Indobufen or Aspirin on Top of Clopidogrel After Coronary Drug-Eluting Stent Implantation (OPTION): A Randomized, Open-Label, End Point–Blinded, Noninferiority Trial

Dual antiplatelet therapy (DAPT) with aspirin as a background therapy has become the standard care after percutaneous coronary intervention. However, some adverse noncardiac effects limited the use of aspirin in clinical practice. Thus, evaluation of pharmacological alternatives to aspirin is attractive. Previous data indicated that indobufen could lessen the unwanted side effects of aspirin while retaining the antithrombotic efficacy, but its combination with a P2Y inhibitor still lacks randomized clinical trial evidence. In this randomized, open-label, noninferiority trial, patients with negative cardiac troponin undergoing coronary drug-eluting stent implantation were randomly assigned in a 1:1 ratio to receive either indobufen-based DAPT (indobufen 100 mg twice a day plus clopidogrel 75 mg/d for 12 months) or conventional DAPT (aspirin 100 mg/d plus clopidogrel 75 mg/d for 12 months). The primary end point was a 1-year composite of cardiovascular death, nonfatal myocardial infarction, ischemic stroke, definite or probable stent thrombosis, or Bleeding Academic Research Consortium criteria type 2, 3, or 5 bleeding. The end points were adjudicated by an independent Clinical Event Committee. Between January 11, 2018, and October 12, 2020, 4551 patients were randomized in 103 cardiovascular centers: 2258 patients to the indobufen-based DAPT group and 2293 to the conventional DAPT group. The primary end point occurred in 101 patients (4.47%) in the indobufen-based DAPT group and 140 patients (6.11%) in the conventional DAPT group (absolute difference, -1.63%; 0.05). The occurrence of Bleeding Academic Research Consortium criteria type 2, 3, or 5 bleeding events was lower in the indobufen-based DAPT group compared with the conventional DAPT group (2.97% versus 4.71%; hazard ratio, 0.63 [95% CI, 0.46-0.85]; =0.002), with the main decrease in type 2 bleeding (1.68% versus 3.49%; hazard ratio, 0.48 [95% CI, 0.33-0.70];