sirolimuseluting stent in angiographic restenosis , with a RR of 0.25 (95% CI 0.10 to 0.60, p=0.0020).

Table 22.2: Results details - long or complex lesion - comparison versus paclitaxel eluting stent









continued...






RR=0.83 [0.24;2.85] 0.7641 0.7074 (I=0.00) 4 1322






Petronio et al,2007 1/50 2/50 0.50 [0.05;5.34]

Cervinka,2006 1/37 0/33 1.78 [0.06;51.47]

LONG DES II,2006 2/250 0/250 4.00 [0.18;88.27]

CORPAL,2005 18/331 22/321 0.79 [0.43;1.45]

Global p ass= 0.5323 0.83 [0.47;1.47]







LONG DES II,2006 1/250 0/250 2.00 [0.07;59.35]

Global p ass= 0.6886 2.00 [0.07;59.35]







TRIAS-HR,2008 1/98 5/95 0.19 [0.02;1.63]

Global p ass= 0.1309 0.19 [0.02;1.63]


Petronio et al,2007 1/50 1/50 1.00 [0.06;15.55]

Cervinka,2006 1/37 1/33 0.89 [0.06;13.70]

LONG DES II,2006 21/250 27/250 0.78 [0.45;1.34]

CORPAL,2005 17/331 20/321 0.82 [0.44;1.54]

Global p ass= 0.2848 0.80 [0.54;1.20]







LONG DES II,2006 8/250 19/250 0.42 [0.19;0.94]

Global p ass= 0.0357 0.42 [0.19;0.94]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk






TRIAS-HR,2008 11/98 8/95 1.33 [0.56;3.17]

Global p ass= 0.5154 1.33 [0.56;3.17]


Petronio et al,2007 2/50 2/50 1.00 [0.15;6.82]

Cervinka,2006 1/37 3/33 0.30 [0.03;2.72]

LONG DES II,2006 6/250 18/250 0.33 [0.13;0.83]

CORPAL,2005 29/331 38/321 0.74 [0.47;1.17]

Global p ass= 0.0213 0.62 [0.42;0.93]







Petronio et al,2007 0/50 0/50 1.00 [0.02;49.42]

Cervinka,2006 1/37 1/33 0.89 [0.06;13.70]

LONG DES II,2006 2/250 0/250 4.00 [0.18;88.27]

CORPAL,2005 2/331 4/321 0.48 [0.09;2.63]

Global p ass= 0.7641 0.83 [0.24;2.85]




208 REFERENCES




Petronio et al,2007 0/50 0/50 1.00 [0.02;49.42]

Cervinka,2006 1/37 1/33 0.89 [0.06;13.70]

LONG DES II,2006 1/250 5/250 0.20 [0.02;1.70]

CORPAL,2005 2/331 4/321 0.48 [0.09;2.63]

Global p ass= 0.1655 0.45 [0.14;1.40]







LONG DES II,2006 6/250 24/250 0.25 [0.10;0.60]

Global p ass= 0.0020 0.25 [0.10;0.60]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk


References

[1] Petronio AS, De Carlo M, Branchitta G, Papini B, Ciabatti N, Gistri R, Cortese B, Gherarducci G, BarsottiA. Randomized comparison of sirolimus and paclitaxel drug-eluting stents for long lesions in the left anteriordescending artery: an intravascular ultrasound study.. J Am Coll Cardiol 2007;49:539-46 [PMID=17276176]

[2] Cervinka P, Costa MA, Angiolillo DJ, Spacek R, Bystron M, Kvasnk M, Veselka J, Nanda H, Futamatsu H,Futamatsu K. ”Head-to-head comparison between sirolimus-eluting and paclitaxel-eluting stents in patientswith complex coronary artery disease: an intravascular ultrasound study”.. Catheter Cardiovasc Interv2006;67:846-51 [PMID=16683273]

[3] Kim YH, Park SW, Lee SW, Park DW, Yun SC, Lee CW, Hong MK, Kim HS, Ko JK, Park JH, Lee JH,Choi SW, Seong IW, Cho YH, Lee NH, Kim JH, Chun KJ, Park SJ. Sirolimus-eluting stent versus paclitaxel-eluting stent for patients with long coronary artery disease.. Circulation 2006;114:2148-53 [PMID=17060388]

REFERENCES 209

[4] de Lezo J, Medina A, Pan M, et al.. de Lezo J, Medina A, Pan M, et al. Drug-eluting stent for complexlesions:latest angiographic data from randomized rapamycinversus paclitaxel CORPAL study. J Am Coll Cardiol2005; 45: 75A.

210 REFERENCES

REFERENCES 211

23 Ongoing studies of long or complex lesion



Table 23.1: Ongoing studies for long or complex lesion

Study Description

References

212 REFERENCES

Part VI

In-stent restenosis

213

215

24 Overview of available evidence for in-stent

restenosis

A total of 5 RCTs which randomized 1380 patients were identified. (see tables 24.1 to 24.3 )In all, 2 reports concerned comparison versus ballon angioplasty , 2 the comparison versus

brachytherapy and 1 the comparison versus paclitaxel eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 25 (page

225) for comparison versus ballon angioplasty, in section 26 (page 230 ) for comparison versusbrachytherapy and in section 27 (page 236 ) for comparison versus paclitaxel eluting stent.



216CHAPTER 24. OVERVIEW OF AVAILABLE EVIDENCE FOR IN-STENT RESTENOSIS

Table

24.1

:M

ain

study

chara

cter

isti

cs-

in-s

tent

rest

enos

is-

com

par

ison

vers

us

ballon

angio

pla

sty

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

ballon

angio

pla

sty

Paclita

xelelu

ting

stentvers

us

ballon

angio

pla

sty

ISA

R-D

ESIR

E(P

ES

vs

PT

CA

),2005

[1]

TA

XU

Svs.

ballon

angio

pla

sty

100

vs.

100

op

enP

ara

llel

gro

ups

Bin

ary

rest

enosi

sger

many

Sirolim

us

elu

ting

stentvers

us

ballon

angio

pla

sty

ISA

R-D

ESIR

E(S

ES

vs

PT

CA

),2005

[2]

Cypher

vs.

ballon

angio

pla

sty

100

vs.

100

op

enP

ara

llel

gro

ups

Bin

ary

rest

enosi

sger

many

217

Table

24.2

:M

ain

study

char

acte

rist

ics

-in

-ste

nt

rest

enos

is-

com

pari

son

vers

us

bra

chyth

erapy

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

bra

chyth

era

py

Paclita

xelelu

ting

balloon

vers

us

bra

chyth

era

py

TA

XU

SV

ISR

,2006

[1]

TA

XU

SE

xpre

ss2

vs.

angio

pla

sty

follow

edby

vasc

ula

rbra

chyth

erapy

wit

ha

bet

aso

urc

e

195

vs.

