meredith ● evolve primary endpoint ● tct 2011 ● san francisco, ca slide 1 meredith ● evolve...

Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 1Meredith ● EVOLVE overview ● TCT 2010 ● Washington, DC Slide 1

Clinical and Angiographic Outcomes of the EVOLVE Trial: A

Randomized Evaluation of a Novel Bioabsorbable Polymer-Coated,

Everolimus-Eluting Coronary Stent

Ian T. Meredith, Stefan Verheye, Christophe L. Dubois, Joseph Dens,

Jean Fajadet, Didier Carrié, Simon Walsh, Keith G. Oldroyd, Olivier Varenne, Seif El-Jack, Raul Moreno, Anita A. Joshi,

Dominic J. Allocco, Keith D. Dawkins

Meredith ● EVOLVE Primary Endpoint ● TCT 2011 ● San Francisco, CA Slide 2

Introduction

• Durable polymer coatings on drug-eluting stents have been associated with chronic inflammation and impaired healing.

• Reduced Polymer Load• Short-term Polymer

Exposure

• Reduce DAPT duration• Reduce risk with DAPT

interruption• Decrease stent thrombosis

may

Potential advantages of bioabsorbable polymer stents:


SYNERGY Stent

Bioabsorbable polymer (PLGA)

Applied only to the abluminal surface (rollcoat)

Thin strut (0.0029”) PtCr Stent

Durable PermanentPolymer

+Drug

360° AroundStent

PLGA BioabsorbablePolymer

+Everolimus

on Abluminal Side of Stent

Abluminal Bioabsorbable Polymer

Current Durable Polymer

Abluminal Bioabsorbable Polymer


SYNERGY Polymer Mass

Polymer resorption is complete within 4 months

PLGA mass assessed in explanted stent and adjacent tissue

Time (Days)

Pol

ymer

Mas

s R

emai

ning

(%

)


EVOLVE Trial

• Primary Objective– To compare the bioabsorbable polymer SYNERGY

Everolimus-Eluting Coronary Stent System to the permanent polymer PROMUS Element Stent for the treatment of de novo atherosclerotic lesions

• Test Devices– SYNERGY (everolimus dose and release profile similar to

PROMUS Element)

– SYNERGY ½ Dose (half the everolimus dose and similar release profile to PROMUS Element)

• Control Device– PROMUS Element


EVOLVE Study Design

Randomized 1:1:1 at 29 sites(EU, Australia, New Zealand)

SYNERGYN=94

SYNERGY ½ DoseN=99

PROMUS ElementN=98

Single-blind, noninferiority designPrimary Clinical Endpoint: TLF (TV-CD, TV-MI, or TLR) at 30 daysPrimary Angiographic Endpoint: In-stent late loss at 6 months

Patients with de novo native coronary lesions≤ 28 mm in length, RVD ≥2.25 mm ≤ 3.5, %DS>50

(excluded LM disease, CTO, AMI or recent MI)


Sample Size & Power Calculation

Expected rate for both groups = 0.14 ± 0.47 mm*

Non-inferiority margin (Δ) = 0.20

Test significance level () = 0.048 (1-sided)

Power (1) = approximately 0.85

Expected rate of attrition = 20%

N = 291 patients (97 per group at 1:1:1 ratio)

* From SPIRIT III (9-month endpoint)

If the P value from the one-sided Student test is <0.048, it will be concluded

that SYNERGY is non-inferior to PROMUS Element

Primary Angiographic Endpoint: 6-month in-stent Late Loss


EVOLVE Trial Support

Co-PrincipalInvestigators

Core Labs

Clinical EventsCommittee

Data MonitoringCommittee


Top 10 Enrolling SitesEVOLVE Centers


Patient Flow

6-Month Follow-upClinical: 99.9% (97/98)Angio: 96.9% (95/98)

SYNERGY(N=94)

PROMUS Element(N=98)

No 6-Month f/u (n=1)Withdrew consent: 0Missed 6 mo visit: 1


No 6-month f/u (n=1)Withdrew consent: 0Missed 6 mo visit: 1


SYNERGY ½ Dose(N=99)

No 6-month f/u (n=3)Withdrew consent: 0Missed 6 mo visit: 3

All Patients Randomized(N=291)


