Drug -eluting stents Are they all equal? · Kandzari D.Kandzari D.et.al. “ et.al. “Comparison...

Drug-eluting stents

HCS Working Group Seminars

Macedonia Pallas Hotel, Friday 21st February 2014

Drug-eluting stents

Are they all equal?

VassilisVassilis SpanosSpanosInterventional Cardiologist, As. Director 3Interventional Cardiologist, As. Director 3rdrd Cardiology ClinicCardiology Clinic

Euroclinic Hospital, AthensEuroclinic Hospital, Athens

Drug-eluting stents

HCS Working Group Seminars

Macedonia Pallas Hotel, Friday 21st February 2014

Drug-eluting stents

How do I choose between them?

VassilisVassilis SpanosSpanosInterventional Cardiologist, As. Director 3Interventional Cardiologist, As. Director 3rdrd Cardiology ClinicCardiology Clinic

Euroclinic Hospital, AthensEuroclinic Hospital, Athens

••InIn--stent restenosis is the result of:stent restenosis is the result of:

••Inappropriate stent expansion Inappropriate stent expansion oror

Mechanisms of inMechanisms of in--stent restenosis stent restenosis

V Spanos et al. The challenge of in-stent restenosis: insights from intravascular ultrasound – review article

(Eur Heart J. 2003 Jan;24(2):138-50 )

••NeointimalNeointimal hyperplasia hyperplasia oror

••bothboth

Sirolimus-eluting stent: overcoming restenosis

Sousa JE et al. Lack of Neointimal Proliferation After Implantation of Sirolimus-Coated Stents in Human

Coronary Arteries : A Quantitative Coronary Angiography and Three-Dimensional Intravascular Ultrasound

Study ( Circulation. 2001;103:192-195 )

An unsuccessful trial - QuaDDS stent

F. Liistro, A. Colombo: Late acute thrombosis after paclitaxel eluting stent implantation

(Heart 2001;86:262-264 )

““CONCLUSIONCONCLUSION: : This single case report highlights the problem that late coronary thrombosis following paclitaxel This single case report highlights the problem that late coronary thrombosis following paclitaxel

eluting stent implantation may be an important limitation of restenosis prevention by some drug eluting stents. eluting stent implantation may be an important limitation of restenosis prevention by some drug eluting stents.

In the absence of other data, we think that combined antiplatelet treatment should be continued in the long term, In the absence of other data, we think that combined antiplatelet treatment should be continued in the long term,

unless it is contraindicatedunless it is contraindicated””

DES: a lot of different devices

EfficacyEfficacy SafetySafety


EfficacyEfficacy

•• Late Lumen Loss Late Lumen Loss

•• Intimal Hyperplasia (IVUS)Intimal Hyperplasia (IVUS)

SafetySafety

•• Complete endotthelization (OCT)Complete endotthelization (OCT)

•• Incomplete apposition (IVUS)Incomplete apposition (IVUS)•• Intimal Hyperplasia (IVUS)Intimal Hyperplasia (IVUS)

•• RestenosisRestenosis

•• Repeat RevascularizationRepeat Revascularization

•• TVF (Death, CVA, MI)TVF (Death, CVA, MI)

•• Incomplete apposition (IVUS)Incomplete apposition (IVUS)

•• Stent thrombosisStent thrombosis

•• MIMI

•• TVF (Death, CVA, TVR)TVF (Death, CVA, TVR)

Late Lumen Loss with DES

Ellis SG et al: “Relationship between angiographic late loss and target lesion revascularization after coronary stent

implantation: Analysis from the TAXUS-IV trial” J Am Coll Cardiol. 2005;45(8):1193-1200

0.09mm

0.31mm

Taxus vs. Cypher – REALITY study

MC. Morice et. al. “Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the

REALITY trial: a randomized controlled trial” JAMA 2006: 295; 895-904

Taxus vs. Cypher: SIRTAX study

CLINICAL FU onlyCLINICAL FU only

MACE at 9 months was MACE at 9 months was 6.2%6.2% in the in the

Cypher vs. Cypher vs. 10.8%10.8% in the Taxus group in the Taxus group

S. Windecker et.al. “Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization”

N Engl J Med 2005;353:653-662

Cypher vs. Cypher vs. 10.8%10.8% in the Taxus group in the Taxus group

((p=0.009p=0.009) )

Difference driven by a lower rate of Difference driven by a lower rate of

TLR (4.8% vs. 8.3%. p=0.03)TLR (4.8% vs. 8.3%. p=0.03)