201

op

enP

ara

llel

gro

ups

Isch

emia

-dri

ven

TV

Rat

9m

onth

sN

ort

hA

mer

ica

Sirolim

us

elu

ting

stentvers

us

bra

chyth

era

py

SIS

R,

2007

[2,

3]

Sir

olim

us-

eluti

ng

sten

tsvs.

bra

chyth

erapy

259

vs.

125

op

enP

ara

llel

gro

ups

targ

etves

sel

failure

US

and

Cana-

dia

n


Table

24.3

:M

ain

study

chara

cter

isti

cs-

in-s

tent

rest

enos

is-

com

par

ison

vers

us

pacl

itaxel

eluti

ng

sten

t

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

paclita

xel

elu

ting

stent

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

ISA

R-D

ESIR

E(S

ES

vs

PE

S),

2005

[1]

Cypher

vs.

Taxus

100

vs.

100

op

enP

ara

llel

gro

ups

Bin

ary

rest

enosi

sger

many


24.1 Main results for in-stent restenosis


24.2 comparison versus ballon angioplasty - summary of results

Paclitaxel eluting stent was superior to ballon angioplasty in terms of target-vessel revas-cularization (RR=0.58, 95% CI 0.35 to 0.94, p=0.0278, 1 trial) .However, no significant differencewas found on all cause death (RR=0.33, 95% CI 0.04 to 3.15, p=0.3377, 1 trial) and MI (fataland non fatal) (RR=4.00, 95% CI 0.18 to 87.61, p=0.3787, 1 trial) .

Sirolimus eluting stent was superior to ballon angioplasty in terms of target-vesselrevascularization (RR=0.24, 95% CI 0.12 to 0.50, p=0.0000, 1 trial) .However, no significantdifference was found on all cause death (RR=0.67, 95% CI 0.11 to 3.90, p=0.6530, 1 trial) andMI (fatal and non fatal) (RR=2.00, 95% CI 0.07 to 58.95, p=0.6880, 1 trial) .

24.3 comparison versus brachytherapy - summary of results

Data were insufficient to compare Paclitaxel eluting balloon to brachytherapy. There wasan eligible trial but it did not provided sufficient information about the endpoints considered bythis meta-analysis.

Sirolimus eluting stent was superior to brachytherapy in terms of MACE (RR=0.52,95% CI 0.31 to 0.87, p=0.0131, 1 trial) , target-vessel revascularization (RR=0.50, 95% CI 0.31to 0.81, p=0.0050, 1 trial) , target lesion revascularisation (RR=0.44, 95% CI 0.26 to 0.76,p=0.0030, 1 trial) and CABG (RR=0.08, 95% CI 0.01 to 0.66, p=0.0190, 1 trial) .However, nosignificant difference was found on all cause death (RR=0.48, 95% CI 0.01 to 24.18, p=0.7153,1 trial) and MI (fatal and non fatal) (RR=6.76, 95% CI 0.39 to 118.12, p=0.1906, 1 trial) .


Sirolimus eluting stent was superior to paclitaxel eluting stent in terms of target-vesselrevascularization (RR=0.42, 95% CI 0.19 to 0.92, p=0.0294, 1 trial) .However, no significantdifference was found on all cause death (RR=2.00, 95% CI 0.18 to 21.71, p=0.5688, 1 trial) andMI (fatal and non fatal) (RR=0.50, 95% CI 0.05 to 5.43, p=0.5688, 1 trial) .

Table 24.4: Summary of all results for comparison versus ballon angioplasty


Paclitaxel eluting stent versus ballon angioplasty




Sirolimus eluting stent versus ballon angioplasty





Table 24.5: Summary of all results for comparison versus brachytherapy


Paclitaxel eluting balloon versus brachytherapy


Sirolimus eluting stent versus brachytherapy



MACE RR=0.52 0.31;0.87 0.0131 1.0000 (0.00) 1 384



CABG RR=0.08 0.01;0.66 0.0190 1.0000 (0.00) 1 384


RR=1.93 0.09;42.50 0.6767 1.0000 (0.00) 1 384








RR=0.25 0.01;5.48 0.3787 1.0000 (0.00) 1 200




comparison versus ballon angioplasty

Paclitaxel eluting stent versus ballon an-gioplasty

0.33 [0.04;3.15] .34 1 200 1.00 0.00

Sirolimus eluting stent versus ballon an-gioplasty

0.67 [0.11;3.90] .65 1 200 1.00 0.00

comparison versus brachytherapy

Sirolimus eluting stent versusbrachytherapy

0.48 [0.01;24.18] .72 1 384 1.00 0.00



2.00 [0.18;21.71] .57 1 200 1.00 0.00











4.00 [0.18;87.61] .38 1 200 1.00 0.00


2.00 [0.07;58.95] .69 1 200 1.00 0.00



6.76 [0.39;118.12] .19 1 384 1.00 0.00



0.50 [0.05;5.43] .57 1 200 1.00 0.00











0.52 [0.31;0.87] .01 1 384 1.00 0.00


1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.7 0.80.91.0Relative risk










0.58 [0.35;0.94] .03 1 200 1.00 0.00


0.24 [0.12;0.50] .00 1 200 1.00 0.00



0.50 [0.31;0.81] .01 1 384 1.00 0.00



0.42 [0.19;0.92] .03 1 200 1.00 0.00

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk










0.44 [0.26;0.76] .00 1 384 1.00 1.00


1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.7 0.80.91.0Relative risk











0.08 [0.01;0.66] .02 1 384 1.00 0.00


1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk










1.93 [0.09;42.50] .68 1 384 1.00 0.00



0.25 [0.01;5.48] .38 1 200 1.00 0.00













0.25 [0.01;5.48] .38 1 200 1.00 0.00






225

25 Detailed results for comparison versus ballon

angioplasty in in-stent restenosis

25.1 Available RCTs

This section gives details for trials evaluating drug eluting stent comparison versus ballon an-gioplasty

A total of 2 RCTs which randomized 400 patients were identified: 1 trial compared paclitaxeleluting stent with ballon angioplasty and 1 trial compared sirolimus eluting stent with ballonangioplasty (see 25.1 page 226).



Target-vessel revascularization data was reported in 2 trials; 2 trials reported data on MI(fatal and non fatal); and 2 trials reported data on All cause death.

Following table 25.1 (page 226) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus ballon angioplasty.

226 CHAPTER 25. DETAILS FOR COMPARISON VERSUS BALLON ANGIOPLASTY

Table

25.1

:M

ain

study

chara

cter

isti

cs-

in-s

tent

rest

enos

is-

com

par

ison

vers

us

ballon

angio

pla

sty

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Paclita

xelelu

ting

stentvers

us

ballon

angio

pla

sty

ISA

R-D

ESIR

E(P

ES

vs

PT

CA

),2005

[1]

n=

100

vs.

100

In-s

tent

rest

enosi

s.A

Pand/or

posi

tive

test

,pre

vio

usl

yst

ente

d,

no

AM

IT

AX

US

vs.

ballon

angio

pla

sty

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:B

inary

rest

enosi

s2

centr

es,

ger

many

Sirolim

us

elu

ting

stentvers

us

ballon

angio

pla

sty

ISA

R-D

ESIR

E(S

ES

vs

PT

CA

),2005

[2]

n=

100

vs.

