MetCool ACS: study protocol for a multicentre quasi-randomised trial of metformin in patients without diabetes after acute coronary syndrome in Poland

INTRODUCTION: Despite advances in coronary intervention and secondary prevention, patients without diabetes who experience acute coronary syndrome (ACS) remain at elevated cardiovascular risk. Metformin has pleiotropic cardiovascular effects beyond glucose lowering, but its role after ACS in people without diabetes is uncertain. METHODS AND ANALYSIS: MetCool ACS is a multicentre, prospective, quasi-randomised, open-label trial enrolling 1000 adults without diabetes hospitalised for ACS and treated with successful percutaneous coronary intervention (PCI) with drug-eluting stent implantation. Allocation is determined by the second digit of the Polish national identification number: even digits allocate to metformin and odd digits to standard care (allocation 1:1). Participants allocated to metformin will receive dose-escalated therapy to 850 mg three times a day (2550 mg/day) for 24 months, followed by 6 months of post-treatment follow-up (total 30 months). The primary endpoint is unplanned coronary revascularisation (PCI or coronary artery bypass grafting) within 30 months after the index ACS-related revascularisation. Secondary endpoints include cardiac death, all-cause death, non-fatal myocardial infarction, non-fatal stroke and safety outcomes. Time-to-event outcomes will be analysed using appropriate survival analysis methods, including Kaplan-Meier estimates, log-rank testing and Cox proportional hazards models, with competing-risk methods applied where appropriate. Detailed statistical methods will be prespecified in the statistical analysis plan. Protocol version: 3.1/2023 (10 January 2023). ETHICS AND DISSEMINATION: The study was approved by the Bioethics Committee at the Military Institute of Medicine (Resolution 55/WIM/2020; 18 November 2020) and the Bioethics Committee at the Military Chamber of Physicians (Resolution 31/23; 27 October 2023). All participants provide written informed consent. Results will be disseminated primarily through peer-reviewed publication and scientific meetings. The trial is covered by clinical trial insurance, including coverage for potential claims arising from harm related to participation in the trial. Any compensation for trial-related harm will be provided in accordance with applicable regulations and the terms and conditions of the insurance policy. TRIAL REGISTRATION NUMBERS: EudraCT 2020-004962-21; EU CT 2024-516589-13-00; NCT05305898.