Samsung Medical Center Sungkyunkwan University School of Medicine Hyeon-Cheol Gwon, Joo Yong Hahn, Young Bin Song, Kyung Woo Park, Yang Soo Jang, Hyo-Soo

Samsung Medical CenterSungkyunkwan UniversitySchool of Medicine

Hyeon-Cheol Gwon, Joo Yong Hahn, Young Bin Song,Kyung Woo Park, Yang Soo Jang, Hyo-Soo Kim,On behalf of the EXCELLENT Trial Investigators

Samsung Medical Center, Sungkyunkwan University School of Medicine


Background: The current guideline recommends 12 months or longer duration after the implantation of drug-eluting stent (DES), not based on any prospectively randomized data.. Prolonged dual antiplatelet therapy has been one of the major morbidities after the procedure. In this prospective randomized trial, we compared the efficacy and safety of 6-month versus 12-month dual antiplatelet therapy.Methods: This study is a prospective, randomized, open label, multi-center trial with a 2×2 factorial design according to the type of stent (everolimus eluting stent vs. sirolimus eluting stent) and the duration of dual antiplatelet therapy (DAT: 6 vs. 12 months). Aspirin was used indefinitely. The primary endpoint was 12-month target vessel failure (TVF), a composite of cardiovascular death, myocardial infarction, and target vessel revascularization. The trial design has been published previously and the trial is registered at clinicaltrials.gov (NCT00698607).Results: A total of 1443 patients from 19 Korean centers were randomized 1:1 either to 6-month (6-month group, N=722) or to 12-month duration of dual antiplatelet therapy (12-month group, N=721). There were no significant differences in baseline characteristics between 2 groups. Twelve-month TVF rate was not significantly different between 2 groups (6-month group 4.7%, 12-month group 4.4%, p=0.721). Six-month group was significantly non-inferior to 12-month group with regard to the risk of TVF (p for non-inferiority = 0.0031, predefined non-inferiority margin 4.0%). Non-inferiority was shown to be significant in everolimus-eluting stent subgroup (p=0.0029) Conclusions: Six-month DAT is non-inferior to 12-month DAT with regard to the risk of TVF at 12 months after DES implantation. A larger-scale randomized controlled trial is required to test the impact of shorter duration of clopidogrel therapy on the hard endpoints of death, MI, or stent thrombosis.


Prospective, open label, two-arm, randomized multi-center trial

Clinical

Angiographic

Primary clinical endpoint evaluation

Co-primary angiographicendpoint evaluation

DAT 6 monthsDAT 6 monthsN=722N=722

DAT 12 monthsDAT 12 monthsN=721N=721

1443 Patients Matching Enrollment Criteria

EESEESN=540N=540

SESSESN=182N=182

EESEESN=539N=539

SESSES

N=182N=182

Percutaneous Coronary InterventionPercutaneous Coronary Intervention

2x2 factorial design

2x2 factorial design

Am Heart J 2009 May;157:811-817.e1www.clinicaltrials. gov (NCT00698607).


Variables ― no. (%)

6-mo DAT(N=716)

12-mo DAT(N=712)