100

In-s

tent

rest

enosi

s.A

Pand/or

posi

tive

test

,pre

vio

usl

yst

ente

d,

no

AM

IC

ypher

vs.

ballon

angio

pla

sty

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:B

inary

rest

enosi

s2

centr

es,

ger

many





The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between paclitaxel eluting stent andballon angioplasty, with a RR of 0.33 (95%CI 0.04 to 3.15, p=0.3377) in favour of paclitaxeleluting stent. In other words, all cause death was slightly lower in the paclitaxel eluting stentgroup , but this was not statistically significant.


The single study eligible for this comparison provided data on target-vessel revascular-ization. The analysis detected a statistically significant difference in favor of paclitaxel elutingstent in target-vessel revascularization, with a RR of 0.58 (95% CI 0.35 to 0.94, p=0.0278).


The single study eligible for this comparison provided data on all cause death. There wasno statistically significant difference in all cause death between sirolimus eluting stent and ballonangioplasty, with a RR of 0.67 (95%CI 0.11 to 3.90, p=0.6530) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant.


The single study eligible for this comparison provided data on target-vessel revascular-ization. The analysis detected a statistically significant difference in favor of sirolimus elutingstent in target-vessel revascularization, with a RR of 0.24 (95% CI 0.12 to 0.50, p=0.0000).

Table 25.2: Results details - in-stent restenosis - comparison versus ballon angioplasty










228 CHAPTER 25. DETAILS FOR COMPARISON VERSUS BALLON ANGIOPLASTY




ISAR-DESIRE (PES vs PTCA)1/100 3/100 0.33 [0.04;3.15]

Global p ass= 0.3377 0.33 [0.04;3.15]


ISAR-DESIRE (SES vs PTCA)2/100 3/100 0.67 [0.11;3.90]

Global p ass= 0.6530 0.67 [0.11;3.90]







Global p ass= 0.3787 4.00 [0.18;87.61]



Global p ass= 0.6880 2.00 [0.07;58.95]



REFERENCES 229





Global p ass= 0.0278 0.58 [0.35;0.94]



Global p ass= 0.0000 0.24 [0.12;0.50]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk


References

[1] Kastrati A, Mehilli J, von Beckerath N, Dibra A, Hausleiter J, Pache J, Schhlen H, Schmitt C, DirschingerJ, Schmig A. Sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention ofrecurrences in patients with coronary in-stent restenosis: a randomized controlled trial.. JAMA 2005;293:165-71 [PMID=15644543]


230 CHAPTER 26. DETAILS FOR COMPARISON VERSUS BRACHYTHERAPY

26 Detailed results for comparison versus

brachytherapy in in-stent restenosis

26.1 Available RCTs

This section gives details for trials evaluating drug eluting stent comparison versus brachytherapyA total of 2 RCTs which randomized 780 patients were identified: 1 trial compared pa-

clitaxel eluting balloon with brachytherapy and 1 trial compared sirolimus eluting stent withbrachytherapy (see 26.1 page 231).



Target-vessel revascularization data was reported in 1 trials; 1 trials reported data on targetlesion revascularisation ; 1 trials reported data on MI (fatal and non fatal); 1 trials reporteddata on MACE; 1 trials reported data on CABG; 1 trials reported data on All cause death; and1 trials reported data on Stent thrombosis (any, end of follow up).

Following table 26.1 (page 231) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus brachytherapy.


Table

26.1

:M

ain

study

char

acte

rist

ics

-in

-ste

nt

rest

enos

is-

com

par

ison

vers

us

bra

chyth

erapy

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Paclita

xelelu

ting

balloon

vers

us

bra

chyth

era

py

TA

XU

SV

ISR

,2006

[1]

n=

195

vs.

201

pati

ents

wit

hre

sten

oti

cle

sions

aft

erpri

or

sten

tim

pla

nta

tion

innati

ve

coro

nary

art

erie

s

TA

XU

SE

xpre

ss2

vs.

angio

pla

sty

follow

edby

vasc

ula

rbra

chyth

erapy

wit

ha

bet

aso

urc

e

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:Is

chem

ia-d

riven

TV

Rat

9m

onth

s37

centr

es,

Nort

hA

mer

ica

Sirolim

us

elu

ting

stentvers

us

bra

chyth

era

py

SIS

R,

2007

[2,

3]

n=

259

vs.

125

rest

enosi

sw

ithin

abare

met

al

sten

tSir

olim

us-

eluti

ng

sten

tsvs.

bra

chyth

erapy

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:ta

rget

ves

sel

failure

26

centr

es,

US

and

Canadia

n





No data were presented in the 1 trial identified


The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between sirolimus eluting stent andbrachytherapy, with a RR of 0.48 (95%CI 0.01 to 24.18, p=0.7153) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant.





The single study eligible for this comparison provided data on CABG. The analysis detecteda statistically significant difference in favor of sirolimus eluting stent in CABG, with a RR of0.08 (95% CI 0.01 to 0.66, p=0.0190).

Table 26.2: Results details - in-stent restenosis - comparison versus brachytherapy







MACE RR=0.52 [0.31;0.87] 0.0131 1.0000 (I=0.00) 1 384



CABG RR=0.08 [0.01;0.66] 0.0190 1.0000 (I=0.00) 1 384


RR=1.93 [0.09;42.50] 0.6767 1.0000 (I=0.00) 1 384





SISR,2007 0/259 0/125 0.48 [0.01;24.18]

Global p ass= 0.7153 0.48 [0.01;24.18]






SISR,2007 7/259 0/125 6.76 [0.39;118.12]

Global p ass= 0.1906 6.76 [0.39;118.12]






SISR,2007 26/259 24/125 0.52 [0.31;0.87]

Global p ass= 0.0131 0.52 [0.31;0.87]

1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk






SISR,2007 28/259 27/125 0.50 [0.31;0.81]

Global p ass= 0.0050 0.50 [0.31;0.81]

1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk





SISR,2007 22/259 24/125 0.44 [0.26;0.76]

Global p ass= 0.0030 0.44 [0.26;0.76]

1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk





SISR,2007 1/259 6/125 0.08 [0.01;0.66]

Global p ass= 0.0190 0.08 [0.01;0.66]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk


REFERENCES 235




SISR,2007 2/259 0/125 1.93 [0.09;42.50]

Global p ass= 0.6767 1.93 [0.09;42.50]



References

[1] Stone GW, Ellis SG, O’Shaughnessy CD, Martin SL, Satler L, McGarry T, Turco MA, Kereiakes DJ, KelleyL, Popma JJ, Russell ME. Paclitaxel-eluting stents vs vascular brachytherapy for in-stent restenosis withinbare-metal stents: the TAXUS V ISR randomized trial.. JAMA 2006 Mar 15;295:1253-63 [PMID=16531618]

[2] Reynolds MR, Pinto DS, Shi C, Walczak J, Berezin R, Holmes DR, Cohen DJ, . Cost-effectiveness ofsirolimus-eluting stents compared with vascular brachytherapy for the treatment of in-stent restenosis.. AmHeart J 2007;154:1221-7. [PMID=18035097]

[3] Holmes DR Jr, Teirstein P, Satler L, Sketch M, O’Malley J, Popma JJ, Kuntz RE, Fitzgerald PJ, Wang H,Caramanica E, Cohen SA. Sirolimus-eluting stents vs vascular brachytherapy for in-stent restenosis withinbare-metal stents: the SISR randomized trial.. JAMA 2006;295:1264-73 [PMID=16531619]



eluting stent in in-stent restenosis

27.1 Available RCTs


Only one trial which randomized 200 patients was identified: all compared sirolimus elutingstent with paclitaxel eluting stent (see 27.1 page 237).



