Aspirin versus Clopidogrel monotherapy beyond 1 month after complex percutaneous coronary intervention: A pre-specified subgroup analysis of the STOPDAPT-3 trial.

Aims: There were no previous studies comparing aspirin versus P2Y12 inhibitor monotherapy following short dual antiplatelet therapy (DAPT) after complex percutaneous coronary intervention (PCI).
Methods and Results: We conducted a prespecified subgroup analysis based on complex PCI in the 1-year results of the STOPDAPT-3 trial, which randomly compared 1-month DAPT followed by aspirin monotherapy (aspirin group) to 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). The main analysis in the present study was the 30-day landmark analysis. The co-primary endpoints were cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) and major bleeding (Bleeding Academic Research Consortium 3 or 5). In the 30-day landmark analysis (N = 5833), there were 1415 patients (24.3%) who underwent complex PCI. There was a significant interaction between complex PCI and the effect of aspirin group relative to clopidogrel group for cardiovascular events (complex PCI: 3.3% versus 5.2%, non-complex PCI, 4.3% versus 3.6%, interaction P = 0.04) and net adverse clinical events (complex PCI: 4.8% versus 7.2%, non-complex PCI: 5.3% versus 4.4%, interaction P = 0.02), but not for bleeding events (complex PCI: 2.1% versus 2.7%, non-complex PCI: 1.7% versus 1.4%, interaction P = 0.35).
Conclusions: There was a significant interaction between complex PCI and the effect of aspirin monotherapy relative to clopidogrel monotherapy beyond 1 month and up to 1 year for cardiovascular events due to numerically lower risk of aspirin monotherapy in patients with complex PCI, while the effect of aspirin monotherapy relative to clopidogrel monotherapy was not different for bleeding regardless of complex PCI. Clinical trial registration: ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111.
(© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.)