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Non-antiarrhythmic pharmacotherapy in cardio-renal-metabolic disease and incident atrial fibrillation: a trial meta-analysis

Raveendra K, Nadarajah R, Larvin H, Farooq M, Haris M, Cutting U, Kang J, Wilkinson C et al.

European heart journal, 2026

745 participants

Abstract

Background and aims: Atrial fibrillation (AF) disease burden is increasing. Pharmacotherapy of cardio-renal-metabolic diseases may prevent incident AF. This meta-analysis estimates the effect of different pharmacotherapies on risk of incident AF across cardio-renal-metabolic diseases.

Methods: The Medline, Embase, and Cochrane Central databases were searched to 7 October 2025 for randomized clinical trials (RCTs) comparing the effect of a non-antiarrhythmic cardio-renal-metabolic medication with control or another agent for incident AF. Random-effects meta-analysis using the Mantel-Haenszel method, with between-study variance estimated using the DerSimonian-Laird method, was performed to synthesize risk ratios (RR) with 95% confidence intervals (CI).

Results: Two hundred and forty-nine RCTs involving 745 041 patients were included, of which 207 identified AF through adverse event reports, 161 were placebo-controlled, and 15 had AF as a pre-specified endpoint. In placebo-controlled trials, significant differences in incident AF were observed with treatment of heart failure with reduced ejection fraction with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (RR 0.69, 95% CI 0.60-0.80), mineralocorticoid receptor antagonists (RR 0.62, 95% CI 0.43-0.90), and sodium-glucose co-transporter 2 (SGLT2) inhibitors (RR 0.62, 95% CI 0.44-0.87); treatment of chronic kidney disease with SGLT2 inhibitors (RR 0.53, 95% CI 0.33-0.85); and treatment of obesity with…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 745 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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