Target-vessel revascularization data was reported in 1 trials; 1 trials reported data on MI(fatal and non fatal); 1 trials reported data on All cause death; 1 trials reported data on Stentthrombosis (any, end of follow up); and 1 trials reported data on 4y stent thrombosis (ARC).



Table

27.1

:M

ain

study

char

act

eris

tics

-in

-ste

nt

rest

enos

is-

com

par

ison

vers

us

pacl

itaxel

eluti

ng

sten

t

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

ISA

R-D

ESIR

E(S

ES

vs

PE

S),

2005

[1]

n=

100

vs.

100

In-s

tent

rest

enosi

s.A

Pand/or

posi

tive

test

,pre

vio

usl

yst

ente

d,

no

AM

IC

ypher

vs.

Taxus

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:B

inary

rest

enosi

s2

centr

es,

ger

many





The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between sirolimus eluting stent andpaclitaxel eluting stent, with a RR of 2.00 (95%CI 0.18 to 21.71, p=0.5688) in favour of paclitaxeleluting stent. In other words, all cause death was slightly lower in the paclitaxel eluting stentgroup , but this was not statistically significant.



Table 27.2: Results details - in-stent restenosis - comparison versus paclitaxel eluting stent







RR=0.25 [0.01;5.48] 0.3787 1.0000 (I=0.00) 1 200





ISAR-DESIRE (SES vs PES),2/100 1/100 2.00 [0.18;21.71]

Global p ass= 0.5688 2.00 [0.18;21.71]








Global p ass= 0.5688 0.50 [0.05;5.43]







Global p ass= 0.0294 0.42 [0.19;0.92]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk






Global p ass= 0.3787 0.25 [0.01;5.48]



240 REFERENCES





Global p ass= 0.3787 0.25 [0.01;5.48]



References


REFERENCES 241

28 Ongoing studies of in-stent restenosis



Table 28.1: Ongoing studies for in-stent restenosis

Study Description

References

242 REFERENCES

Part VII

Bypass graft lesions

243

245

29 Overview of available evidence for bypass graft

lesions

Only one trial which randomized 75 patients was identified. (see tables 29.1 to 29.1 )In all, 1 report concerned comparison versus bare-metal stent.The detailed descriptions of trials and meta-analysis results is given in section 30 (page 251)

for comparison versus bare-metal stent.The average study size was 75 patients per arm (range 37 to 38 per arm). The first study

was published in 2006, and the last study was published in 2006.All trials were open-label in design. All included studies were reported in English language.

We did not found any unpublished trial.

246CHAPTER 29. OVERVIEW OF AVAILABLE EVIDENCE FOR BYPASS GRAFT LESIONS

Table

29.1

:M

ain

study

char

acte

rist

ics

-bypas

sgr

aft

lesi

ons

-co

mpar

ison

ver

sus

bare

-met

alst

ent

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

bare

-meta

lst

ent

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

RR

ISC

,2006

[1,

2]

Cypher

vs.

BX

-Vel

oci

ty38

vs.

37

op

enP

ara

llel

gro

ups

Late

lum

enlo

ssB

elgiu

m,

The

net

her

lands

29.2. COMPARISON VERSUS BARE-METAL STENT - SUMMARY OF RESULTS 247

29.1 Main results for bypass graft lesions



Sirolimus eluting stent was superior to bare-metal stent in terms of target-vessel revas-cularization (RR=0.19, 95% CI 0.05 to 0.83, p=0.0269, 1 trial) .But sirolimus eluting stentincreased the risk of 2 yr Death (all cause) (RR=21.42, 95% CI 1.31 to 351.48, p=0.0318, 1trial) .However, no significant difference was found on all cause death (RR=1.95, 95% CI 0.07 to56.32, p=0.6978, 1 trial) , MI (fatal and non fatal) (RR=2.92, 95% CI 0.32 to 26.83, p=0.3434,1 trial) , MACE (RR=0.53, 95% CI 0.22 to 1.29, p=0.1614, 1 trial) , 2 yr MACE (RR=1.43,95% CI 0.89 to 2.30, p=0.1416, 1 trial) , 2 yr TLR (RR=2.27, 95% CI 0.64 to 8.13, p=0.2070,1 trial) and target lesion revascularisation (RR=0.24, 95% CI 0.06 to 1.07, p=0.0617, 1 trial) .





2 yr Death (all cause) RR=21.42 1.31;351.48 0.0318 1.0000 (0.00) 1 75


MACE RR=0.53 0.22;1.29 0.1614 1.0000 (0.00) 1 75

2 yr MACE RR=1.43 0.89;2.30 0.1416 1.0000 (0.00) 1 75


2 yr TLR RR=2.27 0.64;8.13 0.2070 1.0000 (0.00) 1 75






1.95 [0.07;56.32] .70 1 75 1.00 0.00







Figure 29.2: Forest’s plot for 2 yr Death (all cause)




21.42 [1.31;351.48] .03 1 75 1.00 0.00










2.92 [0.32;26.83] .34 1 75 1.00 0.00










0.53 [0.22;1.29] .16 1 75 1.00 0.00











1.43 [0.89;2.30] .14 1 75 1.00 0.00










0.19 [0.05;0.83] .03 1 75 1.00 1.00

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk









2.27 [0.64;8.13] .21 1 75 1.00 0.00











0.24 [0.06;1.07] .06 1 75 1.00 0.00






251


stent in bypass graft lesions

30.1 Available RCTs





Target-vessel revascularization data was reported in 1 trials; 1 trials reported data on targetlesion revascularisation ; 1 trials reported data on MI (fatal and non fatal); 1 trials reporteddata on MACE; 1 trials reported data on All cause death; 1 trials reported data on 2 yr TLR ;1 trials reported data on 2 yr MACE ; and 1 trials reported data on 2 yr Death (all cause) .



Table

30.1

:M

ain

study

chara

cter

isti

cs-

bypas

sgr

aft

lesi

ons

-co

mpari

son

ver

sus

bare

-met

alst

ent

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

RR

ISC

,2006

[1,

2]

n=

38

vs.

37

Sta

ble

or

unst

able

AP

,w

ith

pre

vio

us

coro

nary

art

ery

bypass

surg

ery

and

deg

ener

ate

dvei

ngra

fts

Cypher

vs.

