OVER-TIME II Trial: Design and Rationale of a Multicenter Randomized Study Evaluating Antithrombotic Strategies in Patients with Acute Coronary Syndrome and Coronary Artery Ectasia

Abstract Introduction Coronary artery ectasia (CAE) is characterized by diffuse coronary dilatation and increased thrombotic risk. In patients with acute coronary syndrome (ACS) and CAE, the optimal antithrombotic strategy remains unclear. Previously, an exploratory trial suggested that the combination of antiplatelet monotherapy plus oral anticoagulation may reduce ischemic events without increasing bleeding risk compared to dual antiplatelet therapy (DAPT), although it was underpowered for definitive conclusions. Aim To evaluate the efficacy and safety of antiplatelet monotherapy plus direct oral anticoagulation compared with DAPT in patients with ACS and culprit-vessel CAE in a multicenter randomized setting. Methods OVER-TIME II is a multicenter, multinational, randomized, open-label clinical trial with 1:1 allocation comparing acetylsalicylic acid 100 mg plus clopidogrel 75 mg versus clopidogrel 75 mg plus rivaroxaban 15 mg daily. The study will include 326 patients with ACS and culprit-vessel CAE. Patients will be followed for 12 months. The co-primary efficacy endpoint is time to first occurrence of a composite of cardiovascular death, non-fatal myocardial infarction, or repeat revascularization. The co-primary safety endpoint is time to first occurrence of major or minor bleeding defined by the BARC criteria. Secondary endpoints include individual components of the primary outcomes. Exploratory analyses will include genomic and transcriptomic profiling through DNA and RNA sampling to identify molecular signatures associated with thrombotic risk, treatment response, and clinical outcomes. Conclusion OVER-TIME II is designed to provide robust multicenter randomized evidence regarding the efficacy and safety of an anticoagulation-based strategy in patients with ACS and CAE, with the potential to contribute to future clinical research and guideline development.