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
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 ischaemic events without increasing bleeding risk compared to dual antiplatelet therapy (DAPT), although it was underpowered for definitive conclusions.
Aims: 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.
Methods and results: 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.
Conclusion: 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.
Registration: NCT07511257. The trial is registered and publicly available on ClinicalTrials.gov and is currently actively recruiting patients.
Related
- A Randomized Controlled Trial Evaluating a Community-Based, Family Network Heart Health Intervention - the SERVE OC Trial: Design, Rationale and Baseline Findings
- RESULT-Hip. The impact of restrictive compared with liberal transfusion strategy on cardiac injury and death in patients undergoing surgery for hip fracture : protocol for a multicentre, randomized controlled trial of two blood transfusion strategies.
- OviTex versus synthetic graft in robotic prolapse surgery (ProTex): rationale and study protocol of a multicentre, phase II and III, partially randomised patient preference trial
- Causal discovery and treatment effect heterogeneity of futile recanalisation (CADISTH) for large vessel occlusion stroke: protocol and rationale for a multicentre prospective cohort study
- NETs and the thrombo-immune microenvironment: immune heterogeneity in recanalization, reperfusion, hemorrhagic transformation, and antithrombotic strategies
BibTeX
@article{adameaviles2026overtime,
title = {{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}},
author = {Edith Adame-Avilés and Diego Araiza-Garaygordobil and Lissette García-Mena and Marco Alcocer-Gamba and Ana Cristina Maldonado-May and Ricardo Álvarez-Santana and José Raúl Nieto-Saucedo and Alejandro Iván Rojas-Arriaga and Rodrigo Gopar-Nieto and Jorge Daniel Sierra-Lara Martínez and Luis Alfonso Marroquín-Donday and Jesús Díaz-Marín and Leonor Jacobo-Albavera and María Alexandra Arias-Mendoza and Ajit S Mullasari},
journal = {European heart journal open},
year = {2026},
month = sep,
doi = {10.1093/ehjopen/oeag161},
url = {https://europepmc.org/article/PMC/PMC13728344},
note = {CC BY},
}
RIS
TY - JOUR
TI - 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
AU - Edith Adame-Avilés
AU - Diego Araiza-Garaygordobil
AU - Lissette García-Mena
AU - Marco Alcocer-Gamba
AU - Ana Cristina Maldonado-May
AU - Ricardo Álvarez-Santana
AU - José Raúl Nieto-Saucedo
AU - Alejandro Iván Rojas-Arriaga
AU - Rodrigo Gopar-Nieto
AU - Jorge Daniel Sierra-Lara Martínez
AU - Luis Alfonso Marroquín-Donday
AU - Jesús Díaz-Marín
AU - Leonor Jacobo-Albavera
AU - María Alexandra Arias-Mendoza
AU - Ajit S Mullasari
PY - 2026
DA - 2026/09/30
JO - European heart journal open
DO - 10.1093/ehjopen/oeag161
UR - https://europepmc.org/article/PMC/PMC13728344
AB - 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 ischaemic events without increasing bleeding risk compared to dual antiplatelet therapy (DAPT), although it was underpowered for definitive conclusions. Aims: 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. Methods and results: 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. Conclusion: 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. Registration: NCT07511257. The trial is registered and publicly available on ClinicalTrials.gov and is currently actively recruiting patients.
SN - 2752-4191
ER -