RRestenosisestenosis 6.66.6% vs.% vs. 11.711.7%% ((pp=0.02)=0.02)

Taxus vs. Cypher stent: small vessels

Lesions in vessels<2.8mm received Lesions in vessels<2.8mm received

either Taxus stents (n=180) oreither Taxus stents (n=180) or

Cypher (n=180) Cypher (n=180)

Taxus stents did not reach theTaxus stents did not reach the nonnon--

J. Mehilli et.al. “Randomized trial of paclitaxel- and sirolimus-eluting stents in small coronary vessels”

Eur Heart J 2006;27:260-266

Taxus stents did not reach theTaxus stents did not reach the nonnon--

inferiorityinferiority marginmargin ofof 0.16mm0.16mm late late

lumen losslumen loss

RRestenosis estenosis rate rate waswas 19.0% 19.0% (Taxus) (Taxus)

vs.vs. 11.4% 11.4% (Cypher, p(Cypher, p=0.047)=0.047)

TTLR was LR was 14.7% 14.7% vs.vs. 6.6% 6.6%

respectivelyrespectively ((pp=0.008)=0.008)

Taxus vs. Cypher: ISAR-DIABETES250 250 ptspts with DM randomly assigned with DM randomly assigned

to receive Taxus or Cypher stentsto receive Taxus or Cypher stents

InIn--segment late luminal loss was segment late luminal loss was

0.24mm greater in the Taxus stent 0.24mm greater in the Taxus stent

group (p=0.002)group (p=0.002)

A. Dibra et.al. “Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic

patients” N Engl J Med 2005;353:663-670

group (p=0.002)group (p=0.002)

InIn--segment restenosis rate was segment restenosis rate was

16.5% for Taxus vs. 6.9% for 16.5% for Taxus vs. 6.9% for

Cypher group (p=0.03)Cypher group (p=0.03)

TLR rate was 12.0% for Taxus vs. TLR rate was 12.0% for Taxus vs.

6.4% for Cypher group (p=0.13). 6.4% for Cypher group (p=0.13).


EfficacyEfficacy



SafetySafety








•• MIMI


Offsetting impact of ST and restenosis

on the occurrence of death/MI

G. Stone et.al. “Offsetting impact of thrombosis and restenosis on the occurrence of death and

myocardial infarction after paclitaxel-eluting and bare metal stent implantation ”

Circulation 2007 Jun 5;115(22):2842-7

Late stent thrombosis

E. McFadden et al. “Late thrombosis in DES after discontinuation of antiplatelet therapy”

Lancet.2004; 364:1519-1521


EfficacyEfficacy



SafetySafety








•• MIMI


Sirolimus-eluting stent: overcoming restenosis

Sousa JE et al. Lack of Neointimal Proliferation After Implantation of Sirolimus-Coated Stents in Human

Coronary Arteries : A Quantitative Coronary Angiography and Three-Dimensional Intravascular Ultrasound

Study ( Circulation. 2001;103:192-195 )


More stent thromboses with

Taxus (13, 1.9%) than Cypher



Taxus (13, 1.9%) than Cypher

(5, 0.7%), although the

difference did not reach

statistical significance


EfficacyEfficacy



SafetySafety








•• MIMI


Incomplete strut coverage in Late STKo et al Davlouros et al Miyazaki et al Guagliumi et al Alfonso et al

n 18 DES 7 DES 6 DES 18 DES 8 BMS/ 7 DES

DES type 14 SES/ 3

PES/ 1

EES

N/A 5SES/ 1PES 6 SES/ 10 PES/

1 EES/ 1 ZES

N/A

EES

Interval

(months)

40±20 8 (3-62) 37±12 21 (6-60) 43±51

Uncovered

struts

- 32% 29% 12.3% -

Patients with

uncovered

struts

50% 100% 100% 83.3% 60%

Ko et al, Int J Cardiovasc Img 2012, Davlouros et al, Circ J 2011, Miyazaki et al, Circ J 2012, Guagliumi et al, JACC

