Potent P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: Rationale and design of the STARS DAPT randomized pilot trial

ABSTRACT Background Dual antiplatelet therapy (DAPT) for 12 months is the current standard of care for patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Recent evidence indicates that potent oral P2Y 12 inhibitor-based single antiplatelet therapy (SAPT) after 1 to 3 months of DAPT following drug-eluting-stent (DES) implantation reduces major bleeding events without increasing the risk of major ischemic outcomes in patients with acute coronary syndrome. However, the optimal timing of aspirin discontinuation in STEMI patients treated with P2Y 12 inhibitor-based SAPT remains uncertain. Design STARS DAPT is an investigator-initiated, prospective, multicenter, open-label, precision-based, randomized controlled pilot trial with a blinded outcome assessment. Patients with STEMI who underwent successful primary PCI of the culprit lesion with a newer-generation polymer-free DES will be randomized in a 1:1 ratio to potent P2Y 12 inhibitor-based SAPT (with aspirin discontinued after an initial period of DAPT during the index hospitalization and before hospital discharge) for 12 months vs. standard DAPT for 12 months. The primary efficacy endpoint is the rate of major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of all-cause death, non-fatal myocardial re-infarction, non-fatal stroke, urgent target vessel revascularization, or definite/probable stent thrombosis, at 12 months. The primary safety endpoint is Bleeding Academic Research Consortium (BARC) class 3 or 5 major bleeding at 12 months. The study is designed to provide estimates of treatment effects and their precision to inform the design of a subsequent larger randomized trial. Enrolment status The trial aims to recruit a total of 350 patients. The first patient was enrolled on December 1, 2025. Conclusion STARS DAPT is a randomized pilot study assessing the safety and efficacy of a potent oral P2Y 12 inhibitor-based SAPT strategy, with aspirin discontinued after an initial period of DAPT during the index hospitalization and before hospital discharge, following primary PCI with a newer-generation polymer-free DES in patients with STEMI. The findings will inform future large-scale trial design and may help optimize antiplatelet strategies and guide clinical decision-making after primary PCI. Trial Registration Clinicaltrials.gov: Identifier, NCT05785897. Funding source Unrestricted research grant from Concept Medical (Tampa, FL, USA) to Geneva University Hospitals, Switzerland.