OVER-TIME II trial: design and rationale of a multicentre randomized study evaluating antithrombotic strategies in patients with acute coronary syndrome and coronary artery ectasia

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 ischaemic events without increasing bleeding risk compared to dual antiplatelet therapy (DAPT), although it was underpowered for definitive conclusions.

The aim of this study is 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 multicentre randomized setting.

OVER-TIME II is a multicentre, multinational, randomized, open-label clinical trial with 1:1 allocation comparing acetylsalicylic acid 100 mg plus clopidogrel 75 mg vs. 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 the time to first occurrence of a composite of cardiovascular death, non-fatal myocardial infarction, or repeat revascularization. The co-primary safety endpoint is the time to first occurrence of major or minor bleeding defined by the Bleeding Academic Research Consortium 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.

OVER-TIME II is designed to provide robust multicentre 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.

NCT07511257. The trial is registered and publicly available on ClinicalTrials.gov and is currently actively recruiting patients.