Intv 2012, Anfonso et al, Heart 2012

DES coverage by OCT

Papayannis AC et al, CCI 2012, Gutierrez-Chico JL et al, EHJ CI 2012

DES coverage by OCT: Discrepancy between

differences in coverage and clinical outcome


EfficacyEfficacy



SafetySafety








•• MIMI



DES proven superior to BMS and DES proven superior to BMS and

used extensively in everyday practice used extensively in everyday practice

in USA & Europein USA & Europe

Cypher stentCypher stent

Taxus stentTaxus stent

DES proven superior to BMSDES proven superior to BMS

DES proven nonDES proven non--inferior to either inferior to either

Cypher or Taxus Cypher or Taxus

DES tested in clinical studies and/or DES tested in clinical studies and/or

used in everyday practice in Europeused in everyday practice in Europe

The Endeavor stent: ENDEAVOR II Study

TVFTVF at 9 months was at 9 months was

reduced from 15.1% to reduced from 15.1% to

7.9% with the Endeavor 7.9% with the Endeavor

((pp=0.0001)=0.0001)

FajadetFajadet J.J. et.al. “et.al. “Randomized, doubleRandomized, double--blind, multicenter study of the Endeavor blind, multicenter study of the Endeavor zotarolimuszotarolimus--eluting eluting

phosphorylcholinephosphorylcholine--encapsulated stent for treatment of native coronary artery lesions: clinical and encapsulated stent for treatment of native coronary artery lesions: clinical and

angiographic results of the ENDEAVOR II trial” Circulation 2006; 114angiographic results of the ENDEAVOR II trial” Circulation 2006; 114: 798: 798--806806

((pp=0.0001)=0.0001)

The rate of inThe rate of in--segment segment

restenosis was reduced from restenosis was reduced from

35.0% to 13.2% with 35.0% to 13.2% with

Endeavor (Endeavor (pp<0.0001)<0.0001)

End points Endeavor

(n=282)

Cypher

(n=94)

p

In-stent mean lumen diameter (mm) 2.08 2.52 <0.001

In-segment mean lumen diameter (mm) 1.92 2.16 <0.001

In-stent diameter stenosis (%) 24.3 11.0 <0.001

The Endeavor stent: ENDEAVOR III Study

In-stent diameter stenosis (%) 24.3 11.0 <0.001

In-segment diameter stenosis (%) 29.9 23.9 <0.001

In-stent binary restenosis (%) 9.2 2.1 0.02

In-segment binary restenosis (%) 11.7 4.3 0.04

In-stent late loss (mm) 0.60 0.15 <0.001

In-segment late loss (mm) 0.34 0.13 <0.001

Kandzari D.Kandzari D. et.al. “et.al. “Comparison of zotarolimusComparison of zotarolimus--eluting and sirolimuseluting and sirolimus--eluting stents in patients with eluting stents in patients with

native coronary artery disease: a randomized controlled trial” JACC 2006; 46native coronary artery disease: a randomized controlled trial” JACC 2006; 46: 2440: 2440--4747

Late Lumen Loss with DES

Ellis SG et al: “Relationship between angiographic late loss and target lesion revascularization after coronary stent

implantation: Analysis from the TAXUS-IV trial” J Am Coll Cardiol. 2005;45(8):1193-1200

0.15mm

0.60mm

End points Endeavor

(n=1162)

Cypher

(n=1170)

p

The Endeavor stent: SORT OUT III Study

(n=1162) (n=1170)

MACE (Cardiac death, MI, TVR) 113 (10.0%) 53 (5.0%) <0.0001

TLR 71 (6.0%) 20 (2.0%) <0.0001

All cause mortality 51 (4.0%) 32 (3.0%) 0.035

RasmunsenRasmunsen K.K. et.al. “et.al. “Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents

in routine clinical care (SORT OUT III): a randomised controlled superiority trial” JACC 2006; 46” JACC 2006; 46: :

24402440--4747

Biolimus vs Sirolimus eluting stents

5 years follow up of the LEADERS Trial5 years follow up of the LEADERS Trial857 857 ptspts with BES vs. 850 with SESwith BES vs. 850 with SES

P. P. SerruysSerruys, TCT 2012, TCT 2012

DES: Different approaches

Αντίδραση υπερευαισθησίας

J. Nebeker et al. (JACC. 2006;47:175-181)

Paclitaxel vs. Everolimus eluting stents2 years follow up of the SPIRIT IV Trial2 years follow up of the SPIRIT IV Trial

2458 2458 ptspts with EES vs. 1229 with PESwith EES vs. 1229 with PES

Stone G. et Stone G. et al “2 year follow up from the SPIRIT IV al “2 year follow up from the SPIRIT IV Trial”Trial”J Am Coll Cardiol 2011:28;58(1):19-25

EES vs. SES: SORT OUT IV Trial1390 1390 ptspts (1805 lesions) with EES vs. 1384pts (1779 lesions) with SES(1805 lesions) with EES vs. 1384pts (1779 lesions) with SES

