METFORMIN FOR ATRIAL FIBRILLATION

Summary

The aim of this multicenter, pragmatic, open-label, randomized, placebo-controlled clinical trial is to test whether repurposing metformin for the treatment of atrial fibrillation will be effective in decreasing patients' hospitalization, adverse major cardiovascular events, and non-cancer death. Participants will be randomized into 2 study arms (385 participant each), whereby: * The Metformin Group (MG): will receive metformin oral tablets in addition to the standard rate/rhythm control strategy and anticoagulation. * The Placebo Control Group (PCG): will receive placebo oral tablets as a control group in addition to the standard rate/rhythm control strategy and anticoagulation. Then both arms will be compared according to the these endpoints: * The primary endpoint is hospitalization due to an episodic AF or an AF with a rapid or slow ventricular response (in the case of permanent AF). * The secondary endpoint is a composite of non-fatal major cardiovascular adverse events or non-cancer death. The non-fatal major cardiovascular adverse events include: * Hospitalization due to heart failure. * Non-fatal myocardial infarction. * Non-fatal stroke. * Hospitalization due to unstable angina.

Timeline

Start

2024-06-01

Primary completion

2025-01

Completion

2025-04

Publications

• Background Chung MK, Eckhardt LL, Chen LY, Ahmed HM, Gopinathannair R, Joglar JA, Noseworthy PA, Pack QR, Sanders P, Trulock KM; American Heart Association Electrocardiography and Arrhythmias Committee and Exercise, Cardiac Rehabilitation, and Secondary Prevention Committee of the Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Council on Lifestyle and Cardiometabolic Health. Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation: A Scientific Statement From the American Heart Association. Circulation. 2020 Apr 21;141(16):e750-e772. doi: 10.1161/CIR.0000000000000748. Epub 2020 Mar 9.
• Background Schwaerzer G. Repurposing metformin for treatment of atrial fibrillation. Nat Cardiovasc Res. 2022 Nov;1(11):972. doi: 10.1038/s44161-022-00170-1. No abstract available.
• Background Lal JC, Mao C, Zhou Y, Gore-Panter SR, Rennison JH, Lovano BS, Castel L, Shin J, Gillinov AM, Smith JD, Barnard J, Van Wagoner DR, Luo Y, Cheng F, Chung MK. Transcriptomics-based network medicine approach identifies metformin as a repurposable drug for atrial fibrillation. Cell Rep Med. 2022 Oct 18;3(10):100749. doi: 10.1016/j.xcrm.2022.100749. Epub 2022 Oct 11.
• Background Vinciguerra M, Olier I, Ortega-Martorell S, Lip GYH. New use for an old drug: Metformin and atrial fibrillation. Cell Rep Med. 2022 Dec 20;3(12):100875. doi: 10.1016/j.xcrm.2022.100875.
• Background Donertas HM, Fuentealba Valenzuela M, Partridge L, Thornton JM. Gene expression-based drug repurposing to target aging. Aging Cell. 2018 Oct;17(5):e12819. doi: 10.1111/acel.12819. Epub 2018 Aug 9.
• Background Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a Tool to Target Aging. Cell Metab. 2016 Jun 14;23(6):1060-1065. doi: 10.1016/j.cmet.2016.05.011.
• Background Ostropolets A, Elias PA, Reyes MV, Wan EY, Pajvani UB, Hripcsak G, Morrow JP. Metformin Is Associated With a Lower Risk of Atrial Fibrillation and Ventricular Arrhythmias Compared With Sulfonylureas: An Observational Study. Circ Arrhythm Electrophysiol. 2021 Mar;14(3):e009115. doi: 10.1161/CIRCEP.120.009115. Epub 2021 Feb 7.
• Background Nantsupawat T, Wongcharoen W, Chattipakorn SC, Chattipakorn N. Effects of metformin on atrial and ventricular arrhythmias: evidence from cell to patient. Cardiovasc Diabetol. 2020 Nov 24;19(1):198. doi: 10.1186/s12933-020-01176-4.

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Indications