Potential Additional Benefits of Cardio-renal-metabolic Therapies on the Incidence of Atrial Fibrillation

Drug therapy for cardio-renal-metabolic diseases can prevent

new-onset atrial fibrillation. A meta-analysis investigated

which pharmacotherapies have an effect on the risk of new-­

onset atrial fibrillation.

To this end, 249 randomized clinical trials (RCTs) involv-

ing 745,041 patients were analyzed, which compared the

effect of a non-antiarrhythmic cardio-renal-metabolic drug

to a control group or another active substance in terms of

the occurrence of atrial fibrillation.

A total of 249 RCTs involving 745,041 patients were in-

cluded, of which 207 identified atrial fibrillation based on

reports of adverse events, 161 were placebo-controlled,

and 15 had atrial fibrillation as a prespecified endpoint. In

the placebo-controlled trials there were significant differ-

ences in the incidence of atrial fibrillation in the treatment

of heart failure with reduced ejection fraction (HFrEF) with

angiotensin-converting enzyme (ACE) inhibitors and angio-

tensin receptor blockers (ARBs) (relative risk [RR]: 0.69;

95% confidence interval [CI]: 0.60–0.80), mineralocorticoid

receptor antagonists (MRA) (RR: 0.62; 95% CI: 0.43–0.90),

and SGLT2 inhibitors (RR: 0.62; 95% CI: 0.44–0.87), as well

as in the treatment of chronic kidney disease with SGLT2

inhibitors (RR: 0.53; 95% CI: 0.33–0.85) and in the treat-

ment of obesity with GLP-1 receptor agonists (GLP-1 RA)

(RR: 0.79; 95% CI: 0.63–0.99). However, the number of

atrial fibrillation events per study was low, and none of the

studies was sufficiently conclusive with regard to the occur-

rence of atrial fibrillation.

This meta-analysis is limited by the fact that it is predom-

inantly based on post hoc data, which often originates from

reports of adverse events and is subject to bias as well as

over- and underestimation with regard to treatment effects.

However, according to the study authors, the available data

provides hypothesis-generating estimates for future stud-

ies that the treatment of HFrEF with ACE inhibitors/ARBs,

MRA, and SGLT2 inhibitors, the treatment of chronic kidney

disease with SGLT2 inhibitors, and the treatment of obesity

with GLP-1 RA could be associated with a relative risk re-

duction for the occurrence of atrial fibrillation. 

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Source: Raveendra K et al.: Non-antiarrhythmic pharmacotherapy in cardio-renal-metabolic disease and incident atrial fibrillation: a trial meta-analysis. Eur Heart J. 2026 Jan 28:ehag021. doi:10.1093/eurheartj/ehag021

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