BX

-Vel

oci

tyop

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:L

ate

lum

enlo

ss2

centr

es,

Bel

giu

m,

The

net

her

lands





The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between sirolimus eluting stent andbare-metal stent, with a RR of 1.95 (95%CI 0.07 to 56.32, p=0.6978) in favour of bare-metalstent. In other words, all cause death was slightly lower in the bare-metal stent group , but thiswas not statistically significant.

The single study eligible for this comparison provided data on 2 yr Death (all cause) .The analysis detected a statistically significant difference in favor of bare-metal stent in 2 yrDeath (all cause) , with a RR of 21.42 (95% CI 1.31 to 351.48, p=0.0318).



The single study eligible for this comparison provided data on 2 yr MACE . No statisticallysignificant difference between the groups was found in 2 yr MACE , with a RR of 1.43 (95% CI0.89 to 2.30, p=0.1416).


The single study eligible for this comparison provided data on 2 yr TLR . No statisticallysignificant difference between the groups was found in 2 yr TLR , with a RR of 2.27 (95% CI0.64 to 8.13, p=0.2070).


Table 30.2: Results details - bypass graft lesions - comparison versus bare-metal stent




2 yr Death (all cause) RR=21.42 [1.31;351.48] 0.0318 1.0000 (I=0.00) 1 75


MACE RR=0.53 [0.22;1.29] 0.1614 1.0000 (I=0.00) 1 75

2 yr MACE RR=1.43 [0.89;2.30] 0.1416 1.0000 (I=0.00) 1 75


2 yr TLR RR=2.27 [0.64;8.13] 0.2070 1.0000 (I=0.00) 1 75






RRISC,2006 1/38 0/37 1.95 [0.07;56.32]

Global p ass= 0.6978 1.95 [0.07;56.32]



Figure 30.2: Forest’s plot for 2 yr Death (all cause)



RRISC,2006 11/38 0/37 21.42 [1.31;351.48]

Global p ass= 0.0318 21.42 [1.31;351.48]






RRISC,2006 3/38 1/37 2.92 [0.32;26.83]

Global p ass= 0.3434 2.92 [0.32;26.83]







RRISC,2006 6/38 11/37 0.53 [0.22;1.29]

Global p ass= 0.1614 0.53 [0.22;1.29]






RRISC,2006 22/38 15/37 1.43 [0.89;2.30]

Global p ass= 0.1416 1.43 [0.89;2.30]






RRISC,2006 2/38 10/37 0.19 [0.05;0.83]

Global p ass= 0.0269 0.19 [0.05;0.83]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk


256 REFERENCES




RRISC,2006 7/38 3/37 2.27 [0.64;8.13]

Global p ass= 0.2070 2.27 [0.64;8.13]






RRISC,2006 2/38 8/37 0.24 [0.06;1.07]

Global p ass= 0.0617 0.24 [0.06;1.07]



References

[1] Vermeersch P, Agostoni P, Verheye S, Van den Heuvel P, Convens C, Van den Branden F, Van LangenhoveG. Increased late mortality after sirolimus-eluting stents versus bare-metal stents in diseased saphenousvein grafts: results from the randomized DELAYED RRISC Trial.. J Am Coll Cardiol 2007 Jul 17;50:261-7[PMID=17631219]

[2] Vermeersch P, Agostoni P, Verheye S, Van den Heuvel P, Convens C, Bruining N, Van den Branden F, VanLangenhove G. Randomized double-blind comparison of sirolimus-eluting stent versus bare-metal stent im-plantation in diseased saphenous vein grafts: six-month angiographic, intravascular ultrasound, and clinicalfollow-up of the RRISC Trial.. J Am Coll Cardiol 2006 Dec 19;48:2423-31 [PMID=17174178]

REFERENCES 257

31 Ongoing studies of bypass graft lesions



Table 31.1: Ongoing studies for bypass graft lesions

Study Description

ISAR-CABG (0)[] NCT00611910

DES vs. BMS

Bypass Graft Lesions

BASKET-SAVAGE (0)[] NCT00595647

Taxus vs. Libert

percutaneous coronary interventions of saphenous vein grafts

VELETI (0)[] NCT00289835

TAXUS vs. standard medical treatment

Moderate Vein Graft Lesions

References

258 REFERENCES

Part VIII

Unprotected left main coronaryartery stenosis

259

261

32 Overview of available evidence for unprotected

left main coronary artery stenosis





262CHAPTER 32. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPROTECTED LEFT MAIN CORONARY ARTERY STENOSIS

Table

32.1

:M

ain

study

char

act

eris

tics

-unpro

tect

edle

ftm

ain

coro

nar

yar

tery

sten

osis

-co

mpari

son

vers

us

bare

-met

alst

ent

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

bare

-meta

lst

ent

Paclita

xelelu

ting

stentvers

us

bare

-meta

lst

ent

Erg

lis,

2007

[1]

IVU

S-g

uid

edpacl

itaxel

-elu

ting

sten

t(T

axus

Expre

ss)

aft

erle

sion

pre

-tre

atm

ent

wit

hcu

ttin

gballoon

vs.

IVU

S-g

uid

edbare

-met

al

(Expre

ssor

Lib

erte

)aft

erle

sion

pre

-tre

atm

ent

wit

hcu

ttin

gballoon

53

vs.

50

op

enP

ara

llel

gro

ups

NA

NA


32.1 Main results for unprotected left main coronary arterystenosis



Paclitaxel eluting stent was superior to bare-metal stent in terms of MACE (RR=0.44,95% CI 0.20 to 0.99, p=0.0470, 1 trial) and target lesion revascularisation (RR=0.12, 95% CI0.02 to 0.91, p=0.0402, 1 trial) .However, no significant difference was found on all cause death(RR=0.94, 95% CI 0.06 to 14.68, p=0.9668, 1 trial) , cardiac death (RR=1.89, 95% CI 0.06 to55.02, p=0.7122, 1 trial) and MI (fatal and non fatal) (RR=0.67, 95% CI 0.23 to 1.99, p=0.4740,1 trial) .





cardiac death RR=1.89 0.06;55.02 0.7122 1.0000 (0.00) 1 103


MACE RR=0.44 0.20;0.99 0.0470 1.0000 (0.00) 1 103






0.94 [0.06;14.68] .97 1 103 1.00 0.00






264CHAPTER 32. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPROTECTED LEFT MAIN CORONARY ARTERY STENOSIS





1.89 [0.06;55.02] .71 1 103 1.00 0.00










0.67 [0.23;1.99] .47 1 103 1.00 0.00










0.44 [0.20;0.99] .05 1 103 1.00 0.00

1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.7 0.80.91.0Relative risk










0.12 [0.02;0.91] .04 1 103 1.00 0.00

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk







stent in unprotected left main coronary artery

stenosis

33.1 Available RCTs


Only one trial which randomized 103 patients was identified: all compared paclitaxel elutingstent with bare-metal stent (see 33.1 page 267).



