Background: Dual antiplatelet therapy (DAPT) with aspirin as a background therapy has become the standard care following percutaneous coronary intervention (PCI). However, some adverse non-cardiac 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 retain the antithrombotic efficacy, but its combination with a P2Y12 inhibitor is still lack of randomized clinical trial (RCT) evidence.

Methods: In this randomized, open-label, non-inferiority trial, patients with negative cardiac troponin undergoing coronary drug-eluting stent (DES) implantation were randomly assigned in a 1:1 ratio to receive either indobufen-based DAPT (indobufen 100mg twice a day plus clopidogrel 75mg/d for 12 months) or conventional DAPT (aspirin 100mg/d plus clopidogrel 75mg/d for 12 months). The primary endpoint was a 1-year composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), ischemic stroke, definite or probable stent thrombosis (ST), or Bleeding Academic Research Consortium (BARC) criteria type 2, 3 or 5 bleeding. The endpoints were adjudicated by an independent Clinical Event Committee.

Results: 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 endpoint occurred in 101 (4.47%) patients in the indobufen-based DAPT group and 140 (6.11%) patients in the conventional DAPT group (absolute difference -1.63%, pnon-inferiority <0.001; hazard ratio (HR) 0.73, 95% CI 0.56 to 0.94, p=0.015). CV death, nonfatal MI, ischemic stroke and ST were observed in 0.13%, 0.40%, 0.80%, and 0.22% of patients in the indobufen-based DAPT group, and 0.17%, 0.44%, 0.83%, and 0.17% of patients in the conventional DAPT group (all p>0.05). The occurrence of BARC criteria type 2, 3 or 5 bleeding events was lower in the indobufen-based DAPT group compared to the conventional DAPT group (2.97% vs 4.71%, HR 0.63, 95%CI 0.46 to 0.85, p=0.002), with main decrease in type 2 bleeding (1.68% vs 3.49%, HR 0.48, 95%CI 0.33 to 0.70, p<0.001).

Conclusions: In Chinese patients with negative cardiac troponin undergoing DES implantation, indobufen plus clopidogrel DAPT compared with aspirin plus clopidogrel DAPT significantly reduced the risk of 1-year net clinical outcomes, which was mainly driven by a reduction in bleeding events without an increase in ischemic events.