Jensen L. et Jensen L. et al al Circulation.2012; 125: 1246-1255

Less ST with Everolimus

eluting stents

4 years Registry, 12339 4 years Registry, 12339 ptspts::

4212 4212 lsnslsns EES EES -- 4308 PES 4308 PES -- 3819 SES 3819 SES

RaberRaber L. et L. et al “al “Very Late Coronary Stent Thrombosis of a Newer-Generation Everolimus-Eluting

Stent Compared With Early-Generation Drug-Eluting Stents” Circulation.2012; 125: 1110-1121

Lower risk of cardiac death/MI with Lower risk of cardiac death/MI with

EES compared with PES (hazard EES compared with PES (hazard

ratio:0.65; 95% confidence interval, ratio:0.65; 95% confidence interval,

0.560.56––0.75;0.75; PP<0.0001)<0.0001)

ZES Resolute vs. EES

13 months follow up of the RESOLUTE All 13 months follow up of the RESOLUTE All ComersTrialComersTrial1140 1140 ptspts with ZES vs. 1152 with EESwith ZES vs. 1152 with EES

0.15mm

0.06mm

SerruysSerruys P. et P. et al “al “Comparison of Zotarolimus-Eluting and Everolimus-Eluting Coronary Stents” ”

N Engl J Med 2010; 363:136-146

0.06mm

New DES have to present convincing data

S. Windecker et al. (PCR 2013)

The CoStar stent: PISCES Study

P. Serruys et al. ( JACC 2005;46:253-260 )

Lowest in-stent late loss (0.38 mm, and 0.30 mm, p <0.01) and volume

obstruction (8% and 5%, p <0.01) in the 30-day release groups (10µg, 30µg).

8.6% MACE for DES: death 0.5%, myocardial infarction 2.7%, and TLR 5.3%.

•DES are complex devices with different characteristics and

should be judged from their results as regards efficacy and

safety

CONCLUSIONS

•There are second generation DES that have shown superiority

compared to first generation (Cypher or Taxus) stents

•DES technology will continue to evolve aiming to devices with

higher efficacy and safety

Thank you for your attention!Thank you for your attention!

www.mathetinkardiasou.grwww.mathetinkardiasou.gr

The Endeavor stent: More safe?

ZES SES PES

1 year follow up of the ZEST Trial1 year follow up of the ZEST Trial2645 2645 ptspts randomized to ZES, SES, PESrandomized to ZES, SES, PES

Park D.Park D. et.al. “et.al. “Comparison of Zotarolimus-Eluting Stents With Sirolimus- and Paclitaxel-Eluting

Stents for Coronary Revascularization : The ZEST (Comparison of the Efficacy and Safety of

Zotarolimus-Eluting Stent with Sirolimus-Eluting and PacliTaxel-Eluting Stent for Coronary

Lesions) Randomized Trial” JACC 2010; 56” JACC 2010; 56: 1187: 1187--95 95

An unsuccessful trial: SCORE

E. Grube et al. ( JACC 2004;44:1368-1372 )

QuaDDS stent

7,4% restenosis rate (32,7%),

but 10,3% stent thrombosis (0,7%)

Loss of side branches after

Taxus stent implantation

G. Stone, TCT 2005

2 years follow up of the COMPARE Trial2 years follow up of the COMPARE Trial897pts (1286 lesions) with EES vs. 903pts (1294 897pts (1286 lesions) with EES vs. 903pts (1294 lsnslsns) with PES) with PES

Smits P. et Smits P. et al “2 year follow up al “2 year follow up of a Randomized Controlled Trial of EES and PES for Coronary

Revascularization in Daily Practice” J Am Coll Cardiol. 2011;58(1):11-18

Paclitaxel vs. Everolimus eluting stents

2 years follow up of the SPIRIT III Trial2 years follow up of the SPIRIT III Trial669 lesions with EES vs. 333 with PES669 lesions with EES vs. 333 with PES

0.28mm

Stone G. et Stone G. et al Randomized Comparison of al Randomized Comparison of EverolimusEverolimus--Eluting and Eluting and PaclitaxelPaclitaxel--Eluting Eluting

StentsStents. Circulation. 2009;119:680. Circulation. 2009;119:680--686686

Treatment with Treatment with EverolimusEverolimus stent resulted in a trend toward fewer restent resulted in a trend toward fewer re--

interventions (TLR), fewer MIs and reduction in the composite of death/MI interventions (TLR), fewer MIs and reduction in the composite of death/MI