Target lesion revascularisation data was reported in 1 trials; 1 trials reported data on MI(fatal and non fatal); 1 trials reported data on MACE; 1 trials reported data on cardiac death;and 1 trials reported data on All cause death.



Table

33.1

:M

ain

study

chara

cter

isti

cs-

unpro

tect

edle

ftm

ain

coro

nar

yar

tery

sten

osi

s-

com

pari

son

vers

us

bare

-met

alst

ent

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Paclita

xelelu

ting

stentvers

us

bare

-meta

lst

ent

Erg

lis,

2007

[1]

n=

53

vs.

50

per

cuta

neo

us

coro

nary

inte

rven

tion

for

unpro

tect

edle

ftm

ain

art

ery

sten

osi

sIV

US-g

uid

edpacl

itaxel

-elu

ting

sten

t(T

axus

Expre

ss)

aft

erle

sion

pre

-tre

atm

ent

wit

hcu

ttin

gballoon

vs.

IVU

S-g

uid

edbare

-met

al

(Expre

ssor

Lib

erte

)aft

erle

sion

pre

-tre

atm

ent

wit

hcu

ttin

gballoon

No

of

sten

tp

erle

sions:

1.0

2

op

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:N

A,

NA





The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between paclitaxel eluting stent andbare-metal stent, with a RR of 0.94 (95%CI 0.06 to 14.68, p=0.9668) in favour of paclitaxeleluting stent. In other words, all cause death was slightly lower in the paclitaxel eluting stentgroup , but this was not statistically significant.



The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of paclitaxel eluting stent in MACE, with a RR of0.44 (95% CI 0.20 to 0.99, p=0.0470).

The single study eligible for this comparison provided data on target lesion revasculari-sation . The analysis detected a statistically significant difference in favor of paclitaxel elutingstent in target lesion revascularisation , with a RR of 0.12 (95% CI 0.02 to 0.91, p=0.0402).

Table 33.2: Results details - unprotected left main coronary artery stenosis - comparison versusbare-metal stent






MACE RR=0.44 [0.20;0.99] 0.0470 1.0000 (I=0.00) 1 103





Erglis,2007 1/53 1/50 0.94 [0.06;14.68]

Global p ass= 0.9668 0.94 [0.06;14.68]







Erglis,2007 1/53 0/50 1.89 [0.06;55.02]

Global p ass= 0.7122 1.89 [0.06;55.02]






Erglis,2007 5/53 7/50 0.67 [0.23;1.99]

Global p ass= 0.4740 0.67 [0.23;1.99]






Erglis,2007 7/53 15/50 0.44 [0.20;0.99]

Global p ass= 0.0470 0.44 [0.20;0.99]

1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk


270 REFERENCES




Erglis,2007 1/53 8/50 0.12 [0.02;0.91]

Global p ass= 0.0402 0.12 [0.02;0.91]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk


References

[1] Erglis A, Narbute I, Kumsars I, Jegere S, Mintale I, Zakke I, Strazdins U, Saltups A. A randomized com-parison of paclitaxel-eluting stents versus bare-metal stents for treatment of unprotected left main coronaryartery stenosis.. J Am Coll Cardiol 2007;50:491-7 [PMID=17678730]

REFERENCES 271

34 Ongoing studies of unprotected left main

coronary artery stenosis



Table 34.1: Ongoing studies for unprotected left main coronary artery stenosis

Study Description

ISAR-LEFT-MAIN (0)[] NCT00133237

Sirolimus-eluting stent vs. Paclitaxel-eluting stent

Unprotected Left Main Coronary Artery Disease

LEFT-MAIN-2 (0)[] NCT00598637

Xience vs. Endeavor Resolute

unprotected left main coronary artery disease

Leipzig (0)[] NCT00176397

PCI With DES vs. CABG

left main coronary stenosis

References

272 REFERENCES

Part IX

Total occlusion

273

275

35 Overview of available evidence for total occlusion



was published in 2006, and the last study was published in 2006.Erreur ??? 0 et 0.All included studies were reported in English language. We did not found any unpublished

trial.

276 CHAPTER 35. OVERVIEW OF AVAILABLE EVIDENCE FOR TOTAL OCCLUSION

Table

35.1

:M

ain

study

char

acte

rist

ics

-to

talocc

lusi

on-

com

par

ison

vers

us

bare

-met

alst

ent

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

bare

-meta

lst

ent

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

PR

ISO

NII

,2006

[1]

Cypher

vs.

BxV

eloci

ty100

vs.

100

single

-blind

Para

llel

gro

ups

Bin

ary

rest

enosi

sB

elgiu

m


35.1 Main results for total occlusion



Sirolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.20,95% CI 0.07 to 0.56, p=0.0024, 1 trial) , target-vessel revascularization (RR=0.36, 95% CI 0.17to 0.78, p=0.0091, 1 trial) , target lesion revascularisation (RR=0.21, 95% CI 0.07 to 0.60,p=0.0034, 1 trial) and angiographic restenosis (RR=0.19, 95% CI 0.09 to 0.42, p=0.0000, 1trial) .However, no significant difference was found on all cause death (RR=1.00, 95% CI 0.02 to49.91, p=1.0000, 1 trial) and MI (fatal and non fatal) (RR=0.67, 95% CI 0.11 to 3.90, p=0.6530,1 trial) .






MACE RR=0.20 0.07;0.56 0.0024 1.0000 (0.00) 1 200




RR=4.00 0.18;87.61 0.3787 1.0000 (0.00) 1 200






1.00 [0.02;49.91] 1.00 1 200 1.00 0.00






278 CHAPTER 35. OVERVIEW OF AVAILABLE EVIDENCE FOR TOTAL OCCLUSION





0.67 [0.11;3.90] .65 1 200 1.00 0.00










0.20 [0.07;0.56] .00 1 200 1.00 0.00

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk









0.36 [0.17;0.78] .01 1 200 1.00 1.00

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk










0.21 [0.07;0.60] .00 1 200 1.00 0.00

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk









4.00 [0.18;87.61] .38 1 200 1.00 0.00










0.19 [0.09;0.42] .00 1 200 1.00 1.00

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk







stent in total occlusion

36.1 Available RCTs





trial.Target-vessel revascularization data was reported in 1 trials; 1 trials reported data on target

lesion revascularisation ; 1 trials reported data on MI (fatal and non fatal); 1 trials reporteddata on MACE; 1 trials reported data on angiographic restenosis ; 1 trials reported data on Allcause death; and 1 trials reported data on Stent thrombosis (any, end of follow up).



Table

36.1

:M

ain

study

char

acte

rist

ics

-to

talocc

lusi

on-

com

par

ison

vers

us

bare

-met

alst

ent

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Sirolim

us

elu

ting

stentvers

us

bare

-meta

lst

ent

PR

ISO

NII

,2006

[1]

n=

100

vs.

100

Chro

nic

tota

locc

lusi

on,

posi

tive

exer

cise

stre

sste

stC

ypher

vs.

