Less bleeding by omitting aspirin in non-ST-segment elevation acute coronary syndrome patients (LEGACY)
Abstract
Abstract Background Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12-inhibitor, reduces the risk of stent-related and non-stent related ischemic events among patients undergoing percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). DAPT has been recommended for at least 12 months post PCI. However, this is associated with an increased risk of (major) bleeding. Improvements in stent technology and pharmacology have shifted the focus to early aspirin withdrawal strategies. Previous trials have demonstrated that early aspirin withdrawal (i.e., P2Y12-monotherapy) reduces bleeding, while preserving the antithrombotic benefits of DAPT. However these trial included 1 to 3 months of DAPT, before omitting aspirin, whereas the average daily bleeding risk is the highest during this early period post PCI. It is unclear whether immediately omitting aspirin after PCI reduces the rate of bleeding, while remaining non-inferior to 12 months DAPT regarding ischemic events in patient with NSTE-ACS. Methods LEGACY is an open-label, international, multicentre, randomized controlled trial, designed to evaluate the efficacy and safety of immediately omitting aspirin versus DAPT in 3,090 NSTE-ACS patients. Patients will be randomized 1:1 after successful PCI to 12 months P2Y12-inhibitor monotherapy or 12 months DAPT. The primary bleeding endpoint is major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3 or 5 bleeding at 12 months. The primary ischemic endpoint is defined as the composite of all-cause death, myocardial infarction or stroke at 12 months (figure 1). Results Between May 2022 and February 2025, approximately 2300 (75%) patients have been enrolled in 27 centres from The Netherlands, Belgium, Estonia and Poland. Enrolment is expected to be completed by August 2025 and the last follow-up visit is expected to occur in August 2026. Conclusions LEGACY is the first randomized controlled trial to investigate the possibility of immediately omitting aspirin in the 12 months following PCI in a broad spectrum of NSTE-ACS patients. This trial will provide novel insights on clinical outcomes, cost-effectiveness and medication adherence in a completely aspirin-free antiplatelet strategy after PCI for NSTE-ACS.