Key Points:
- Despite prior data suggesting decrease in metabolic stress may reduce atrial fibrillation (AF) progression, the effects of aggressive lifestyle and risk factor modifications (LRFM) or metformin on AF progression remain unknown.
- In this prospective, randomized, open-label clinical trial, 149 patients with atrial fibrillation and an implanted cardiac device capable of continuous AF monitoring were randomized to standard of care, metformin, LRFM or metformin + LRFM.
- Metformin, LRFM, or the combination did not reduce AF burden compared to standard of care although both LRFM arms reduced AF symptom scores.
Prior data has suggested that atrial fibrillation (AF) susceptibility and progression may be associated with metabolic stress. Metformin, nutrient deprivation, and exercise are reported to have effects on metabolic stress. It is unclear if these aggressive lifestyle modifcations and metformin would reduce progression and burden of atrial fibrillation.
The Metformin and Lifestyle/Risk Factor Modification for Upstream Prevention of Atrial Fibrillation Progression (TRIM-AF) was a prospective, randomized, open-label, blinded endpoint clinical trial. The study randomized participants with atrial fibrillation and an implanted pacemaker (PM) or cardioverter-defibrillator (ICD) in a 2×2 design of standard of care versus metformin versus lifestyle and risk factor modification (LRFM) or both metformin and LRFM.
The results of the trial were presented as a late breaking clinical trial at the American Heart Association on November 18, 2024. Among the 149 eligible participants who underwent randomization, the average age was 74 years, 39% were women, and median baseline AF burden was 4.3%. At study enrollment, 118 (79.2%) participants had a diagnosis of hypertension; 13 (8.7%) had a diagnosis of Type 2 diabetes; 57 (38.3%) had a diagnosis of coronary artery disease; 102 (68.5%) had a pacemaker; and 47 (31.5%) had an implantable cardioverter defibrillator. There were no significant differences in the baseline characteristics between the groups, except there were more patients with hypertension in the two groups not receiving metformin compared to the two groups that received metformin (86.5% and 72%, respectively).
At 9-12 months, there was no difference in AF burden between any of the groups with the standard of care group also experiencing a 74% reduction in AF burden. AF symptom scores improved in the two LRFM arm.
Limitations of the trial include small size, high number (up to one-third) of participants in the metformin arms who had to discontinue the medication due to gastrointenstinal side effects, and the COVID-19 pandemic beginning in the middle of the study thus limiting enrollment and in-person visits.
Dr. Mina Chung, the lead author on the study concluded that “at this time, metformin alone should not be recommended as an upstream therapy for atrial fibrillation. The combination of metformin and lifestyle/risk factor modification appeared to show some benefits, but these only reached levels similar to the standard of care arm.”