BxV

eloci

tysi

ngle

-blind

Para

llel

gro

ups

Pri

mary

endp

oin

t:B

inary

rest

enosi

s2

centr

es,

Bel

giu

m











Table 36.2: Results details - total occlusion - comparison versus bare-metal stent





MACE RR=0.20 [0.07;0.56] 0.0024 1.0000 (I=0.00) 1 200




RR=4.00 [0.18;87.61] 0.3787 1.0000 (I=0.00) 1 200






PRISON II,2006 0/100 0/100 1.00 [0.02;49.91]

Global p ass= 1.0000 1.00 [0.02;49.91]






PRISON II,2006 2/100 3/100 0.67 [0.11;3.90]

Global p ass= 0.6530 0.67 [0.11;3.90]






PRISON II,2006 4/100 20/100 0.20 [0.07;0.56]

Global p ass= 0.0024 0.20 [0.07;0.56]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk






PRISON II,2006 8/100 22/100 0.36 [0.17;0.78]

Global p ass= 0.0091 0.36 [0.17;0.78]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk





PRISON II,2006 4/100 19/100 0.21 [0.07;0.60]

Global p ass= 0.0034 0.21 [0.07;0.60]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk





PRISON II,2006 2/100 0/100 4.00 [0.18;87.61]

Global p ass= 0.3787 4.00 [0.18;87.61]



REFERENCES 285




PRISON II,2006 7/100 36/100 0.19 [0.09;0.42]

Global p ass= 0.0000 0.19 [0.09;0.42]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk


References

[1] Suttorp MJ, Laarman GJ, Rahel BM, Kelder JC, Bosschaert MA, Kiemeneij F, Ten Berg JM, Bal ET, Rens-ing BJ, Eefting FD, Mast EG. Primary Stenting of Totally Occluded Native Coronary Arteries II (PRISONII): a randomized comparison of bare metal stent implantation with sirolimus-eluting stent implantation forthe treatment of total coronary occlusions.. Circulation 2006;114:921-8 [PMID=16908768]

286 REFERENCES

REFERENCES 287

37 Ongoing studies of total occlusion



Table 37.1: Ongoing studies for total occlusion

Study Description

PRISON III (2007)[1] NCT00428454

Endeavor vs. Cypher

patients with total coronary occlusions for at least 2 weeks with evi-dence of ischemia related to the occluded coronary artery

GISSOC II (0)[] NCT00220558

Cypher Select-TM Sirolimus Eluting Stent vs. SONIC-TM Bare MetalStent

Chronic Total Occlusion lesions

References

[1] Suttorp MJ, Laarman GJ. A randomized comparison of sirolimus-eluting stent implantation withzotarolimus-eluting stent implantation for the treatment of total coronary occlusions: rationale and de-sign of the PRImary Stenting of Occluded Native coronary arteries III (PRISON III) study.. Am Heart J2007 Sep;154:432-5 [PMID=17719285]

288 REFERENCES

Part X

Bifurcation

289

291

38 Overview of available evidence for bifurcation

Only one trial which randomized 205 patients was identified. (see tables 38.1 to 38.1 )In all, 1 report concerned comparison versus paclitaxel eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 39 (page 295)

for comparison versus paclitaxel eluting stent.The average study size was 205 patients per arm (range 102 to 103 per arm). The first study



292 CHAPTER 38. OVERVIEW OF AVAILABLE EVIDENCE FOR BIFURCATION

Table

38.1

:M

ain

study

char

acte

rist

ics

-bifurc

atio

n-

com

par

ison

ver

sus

pacl

itaxel

eluti

ng

sten

t

Tri

al

Com

pari

son

Eff

ecti

ves

Blindin

gD

esi

gn

Pri

mary

endp

oin

tL

ocalisa

tion

com

pari

son

vers

us

paclita

xel

elu

ting

stent

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

Pan,

2007

[1]

SE

Svs.

PE

S103

vs.

102

op

enP

ara

llel

gro

ups

none

Spain


38.1 Main results for bifurcation



Sirolimus eluting stent was superior to paclitaxel eluting stent in terms of target lesionrevascularisation (RR=0.30, 95% CI 0.10 to 0.90, p=0.0321, 1 trial) .However, no significantdifference was found on all cause death (RR=0.66, 95% CI 0.11 to 3.87, p=0.6453, 1 trial) andMI (fatal and non fatal) (RR=0.99, 95% CI 0.14 to 6.90, p=0.9921, 1 trial) .











0.66 [0.11;3.87] .65 1 205 1.00 0.00






294 CHAPTER 38. OVERVIEW OF AVAILABLE EVIDENCE FOR BIFURCATION





0.99 [0.14;6.90] .99 1 205 1.00 0.00










0.30 [0.10;0.90] .03 1 205 1.00 0.00

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk





295


eluting stent in bifurcation

39.1 Available RCTs


Only one trial which randomized 205 patients was identified: all compared sirolimus elutingstent with paclitaxel eluting stent (see 39.1 page 296).



Target lesion revascularisation data was reported in 1 trials; 1 trials reported data on MI(fatal and non fatal); and 1 trials reported data on All cause death.



Table

39.1

:M

ain

study

chara

cter

isti

cs-

bifurc

atio

n-

com

par

ison

ver

sus

pac

lita

xel

eluti

ng

sten

t

Tri

al

Pati

ents

Tre

atm

ents

Desi

gn

Sirolim

us

elu

ting

stentvers

us

paclita

xelelu

ting

stent

Pan,

2007

[1]

n=

103

vs.

102

pati

ents

wit

hbif

urc

ati

on

lesi

ons

SE

Svs.

PE

Sop

enP

ara

llel

gro

ups

Pri

mary

endp

oin

t:none

2ce

ntr

es,

Spain





The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between sirolimus eluting stent andpaclitaxel eluting stent, with a RR of 0.66 (95%CI 0.11 to 3.87, p=0.6453) in favour of sirolimuseluting stent. In other words, all cause death was slightly lower in the sirolimus eluting stentgroup , but this was not statistically significant.



