ARCTIC-INTERRUPTION 2-year- Versus 1year Duration of Dual-Antiplatelet Therapy After DES implantation The randomized ARCTIC-Interruption Study JP Collet and G Montalescot for the ARCTIC investigators www.action-coeur.org ARCTIC: Assessment by a double Randomization of a Conventional antiplatelet strategy versus a monitoring-guided strategy for drug-eluting stent implantation and,of Treatment Interruption versus Continuation one year after stenting – ARCTIC-INTERRUPTION (NCT 00827411) COI Disclosure for Dr. Montalescot: Gilles Montalescot reports: research grants to the institution or consulting/lecture fees from Abbott Vascular, Accumetrics, AstraZeneca, Bayer, Biotronik, BMS, Boehringer-Ingelheim, Daiichi-Sankyo, Duke Institute, Eli Lilly and Company, Europa, Fédération Française de Cardiologie, Fondation de France, GSK, INSERM, Institut de France, Iroko, Lead-up, Menarini, Medtronic, Nanospheres, Novartis, Pfizer, ReCor Medical, Roche, Sanofi-Aventis, Stentys, Société Française de Cardiologie, Springer, The Medicines Company, The TIMI group, WebMD, and Wolters. 1

ARCTIC-INTERRUPTION design Rd #2 DAPT SAPT 6-18 more months of FU 1° EP: Death, MI, stroke, stent thrombosis, urg. revasc.

Randomized vs. Non-Randomized Age - median 63 64 Diabetes - % 33 40* Prior PAD- % 10 14* Prior PCI - % 41 45 Prior CABG - % 7 Proton pump inhibitors - % 31 Drug-eluting stent implanted - % 99 95* * p<0.05

DAPT vs. SAPT: Baseline characteristics Age - median 64 Diabetes - % 36 37 Prior MI - % 31 30 Prior PCI - % 43 40 Prior CABG - % 7 6 Clopidogrel - % 90 Clopidogrel 150 mg - % 10 14 Prasugrel - % 8.5 Proton pump inhibitors - % 33 29 Drug-eluting stent implanted - % 98 99

Death, MI, stroke, stent thrombosis, urgent revascularization Primary Endpoint up to 18 months Death, MI, stroke, stent thrombosis, urgent revascularization Event Probability N at risks DAPT 635 633 613 593 513 440 SAPT 624 611 591 572 488 411 Follow-up (days) HR = 1.17 [0.68-2.03] p= 0. 5750 DAPT SAPT ----- 3.8% 4.3%

All ischemic Endpoints   DAPT SAPT HR [95%CI] P Primary End Point* 3.8 4.3 1.17 [0.68; 2.03] 0.57 Stent thrombosis or Urgent Revasc 1.3 1.6 1.30 [0.51;3.30] 0.58 Death or myocardial Infarction - % 2.2 2.7 1.26 [0.62 ;2.55] 0.52 Any death - % 1.1 1.4 1.32 [0.49 ;3.55] Myocardial infarction - % 1.04 [0.41 ;2.62] 0.94 Stent thrombosis - % 0.5 Stroke or TIA- % 0.9 0.6 0.69 [0.19;2.44] 0.56 Urgent revascularization - % 1.17 [0.45 ;3.04] 0.74 *Any death, Myocardial infarction, stent thrombosis, stroke or transient ischemic attack, urgent revascularization

Key Safety Outcome Whole population DAPT SAPT 1.1 0.2 0.8 0.3 1.9 0.5   DAPT SAPT HR [95%CI] P Major bleeding - % 1.1 0.2 0.15 [0.02; 1.20] 0.073 Minor bleeding - % 0.8 0.3 0.41 [0.08 ;2.13] 0.29 Major or minor bleeding - % 1.9 0.5 0.26 [0.07 ;0.91] 0.035 BARC III and V 0.15 [0.02 ;1.20] = STEEPLE definitions - Montalescot G, et al. N Engl J Med 2006; 355:1006–17

ARCTIC-INTERRUPTION Half of the patients could not be randomized 1 year after stenting The randomized patients were at lower risk No ischemic benefit of DAPT continuation beyond one year Significant more major or minor bleedings with DAPT continuation Findings consistent across pre-specified subgroups and prior studies