Comparison of Zotarolimus-eluting d E li l ti Cand Everolimus-eluting Coronary

Stents

2 Years ResultsRESOLUTE All Comers Trial

Patrick W. Serruys MD, PhD on behalf of the InvestigatorsgThoraxcenter, Erasmus MC, Rotterdam, the Netherlands

T t i l L l 4Tutorial arena, Level 49:30-40, April 28, 2011

E-pub ahead of print

Background

• 1st generation DES reduced rates of restenosis, ge e at o S educed ates o este os s,although long-term follow-up revealed safety concerns over very late stent thrombosis

• 2nd generation devices utilize new stent platforms and more biocompatible polymers

• Previous DES trials were largely performed in on-label indications, restricting wider

fapplicability of their results to routine clinical practice

• Presently there are no randomizedcomparisons between 2nd generation DES followed out to 2 yearsDES followed out to 2 years

RESOLUTE All Comers Trial Design

Any Patient With SymptomaticAny Patient With Symptomatic

17 European sites2300 ti t 1 1 d i ti

y y py y pCoronary Artery DiseaseCoronary Artery Disease

Resolute StentResolute Stentn = 1150n = 1150

Xience V StentXience V Stentn = 1150n = 11502300 patients 1:1 randomizationn = 1150n = 1150

1:4n = 1150n = 1150

1:4Angio f/uAngio f/un = 230n = 230

Angio f/uAngio f/un = 230n = 230

Clinical endpoints30d 6mo 4yr3yr2yr12mo 13mo 5yr

n = 230n = 230 n = 230n = 230

QCA 460 (20%)OCT 50 (2%)

yyy y

Primary Endpoint: Primary Endpoint: •• Target Lesion Failure (composite of cardiac death, target vessel MI & clinically driven TLR) at 12moTarget Lesion Failure (composite of cardiac death, target vessel MI & clinically driven TLR) at 12moSecondary Endpoints:Secondary Endpoints:•• Clinical: Patient composite of any death, any MI, & any repeat revascularisationClinical: Patient composite of any death, any MI, & any repeat revascularisation•• QCA (powered): 13QCA (powered): 13--month inmonth in--stent % diameter stenosisstent % diameter stenosis•• QCA: % diameter stenosis, late loss, and binary restenosisQCA: % diameter stenosis, late loss, and binary restenosisDrug Therapy:Drug Therapy: ASA and clopidogrel/ticlopidine ASA and clopidogrel/ticlopidine >> 6mo (per guidelines)6mo (per guidelines)

Patient Flow Chart

P ti t E ll dP ti t E ll dPatients EnrolledPatients EnrolledN = 2292N = 2292

RandomizedResolute (RResolute (R--ZES)ZES)N = 1140N = 1140

Xience V (EES)Xience V (EES)N = 1152N = 1152

1 Yr Clinical Follow1 Yr Clinical Follow--upup 1 Yr Clinical Follow1 Yr Clinical Follow--upupn = 1130n = 113099.1%99.1%

n =1138n =113898.8%98.8%

2 Yr Clinical Follow2 Yr Clinical Follow--upupn =1121n =112198 3%98 3%

2 Yr Clinical Follow2 Yr Clinical Follow--upupn = 1128 n = 1128

97 9%97 9%98.3%98.3% 97.9%97.9%

Baseline Patient Characteristics

Variable, %R-ZES

(N = 1140 pts)EES

(N = 1152 pts)Variable, % (N 1140 pts) (N 1152 pts)Age, years (Mean+SD) 64.4±10.9 64.2±10.8Men 76.7 77.2Diabetes mellitus 23.5 23.4

Insulin treated 8.4 7.1 Arterial hypertension 71 1 71 3Arterial hypertension 71.1 71.3 Hyperlipidemia 64.0 67.7 Current smoker 26.5 26.5 Premature CAD in first degree relative 34.1 36.7 Prior myocardial infarction 28.9 30.4 Prior percutaneous coronary intervention 31 8 32 1Prior percutaneous coronary intervention 31.8 32.1 Prior coronary artery bypass grafting 10.0 9.5Stable angina 33.5 36.1 Unstable angina 19.4 18.9 Acute myocardial infarction ≤72 hours 28.9 28.8

Baseline Patient Characteristics

Variable, %R-ZES

(N = 1140 pts)EES

(N = 1152 pts)Variable, % (N 1140 pts) (N 1152 pts)Left ventricular ejection fraction <30% 2.8 2.1Multi-vessel disease 58.4 59.2 Target vessel location (per patient)Target vessel location (per patient)

Left main 2.2 2.5Left anterior descending 52.6 48.6 L ft i fl 33 0 32 9Left circumflex 33.0 32.9 Right coronary 37.3 41.3 Bypass graft 2.5 2.4

Number of treated lesions per patient 1.5±0.7 1.5±0.8SYNTAX score 15±9 15±9≥1 small vessel (RVD ≤2.75 mm) 67.8 67.4≥1 lesion length >18 mm 18.2 21.2≥1 bifurcation/trifurcation 16.9 17.7≥1 total occlusion 16.3 17.2≥1 total occlusion 16.3 17.2≥1 In-stent restenosis 8.1 8.0Off-label use 67.0 65.6