Table 39.2: Results details - bifurcation - comparison versus paclitaxel eluting stent









Pan,2007 2/103 3/102 0.66 [0.11;3.87]

Global p ass= 0.6453 0.66 [0.11;3.87]



298 REFERENCES




Pan,2007 2/103 2/102 0.99 [0.14;6.90]

Global p ass= 0.9921 0.99 [0.14;6.90]






Pan,2007 4/103 13/102 0.30 [0.10;0.90]

Global p ass= 0.0321 0.30 [0.10;0.90]

1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk


References

[1] Pan M, Surez de Lezo J, Medina A, Romero M, Delgado A, Segura J, Ojeda S, Mazuelos F, HernandezE, Melian F, Pavlovic D, Esteban F, Herrador J. Drug-eluting stents for the treatment of bifurcation le-sions: a randomized comparison between paclitaxel and sirolimus stents.. Am Heart J 2007 Jan;153:15.e1-7[PMID=17174630]

REFERENCES 299

40 Ongoing studies of bifurcation



Table 40.1: Ongoing studies for bifurcation

Study Description

Nordic Bifurcation StentTechnique Study (0)[] NCT00292305

crush stenting vs. culotte stenting

bifurcation lesions

Nordic Bifurcation Study(0)[] NCT00376571

Strategy of Routine Stenting Both Main Vessel and Side Branch vs.Strategy of Routine Main Vessel Stenting and Optional Treatment ofSide Branch

bifurcation lesions

References

300 REFERENCES

Index

comparison versus ballon angioplasty, 225results table, 219Trials description, 216

comparison versus bare-metal stent, 29, 92, 129,160, 189, 251, 266, 280

results table, 15, 83, 120, 154, 181, 247,263, 277

Trials description, 10, 80, 118, 152, 178,246, 262, 276

comparison versus brachytherapy, 230results table, 220Trials description, 217

comparison versus CABG, 197results table, 182Trials description, 179

comparison versus paclitaxel eluting stent, 53,103, 140, 166, 202, 236, 295

results table, 17, 84, 121, 154, 182, 220, 293Trials description, 12, 81, 119, 153, 180,

218, 292comparison versus rapamycin eluting stent, 110

results table, 84Trials description, 82

comparison versus sirolimus eluting stent, 66results table, 17Trials description, 13

ACTION, 10, 30reference, 50

Acute myocardial infarction, 115available trials, 117excluded studies, 147main results, 120

ASPECT, 11, 32reference, 51

BASKET (vs paclitaxel), 12, 55reference, 65

BASKET-PROVE, 75reference, 76

BASKET-SAVAGE, 257Bifurcation, 289bifurcation

available trials, 291

excluded studies, 299main results, 293

Bypass graft lesions, 243bypass graft lesions

available trials, 245excluded studies, 257main results, 247

C-SIRIUS, 11, 33reference, 52

Cervinka, 180, 203reference, 208

COMBAT, 75CORPAL, 180, 203

reference, 209Costar II, 12, 54

reference, 64

DECODE, 80, 94reference, 102

DEDICATION, 118, 130reference, 139

DELIVER, 11, 32reference, 51

DESSERT, 80, 93reference, 102

Di Lorenzo et al., 119, 141reference, 146

DIABEDES IV, 113DIABETES, 80, 94

reference, 102Diabetic patients, 77


Daz de la Llera, 118, 130reference, 139

E-SIRIUS, 11, 33reference, 52

ELUTES, 11, 32reference, 51

ENDEAVOR II, 11, 34reference, 52

301

302 INDEX

ENDEAVOR III, 13, 67reference, 74

ENDEAVOR IV, 76reference, 76

Erglis, 262, 267reference, 270

FEMH-93005, 75FRE-RACE, 76FREEDOM, 113FUTURE I, 10, 30

reference, 51FUTURE II, 10, 30

reference, 50

GENESIS Trial CP-01, 75GISSOC II, 287

HAAMU-STENT, 118, 130reference, 139

Han, 12, 54reference, 64

In-stent restenosis, 213in-stent restenosis


ISAR-CABG, 257ISAR-DESIRE (PES vs PTCA), 216, 226

reference, 229ISAR-DESIRE (SES vs PES), 218, 237

reference, 240ISAR-DESIRE (SES vs PTCA), 216, 226

reference, 229ISAR-DIABETES, 81, 104

reference, 109ISAR-LEFT-MAIN, 271ISAR-SMART 3, 153, 167

reference, 172ISAR-test (diabetics), 82, 111

reference, 112ISAR-TEST-1, 12, 54

reference, 64

Kim, 81, 104reference, 109

Kochiadakis, 11, 33reference, 52

Korean Randomized Study, 75

LEADERS, 13, 67reference, 74

LEFT-MAIN-2, 271Leipzig, 271Lipsia-Yukon-DM, 113LONG DES II, 180, 203

reference, 208Long or complex lesion, 175long or complex lesion


MIDCAB Versus DES in Proximal LAD Le-sions, 75

MISSION, 118, 130reference, 139

Munich Study, 75

Nordic Bifurcation Stent Technique Study, 299Nordic Bifurcation Study, 299

Ortolani et al, 11, 32reference, 51

Pache et al, 11, 33reference, 52

Pan, 292, 296reference, 298

Pasceri, 118, 131reference, 139

PASSION, 118, 130reference, 139

PATENCY, 11, 32reference, 51

PEPCAD III, 75PEPCAD IV, 113PERSEUS WH, 75Petronio et al, 180, 203

reference, 208PRISON II, 276, 281

reference, 285PRISON III, 287

reference, 287PROSIT, 119, 141

reference, 146PROTECT, 75

RAVEL, 11, 34reference, 52

Ravel (diabetics), 80, 94reference, 102

REALITY, 12, 55reference, 64

REALITY (diabetics), 81, 104

INDEX 303

reference, 109RES-ELUTION, 75REVASCULARIZE, 75RRISC, 246, 252

reference, 256

SCANDSTENT, 178, 190reference, 196

SCORE, 10, 31reference, 51

SCORPIUS, 80, 93reference, 102

SES-SMART, 152, 161reference, 165

SES-SMARt (diabetics), 80, 94reference, 102

SESAMI, 118, 131reference, 139

SIRIUS, 11, 33reference, 52

SIRIUS (diabetics), 80, 94reference, 102

SIRTAX (small vessels subgroup), 153, 167reference, 172

SIRTAX (Windecker), 12, 55reference, 64

SIRTAX diabetics, 81, 104reference, 109

SISR, 217, 231reference, 235

Small vessels, 149small vessels


SORT OUT II, 12, 54reference, 64

SORT OUT IV, 75SPIRIT I, 10, 30

reference, 51SPIRIT II, 10, 31SPIRIT III, 10, 30

reference, 50SPIRIT IV, 76SYNTAX, 179, 198

TAXi, 12, 55reference, 65

TAxi (diabetics), 81, 104TAXUS I, 10, 31

reference, 51TAXUS II, 10, 31

reference, 51TAXUS II (diabetics), 80, 93

reference, 102TAXUS IV, 10, 31

reference, 51TAXUS IV (diabetics), 80, 93

reference, 102TAXUS V (all patients), 178, 190

reference, 196TAXUS V (diabetics), 80, 93

reference, 102TAXUS V ISR, 217, 231

reference, 235TAXUS VI, 178, 190

reference, 196TAXUS VI (diabetics), 80, 93

reference, 101Tomai, 81, 104

reference, 109Total occlusion, 273total occlusion


TRIAS-HR, 180, 203TRIAS-Low-Risk , 75TYPHOON, 118, 131

reference, 139

Unparticular patients, 7available trials, 9excluded studies, 75main results, 14

Unprotected left main coronary artery stenosis,259

unprotected left main coronary artery stenosisavailable trials, 261excluded studies, 271main results, 263

VELETI, 257

Wessely, 12, 54reference, 64

ZEST, 75ZEST AMI, 147Zhang (SES vs PES), 12, 54

reference, 64ZoMaxx phase 2, 75

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