(4.8% vs. 8.1%, relative risk: 0.60, 95% CI:(4.8% vs. 8.1%, relative risk: 0.60, 95% CI: 0.36 to 0.99, p=0.055)0.36 to 0.99, p=0.055)

0.14mm

0.28mm

Offsetting impact of ST and restenosis

on the occurrence of death/MI

G. Stone et.al. “Offsetting impact of thrombosis and restenosis on the occurrence of death and

myocardial infarction after paclitaxel-eluting and bare metal stent implantation ”

Circulation 2007 Jun 5;115(22):2842-7

Manufacturer Name Drug Stent material Polymer Status

Abbott ZoMaxx Zotarolimus Tantalum/St steel Durable —

Sorin Janus Tacrolimus Stainless steel None CE

Conor CoStar Paclitaxel Cobalt chromium Bioabsorbable CE


Conor CoStar Paclitaxel Cobalt chromium Bioabsorbable CE

Guidant Xience V Everolimus Cobalt chromium Durable CE

Medtronic Endeavor Zotarolimus Cobalt chromium Durable CE

Terumo Nobori Biolimus-A9 Stainless steel Bioabsorbable —

The bioabsorbable stent: ABSORB

Study

6-month follow-up 26 lesions

In-stent diameter stenosis (%) 27

In-stent late loss (mm) 0.44

In-stent restenosis (%) 11.5

Serruys P. American College of Cardiology 2007 Scientific Sessions; March 24, 2007.

In-stent restenosis (%) 11.5

A stent A stent made from a polylactic acid (PLA) backbone, with an everolimus/PLA made from a polylactic acid (PLA) backbone, with an everolimus/PLA

coating coating expected toexpected to dissolve dissolve completely completely after 12after 12--18 month18 monthss

LLate loss and restenosis were greater than with current ate loss and restenosis were greater than with current DESDES, , probably due toprobably due to the the

15% shrinkage seen with the new stent15% shrinkage seen with the new stent


DES proven superior to BMS and DES proven superior to BMS and

used extensively in everyday practice used extensively in everyday practice

in USA & Europein USA & Europe

Cypher stentCypher stent

Taxus stentTaxus stent

DES proven superior to BMSDES proven superior to BMS

DES proven nonDES proven non--inferior to either inferior to either

Cypher or Taxus Cypher or Taxus

DES tested in clinical studies and/or DES tested in clinical studies and/or

used in everyday practice in Europeused in everyday practice in Europe

Taxus vs. Cypher stent: long lesions

LLesionsesions ≥≥ 24mm 24mm treatedtreated withwith longlong CypherCypher (223)(223), Taxus, Taxus (194), (194), oror BMBM stentsstents

Mean Lesion length treated with Cypher stent: 36.0 Mean Lesion length treated with Cypher stent: 36.0 ±± 14.9mm14.9mm

Mean Lesion length treated with Taxus stent: 36.3 Mean Lesion length treated with Taxus stent: 36.3 ±± 14.5mm 14.5mm

6 month in6 month in--segment restenosis rates were higher for Taxus (21.3%) than segment restenosis rates were higher for Taxus (21.3%) than

Y. Kim et.al. “Comparison of sirolimus-eluting stent, paclitaxel-eluting stent, and bare metal stent in

the treatment of long coronary lesions” Cath Cardiovasc Interv 2006;67(2):181-187

6 month in6 month in--segment restenosis rates were higher for Taxus (21.3%) than segment restenosis rates were higher for Taxus (21.3%) than

Cypher group (9.3%, p=0.002)Cypher group (9.3%, p=0.002)

6 month 6 month MACE rate was similar: 13.0% for Cypher and 15.7% for Taxus MACE rate was similar: 13.0% for Cypher and 15.7% for Taxus

stentstent

End point XIENCE V Taxus P

In-segment late loss (mm) 0.14 0.28 <0.001 (noninferiority)

0.004 (superiority)

In-stent late loss (mm) 0.16 0.31 0.006

The Xience V stent: SPIRIT III Study

Stone G. American College of Cardiology 2007 Scientific Sessions. March 24, 2007

In-stent late loss (mm) 0.16 0.31 0.006

In-segment binary

restenosis (%)

4.7 8.9 0.07

Target vessel failure 7.2 9.0 <0.0001 (noninferiority)

MACE 4.6 8.1 0.025 (superiority)

PES vs. SES: REALITY study

MC. Morice. April 2005. tctmd.com

Drug -eluting stents Are they all equal? · Kandzari D.Kandzari D.et.al. “ et.al. “Comparison...

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