Baseline DemographicsSYNERGY

½ DoseN=99

SYNERGYN=94

PROMUSElement

N=98P valueP value

Intent-to-treat; P values are versus PROMUS Element; *medically treated


Baseline Lesion Characteristics SYNERGY

½ DoseN=99

SYNERGYN=94

P valueP value

Lesion characteristics evaluated by QCA.Intent-to-treat; P values are versus PROMUS Element

PROMUSElement

N=98


Procedural CharacteristicsSYNERGY

½ DoseN=99

SYNERGYN=94

PROMUSElement

N=98P valueP value

aStudy stents in target lesion onlybDefined as %DS<30 with TIMI flow 3 and no in-hospital MI, TVR, or cardiac deathcDefined as successful delivery and deployment of the study stent to the target vessel without balloon rupture or stent embolizationIntent-to-treat; P values are versus PROMUS Element


Post-Procedure AngiographicCharacteristics

SYNERGY½ DoseN=99

SYNERGYN=94

PROMUSElement

N=98P valueP value

*By QCAValues are mm or percentIntent-to-treat; P values are versus PROMUS Element


Late Loss at 6 Months

SYNERGY½ Dose

Late

loss

, m

m

SYNERGY

SYNERGY½ Dose

Diff

eren

ce (

SY

NE

RG

Y –

PR

OM

US

)

Late Loss at 6 Months Difference and 95.2% UCBNoninferiority

Threshold

Noninferiority is proven because the upper 95.2% confidence bound of the difference in 6-month late loss is <0.20 for both SYNERGY stents

P<0.001

P<0.001

P=0.19*

P=0.56*

PROMUSElement

SYNERGY

Intent-to-treat; *P values for superiority comparison


SYNERGY½ DoseN=99

SYNERGYN=94

PROMUSElement

N=98P valueP value

Assessed by QCAValues are mm or percentIntent-to-treat; P values are versus PROMUS Element

Angiographic Outcomes at 6 mo

In-stent values


Death and MI at 6 MonthsP

atie

nts,

%

All P=N.S.

AllDeath

CardiacDeath

NoncardiacDeath

AllMI

Q-Wave Non-Q-Wave

PROMUS Element

SYNERGY ½ Dose

SYNERGY

The cause of the noncardiac death in the SYNERGY group was a motor vehicle accident at 191 days post-procedure.Intent-to-treat; P values are versus PROMUS Element (Fisher exact test)


Revasc and ST at 6 MonthsP

atie

nts,

%

All P=N.S.

Intent-to-treat; P values are versus PROMUS Element (Fisher exact test)

TVR TLR Non-TLRTVR

StentThrombosis

PROMUS Element

SYNERGY ½ Dose

SYNERGY


Target Lesion Failure

PROMUSElement

SYNERGY SYNERGY½ Dose

Pat

ient

s, %

P=1.00

P=0.72

Intent-to-treat; P values are versus PROMUS Element (Fisher exact test)

PROMUSElement

SYNERGY SYNERGY½ Dose

Pat

ient

s, %

30 days 6 Months

P=0.49

P=0.25


Limitations

• The study only included patients with relatively simple de novo lesions– Patients with AMI, stroke, CTO, bifurcation, LMCA lesion, SVG

lesion, ostial lesions, or lesions with thrombus or excessive tortuosity or angulation were excluded

• The study was not powered to detect differences in clinical event rates

• The study was not designed to assess the risk of thrombosis or the required duration of dual antiplatelet therapy with SYNERGY– Two additional studies planned with adequate power to

• Assess clinical event rates

• Assess long vs short duration of DAPT


Conclusions

• In this prospective, randomized, multicenter, First Human Use trial, the two dose formulations of the SYNERGY stent were non-inferior to the PROMUS Element stent for the primary angiographic endpoint of in-stent late loss at 6 months. – Clinical events were low and comparable with no stent

thromboses in any group.

• These results support the safety and efficacy of the novel abluminal bioabsorbable polymer SYNERGY everolimus-eluting stent for the treatment of patients with de novo coronary artery disease.

• Additional research is needed to evaluate clinical event rates and the potential for dual antiplatelet therapy reduction with this novel stent.


Thank you to the EVOLVE Site Investigators

meredith ● evolve primary endpoint ● tct 2011 ● san francisco, ca slide 1 meredith ● evolve...

Documents