IMPORTANCE Antiplatelet monotherapy in the chronic maintenance period for patients with high bleeding risk (HBR) and those who have undergone complex percutaneous coronary intervention (PCI) has not yet been explored.

OBJECTIVE To compare clopidogrel vs aspirin monotherapy in patients with HBR and/or PCI complexity.

DESIGN, SETTING, AND PARTICIPANTS This post hoc analysis of the multicenter HOST-EXAM Extended study, an open-label trial conducted across 37 sites in South Korea, enrolled patients from 2014 to 2018 with up to 5.9 years of follow-up. The analysis was conducted from February to November 2023. Patients who maintained dual antiplatelet therapy (DAPT) event-free for 6 to 18 months following PCI were included.

INTERVENTIONS Patients were randomized to receive either clopidogrel or aspirin in a 1:1 ratio. Those with sufficient data to assess HBR or complex PCI were analyzed.

MAIN OUTCOMES AND MEASURES Coprimary end points were thrombotic composite end point (cardiovascular death, nonfatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and definite/probable stent thrombosis) and any bleeding (Bleeding Academic Research Consortium type 2 to 5).

RESULTS Of 3974 patients included (mean [SD] age, 63.4 [10.7] years; 2976 male [74.9%]), 866 had HBR (21.8%), and 849 underwent complex PCI (21.4%). Clopidogrel as compared with aspirin was associated with lower rates of thrombotic and bleeding events regardless of HBR and/or PCI complexity. For the thrombotic composite end point, the hazard ratio (HR) was 0.75 (95% CI, 0.53-1.04) among HBR vs 0.62 (95% CI, 0.48-0.80) among patients without HBR (P for interaction = 0.38) and 0.49 (95% CI, 0.32-0.77) among patients with complex PCI vs 0.74 (95% CI, 0.59-0.92) among patients with noncomplex PCI (P for interaction = 0.12). The reduction in bleeding by clopidogrel compared with aspirin was consistent among both patients with HBR (HR, 0.82; 95% CI, 0.56-1.21) and patients without HBR (HR, 0.58; 95% CI, 0.40-0.85; P for interaction = 0.20) and among patients undergoing complex PCI (HR, 0.79; 95% CI, 0.47-1.33) vs noncomplex PCI (HR, 0.68; 95% CI, 0.50-0.93; P for interaction = 0.62).

CONCLUSIONS AND RELEVANCE In this study, in patients who experienced PCI and were event-free during 6 to 18 months of DAPT, the beneficial impact of clopidogrel monotherapy over aspirin monotherapy was consistent, regardless of bleeding risk and/or PCI complexity.

TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02044250.