Stents actifs: tous égaux?

Philip Urban

Hôpital de La Tour, Genève

31 janvier – 2 février 2018

The first clinical coronary stent, March 1986

Mrs. G.D. 1936 Lausanne, June 12, 1986

1991

2017

SYNTAX trial (Taxus PES) - 5 year ARC stent thrombosis (per patient)

P. Serruys, TCT 2012

The new generation of DES

SORT-OUT IV @ 4 years – Lisette Okkels Jensen

2774 patients

“All animals are equal, but some animals are more equal than others”

Mechanical properties of DES

• strut thickness

• longitudinal deformation

• radial force & recoil

• maximal expansion

• sidebranch access

• strut rupture

Byrne R et al. Eur Heart J 2015; 36: 3320–3331

Longitudinal distortion

John Ormiston – TCT 2014

John Ormiston – TCT 2014

Over-expansion capacity and stent design model Ng J et al Int J Cardiol 2016; 221:171-9

5,8 5,7 5,6 5,2

6 5,8

0

1

2

3

4

5

6

7

Ultimaster(3.5-4.0)

Synergy(4.0)

Xience (3.5-4.0)

Orsiro (3.5-4.0)

ResoluteOnyx (4.5-

5.0)

BiomatrixAlpha (3.5-

4.0)

Side branch access

Stent fracture with 2nd G DES Kim D-K, Busan, South Korea

TCT 2016

Incidence of stent fracture

• 1046 patients • FU for 3 years • Angio/IVUS/OCT

Stent fracture with 2nd G DES Kim D-K, Busan, South Korea

TCT 2016

Circulation 2014; 129:211

204 lesion from 149 autopsy studies

EES superior for ST, % uncovered struts, inflammation score

but comparable incidence of neoatherosclerosis

NEOATHEROSCLEROSIS

European Heart Journal 2016; 37: 1208–16

Ruptured neoatherosclerotic plaque

Do some of these differences impact clinical results, or are they

?

Bioscience 1063 BD-SES vs 1056 PP-EES

Pilgrim T et al Lancet 2014

NEXT (2y) 1617 BD-BES vs 1618 PP-EES

Natsuaki M et al JAMA 2014

non-inferiority trials

2nd G permanent vs. biodegradable polymer

120µ stainless steel + BD polymer vs. 81µ CoCr + Perm. polymer

60µ CocCr + BD polymer vs. 81µ CoCr + P polymer

BIOFLOW V Kandzari et al Lancet 2017; 390: 1843-52

• 1334 patients with SCAD or ACS randomized 2:1

• 60µ CoCr bio-resorbable polymer SES vs. 81µ CoCr durable polymer EES

• Primary EP = TLF = superiority of BP SES (driven by lower rates of MI)

“We defined peri-procedural

myocardial infarction according to

the protocol-defined modified ARC

criteria as a CK MB, if available,

or troponin measured within 48 h of

the interventional procedure

elevated > 3 x ULN”.

Interventional « front-running »

amount of data duration of FU

new features surrogate EPs

Is the coating really necessary?

1 Data on file at Biosensors Intl. 2 Tada et al Circ Cardiovasc Interv. 2010;3:174-183

BioFreedom™ Drug Coated Stent Selectively micro-structured surface holds

drug in abluminal surface structures

Proprietary Highly Lipophilic Limus drug

1 1

Advantages: • Avoid any possible polymer-related

adverse effects

• Rapid drug transfer to vessel wall

(98% within one month2)

• Good fit with short DAPT

Primary Endpoints and Major Bleeding at 1 Year

Urban P et al. N Engl J Med 2015;373:2038-47

Efficacy (cd-TLR) Safety (cardiac death, MI, ST)

0

90 180 270 390

Cu

mu

lative P

erc

en

tage

with

Eve

nt

3

6

9

12

Days 0

9.8%

5.1%

p for superiority < 0.001

HR 0.50, (95% CI = 0.37‒0.69)

%

12.9%

BMS DCS

0

90 180 270 390

3

6

9

12

Days 0

9.4%

HR 0.71, (95% CI = 0.56‒0.91)

p < 0.0001 for non-inferiority

p = 0.005 for superiority

15

%

Bleeding (BARC 3-5)

%

7.3%

7.2%

Interest for short DAPT ?

Trial stent type limus

kinetics patients experimental arm DAPT control arm

Status November 2017

SENIOR (1) Synergy EES 2nd G biodegradable

polymer slow

1200 elderly (>75)

1 month or 6 months (operator discretion)

BMS & same DAPT

DES superior to BMS for MACE

(efficacy + safety combined)

LEADERSFREE II BioFreedom DCS polymer-free fast 1200 HBR 1 month BMS arm of LEADERS

FREE follow-up

LEADERS FREE III CoCr BioFreedom Polymer-free fast 370 HBR 1 month DCS arm of

LEADERS FREE enrolling

YONSEI UNIVERSITY BioFreedom DCS polymer-free fast 3020

low risk SCAD 1 month

DES & 6-12 months DAPT

enrolling

ISAR DAPT Coroflex ISAR polymer-free matrix slow 906

low risk SCAD 3 months 6 months DAPT enrolling

ReCre8 Cre8 SES

polymer-free slow 1532

all-comers SCAD 1 month ACS 12 months

R-ZES same DAPT enrolling

EVOLVE SHORT DAPT Synergy EES 2nd G BD polymer slow 2000 HBR

3 months single arm trial enrolling

MASTER DAPT Ultimaster SES 2nd G BD polymer slow 4300 HBR

1 month guidelines enrolling

HOST-IDEA Orsiro SES vs. Coroflex ISAR

2ndG BD polymer vs. polymer-free matrix

slow slow

2132 SCAD (no OAC)

3 months 1 year DAPT enrolling

STOPDAPT-2 Xience EES 2nd G permanent polymer slow 3000 low/med risk

success PCI 1 month 1 year DAPT enrolling

COBRA-REDUCE Cobra PzF Polyzene-F

nanocoating na

840 on AVK or NOAC

2 weeks EES or R-ZES & 6 months DAPT

enrolling

POEM Synergy EES 2nd G BD polymer slow 1000 HBR 1 month single arm trial enrolling

XIENCE 90 (Xience Short DAPT)

Xience EES Permanent polymer Slow 2000 HBR 3 months Single arm trial enrolling

ONYX ONE Resolute Onyx DES

vs. BioFreedom DCS

Permanent polymer vs.Polymer-free

Slow vs. Fast

2000 HBR 1 month 1 month planned

2nd G DES: 14 other trials of short DAPT (3 months or less)

1) Varenne O et al. Lancet 2017 (on line)

Over the 16 years since their impact on ISR was first documented,

metallic polymer DES have improved very significantly

Whether biodegradable offer clinical benefit vs. current (“2nd G”)

permanent polymers is not yet determined

The incidence of late events induced by strut fractures and

neoathersclerosis could become reasons for preferring one DES over

another, but waiting for that information will require patience

Conclusions (I)

HBR patients are fast becoming the focus of major interest. They

require novel strategies that are adapted to their specific needs

The polymer-free BA-9 DCS (with 1 month DAPT) and the

biodegradable polymer EES (with 1 or 6 months DAPT) have been

shown to be superior to a BMS

All major DES are now being evaluated for their safety with short or

very short DAPT. The results of those trials may well become another

major reason for preferring one DES over another

Conclusions (II)

Thank you