{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:33:34Z","timestamp":1791495214302,"version":"4.3.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"23","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2013Haenszel method, with between-study variance estimated using the DerSimonian\u2013Laird method, was performed to synthesize risk ratios (RR) with 95% confidence intervals (CI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u20130.80), mineralocorticoid receptor antagonists (RR 0.62, 95% CI 0.43\u20130.90), and sodium-glucose co-transporter 2 (SGLT2) inhibitors (RR 0.62, 95% CI 0.44\u20130.87); treatment of chronic kidney disease with SGLT2 inhibitors (RR 0.53, 95% CI 0.33\u20130.85); and treatment of obesity with glucagon-like peptide-1 receptor agonists (RR 0.79, 95% CI 0.63\u20130.99). However, the number of AF events per trial was low and none were adequately powered for incident AF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Prospective RCTs with AF as a pre-specified outcome should be integrated into the design of future trials of cardio-renal-metabolic medications to determine whether they reduce incident AF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehag021","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:54:00Z","timestamp":1767963240000},"page":"2922-2933","source":"Crossref","is-referenced-by-count":4,"title":["Non-antiarrhythmic pharmacotherapy in cardio-renal-metabolic disease and incident atrial fibrillation: a trial 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