Clinically Driven Target Lesion Revascularization Through 2 Yearsg

15%s EESR-ZES Log rank P = 0.567515%

Even

ts EESR ZES g95% CI = 0.6% [-1.3%, 2.4%]

10%

ence

of

5%ve In

cide

5.7%5 2%5%

mul

ativ 5.2%

0%0 180 360 540 720

Cum

Time after Initial Procedure (days)

Cardiac Death and Target Vessel MI Through 2 Yearsg

15%s EESR-ZES Log rank P = 0.541015%

Even

ts EESR ZES g95% CI = 0.7% [-1.4%, 2.7%]

10%

ence

of

5%ve In

cide 7.0%

6.2%5%

mul

ativ

0%0 180 360 540 720

Cum

Time after Initial Procedure (days)

Components of Target Lesion Failure

Cardiac Death (%)

P = 0.58

TV-MI (%)

P = 0.84

ID-TLR (%)

P = 0.580.4% [-0.9%, 1.6%] 0.2% [-1.5, 1.9%] 0.6% [-1.3%, 2.4%]

4.7 4.55.7

5.1

2.6 2.2

R-ZES EES R-ZES EES R-ZES EESR ZES EES R ZES EES R ZES EESn = 1121 n = 1128n = 1121 n = 1128 n = 1121 n = 1128

Cumulative Incidence for Cardiac Death/TVMI and Clinically Driven TLR (TLF)y ( )

)

EES R-ZESP = 0.7304

95% CI = 0.5% [-2.1%, 3.1%]ents

(%)

20%

95% CI 0.5% [ 2.1%, 3.1%]

e of

Eve

11 2%

15%

ncid

ence 11.2%

10.7%10%

ativ

e In

5%

Cum

ul

0%0 180 360 540 720

Time after Initial Procedure (days)0 180 360 540 720

Patient Composite Endpoint Through 2 Years (All Death, All MI, Any ( , , yRevascularizations)

20.6%20%

Even

ts20.6%20.5%EESR-ZES

nce

of E 15%

Log rank P = 0.958

Inci

den

10%Log rank P 0.958

95% CI = 0.1% [-3.2%, 1.9%]

ulat

ive

5%

0%Cum

0 180 360 540 720Time after Initial Procedure (days)

0 180 360 540 720

Composite Clinical Endpoint Results at 2 Yearsat 2 Years

Device Oriented Patient Oriented20 6 20 5

P = 0.74 P = 1.00

20.6 20.5

11.2 10.7

R-ZES EESn = 1121 n = 1128

R-ZES EESn = 1121 n = 1128

TLF (%)(Cardiac Death, Target Vessel MI, TLR)

All Event Composite (%)(All Death, All MI, Any Revasc)

Definite or Probable Stent Thrombosis at 2 Years

% (n) R-ZESN = 1140

EESN = 1152 95% CI P value

at 2 Years

( ) N = 1140 N = 1152

Early (≤30 days)

1.1%(12)

0.5%(6) 0.5% [-0.2%, 1.3%] 0.16(≤30 days) (12) (6)

Late (31-360 days)

0.6%(7)

0.2%(2) 0.4% [-0.1%, 1.0%] 0.11

Def/prob ST at 1 year

1.6%(18)

0.7%(8) 0.9% [0.0%, 1.8%] 0.05

Very Late (>360 days)

0.3%(3)

0.3%(3) 0.0% [-0.4%, 0.4%] 1.00

Def/prob ST at 2 years

1.9%(21)

1.0%(11) 0.9% [-0.1%, 1.9%] 0.08

Stent Thrombosis (ARC Definite /Probable) Through 2 Years) g

L k P 0 07715%

Even

ts EESR-ZES Log rank P = 0.07795% CI = 0.9% [-0.1%, 1.9%]

nce

of E

10%

Inci

den

mul

ativ

e 5%

1 9%

0%Cum

0 180 360 540 720

1.9%1.1%

Time after Initial Procedure (days)0 180 360 540 720

DAPT* Compliance to 2 Years

% patients on DAPT at R ZES EES P valueon DAPT at R-ZES EES P value

30 days 93.8 94.6 0.43

180 days 93.1 93.3 0.93y

360 days 84 1 83 8 0 91360 days 84.1 83.8 0.91

720 d 18 6† 18 1† 0 78720 days 18.6† 18.1† 0.78

* Aspirin and (Clopidogrel or Ticlopidine) Aspirin and (Clopidogrel or Ticlopidine)† Majority on DAPT considered complex or ACS at time of procedure

Conclusion

B th th R l t ZES d th Xi V• Both the Resolute ZES and the Xience V EES were associated with a relatively low f f d t i thifrequency of adverse events even in this complex, all-comers patient population through 2 yearsthrough 2 years

• The new generation Resolute ZES gremained clinically equivalent to the Xience V EES in this predominantly p ycomplex patient population through 2 years