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 Kim, On behalf of the EXCELLENT Trial Investigators Samsung Medical Center, Sungkyunkwan University School of Medicine

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 (NCT ). 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 = , 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.

Samsung Medical Center Sungkyunkwan University School of Medicine Prospective, open label, two-arm, randomized multi-center trial Clinical Angiographic Primary clinical endpoint evaluation Co-primary angiographic endpoint evaluation DAT 6 months N=722 DAT 12 months N= Patients Matching Enrollment Criteria EES N=540 SES N=182 EES N=539 SESN=182SESN=182 Percutaneous Coronary Intervention 2x2 factorial design Am Heart J 2009 May;157: e1 gov (NCT ).

Samsung Medical Center Sungkyunkwan University School of Medicine Variables ― no. (%) 6-mo DAT (N=716) 12-mo DAT (N=712) RR (95% CI)p-value Total death4 (0.6)7 (1.0)0.57 ( )0.359 Cardiac death2 (0.3)3 (0.4)0.66 ( )0.650 MI13 (1.8)8 (1.1)1.63 ( )0.277 MI of target vessel12 (1.7)5 (1.0)1.72 ( )0.253 CVA3 (0.4)5 (0.7)0.60 ( )0.473 TLR17 (2.4)19 (2.7)0.89 ( )0.723 TVR22 (3.1)22 (3.2)0.95 ( )0.865 Any revascularization41 (5.7)43 (6.0)0.95 ( )0.802 Stent thrombosis6 (0.8)3 (0.4)2.00 ( )0.320 Any bleeding4 (0.6)10 (1.4)0.39 ( )0.105 TIMI major bleeding2 (0.3)4 (0.6)0.50 ( )0.409 Safety endpoint24 (3.4)22 (3.1)1.09 ( )0.779 TVF34 (4.7%) 31 (4.4%)1.10 ( )0.721 MACCE54 (7.5)60 (8.4)0.89 ( )0.537 Safety endpoint: death, MI, CVA, stent thrombosis, or TIMI major bleeding TVF: cardiac death, MI, or TVR MACCE: death, MI, CVA, or any revascularization (Chi-square test)

Samsung Medical Center Sungkyunkwan University School of Medicine Non-inferior % 6-mo DAT (N=1067) 5.2±0.8% 5.2±0.8% 12-mo DAT (N=361) 4.3±0.8% 4.3±0.8% Differencep=0.426 Non-inferiorityp=0.0031Non-inferiorityp= ˚ Endpoint (Kaplan-Meier Analysis) Cumulative proportional TVF estimate at 1 year 0.9% 3.6% Pre-specified non-inferiority margin 4.0% Upper 1-sided 97.5% CI Difference

Samsung Medical Center Sungkyunkwan University School of Medicine Months after initial procedure Cumulative incidence rate (%) Patient Number at Risks 6-month month ˚ Endpoint P=0.507 HR = 1.17 (95% CI ) 4.7% 4.4% 6-mo DAT 12-mo DAT

Samsung Medical Center Sungkyunkwan University School of Medicine (Kaplan-Meier Analysis) Cumulative proportional TVF estimate at 1 year mo DAT (N=182) 5.0±1.6% 5.0±1.6% 12-mo DAT (N=182) 2.2±1.1% 2.2±1.1% Non- inferiority p=0.268 p= % mo DAT (N=540) 5.2±1.0% 5.2±1.0% 12-mo DAT (N=539) 5.1±1.0% 5.1±1.0% Non- inferiority p= p= Everolimus-eluting Stent Sirolimus-eluting Stent 0.1% 2.9% 2.2% 6.6% Pre-specified non-inferiority margin: 4.0% Upper 1-sided 97.5% CI Difference

Samsung Medical Center Sungkyunkwan University School of Medicine Patient Number at Risks 6-mo mo Everolimus-eluting Stent Sirolimus-eluting Stent Patient Number at Risks 6-mo mo p=0.914 HR = 1.03 ( ) p=0.168 HR = 2.29 ( ) 6-mo DAT 12-mo DAT 4.6% 5.0% 4.9% 2.2%

Samsung Medical Center Sungkyunkwan University School of Medicine  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.