Clopidogrel versus Aspirin Monotherapy Beyond 1 Year After PCI: STOPDAPT-2 5-Year Results

It remains unclear whether clopidogrel is better suited than aspirin as the long-term antiplatelet monotherapy following dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). We compared clopidogrel monotherapy following 1-month DAPT (clopidogrel group) with aspirin monotherapy following 12-month DAPT (aspirin group) after PCI for 5 years. STOPDAPT-2 is a multicenter, open-label, adjudicator-blinded, randomized clinical trial conducted in Japan. Patients who underwent PCI with cobalt-chromium everolimus-eluting stents were randomized in a 1-to-1 fashion either to clopidogrel or aspirin groups. The primary endpoint was a composite of cardiovascular outcomes (cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis) or major bleeding (TIMI major or minor bleeding). Among 3005 study patients (Age: 68.6±10.7 years; Women: 22.3%; Acute coronary syndrome: 38.3%), 2934 patients (97.6%) completed 5-year follow-up (adherence to the study drugs at 395 days: 84.7% and 75.9%). Clopidogrel group compared with aspirin group was noninferior, but not superior for the primary endpoint (11.75% and 13.57%; HR 0.85 [95%CI: 0.70-1.05], Pnoninferiority<0.001, Psuperiority=0.13), while it was superior for the cardiovascular outcomes (8.61% and 11.05%, HR 0.77 [95%CI: 0.61-0.97], P=0.03), and not superior for major bleeding (4.44% and 4.92%; HR 0.89 [95%CI: 0.64-1.25], P=0.51). By the 1-year landmark analysis, clopidogrel was numerically, but not significantly, superior to aspirin for cardiovascular events (6.79% and 8.68%; HR 0.77 [95%CI: 0.59-1.01], P=0.06) without difference in major bleeding (3.99% and 3.32%; HR 1.23 [95%CI: 0.84-1.81], P=0.31). Clopidogrel might be an attractive alternative to aspirin with a borderline ischemic benefit beyond 1-year after PCI.