RR (95% CI) p-value

Total death 4 (0.6) 7 (1.0) 0.57 (0.17-1.94) 0.359

Cardiac death 2 (0.3) 3 (0.4) 0.66 (0.11-3.97) 0.650

MI 13 (1.8) 8 (1.1) 1.63 (0.67-3.95) 0.277

MI of target vessel 12 (1.7) 5 (1.0) 1.72 (0.67-4.39) 0.253

CVA 3 (0.4) 5 (0.7) 0.60 (0.14-2.50) 0.473

TLR 17 (2.4) 19 (2.7) 0.89 (0.46-1.72) 0.723

TVR 22 (3.1) 22 (3.2) 0.95 (0.52-1.72) 0.865

Any revascularization 41 (5.7) 43 (6.0) 0.95 (0.61-1.47) 0.802

Stent thrombosis 6 (0.8) 3 (0.4) 2.00 (0.50-8.02) 0.320

Any bleeding 4 (0.6) 10 (1.4) 0.39 (0.12-1.26) 0.105

TIMI major bleeding 2 (0.3) 4 (0.6) 0.50 (0.09-2.72) 0.409

Safety endpoint 24 (3.4) 22 (3.1) 1.09 (0.60-1.96) 0.779

TVF 34 (4.7%) 31 (4.4%) 1.10 (0.67-1.80) 0.721

MACCE 54 (7.5) 60 (8.4) 0.89 (0.60-1.30) 0.537

Safety endpoint: death, MI, CVA, stent thrombosis, or TIMI major bleedingTVF: cardiac death, MI, or TVRMACCE: death, MI, CVA, or any revascularization

(Chi-square test)(Chi-square test)


Non-inferior

-1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 %

6-mo DAT6-mo DAT(N=1067)(N=1067)

5.2±0.8%5.2±0.8%

12-mo DAT12-mo DAT(N=361)(N=361)

4.3±0.8%4.3±0.8%

DifferenceDifference

p=0.426p=0.426

DifferenceDifference

p=0.426p=0.426

Non-inferiorityNon-inferiority

p=0.0031p=0.0031

1˚ Endpoint

(Kaplan-Meier Analysis)(Kaplan-Meier Analysis)

Cumulative proportional TVF estimate at 1 year

0.9% 3.6%

Pre-specified Pre-specified non-inferiority non-inferiority

marginmargin4.0%4.0%

Pre-specified Pre-specified non-inferiority non-inferiority

marginmargin4.0%4.0%

Upper 1-sided 97.5% CIDifference


Months after initial procedure

Cu

mu

lati

ve in

cid

ence

rat

e (%

)

Patient Number at Risks

6-month 722 707 701 697 681

12-month 721 710 699 698 680

1˚ Endpoint

P=0.507HR = 1.17 (95% CI 0.73-1.89)

4.7%

4.4%

6-mo DAT

12-mo DAT


(Kaplan-Meier Analysis)(Kaplan-Meier Analysis)

Cumulative proportional TVF estimate at 1 year

-1 0 1 2 3 4 5 6

6-mo DAT6-mo DAT(N=182)(N=182)

5.0±1.6%5.0±1.6%

12-mo DAT12-mo DAT(N=182)(N=182)

2.2±1.1%2.2±1.1%

Non-Non-inferiorityinferiority

p=0.268p=0.268

97.5%

-1 0 1 2 3 4 5 6

6-mo DAT6-mo DAT(N=540)(N=540)

5.2±1.0%5.2±1.0%

12-mo DAT12-mo DAT(N=539)(N=539)

5.1±1.0%5.1±1.0%

Non-Non-inferiorityinferiority

p=0.0029p=0.0029

Everolimus-eluting StentEverolimus-eluting Stent Sirolimus-eluting StentSirolimus-eluting Stent

0.1% 2.9% 2.2% 6.6%

Pre-specified non-inferiority margin: 4.0%

Upper 1-sided97.5% CI

Difference



6-mo 540 531 528 524 511

12-mo 539 531 524 521 505

Everolimus-eluting StentEverolimus-eluting Stent Sirolimus-eluting StentSirolimus-eluting Stent


6-mo 182 176 176 174 171

12-mo 182 179 179 178 176

p=0.914HR = 1.03 (0.61-1.75)

p=0.168HR = 2.29 (0.71-7.43)

6-mo DAT

12-mo DAT

4.6%

5.0%

4.9%

2.2%


Six-month DAT is non-inferior to 12-month DAT with regard to the risk of target vessel failure at 12 months after DES implantation.

In particular, the EES subgroup showed very similar event rates between the 6-month and 12-month DAT groups.

A larger-scale randomized controlled trial is required to test the impact of shorter duration of clopidogrel therapy on the hard endpoints of death, MI, or stent thrombosis.

Documents

Samsung Medical Center Sungkyunkwan University School of Medicine Hyeon-Cheol Gwon, Joo Yong Hahn, Young Bin Song, Kyung Woo Park, Yang Soo Jang, Hyo-Soo