Keerthenan Raveendra

Aims: Electronic health records (EHRs) can be used to target atrial fibrillation (AF) screening. We evaluated the performance of risk prediction models scalable across nationwide EHRs. Methods and results: This retrospective cohort study included individuals aged ≥30 years without diagnosed AF in the Clalit Health Services (Israel) EHR dataset between 1 January 2019 and 30 June 2019. The primary outcome was a diagnosis of AF or atrial flutter within 6 months. The FIND-AF, CHA2DS2-VASc, and C2HEST scores were evaluated, with prediction performance assessed overall and by sex. The optimum threshold to apply in prospective screening was determined with a lift analysis. Of 2 166 795 individuals in the cohort, 4275 developed AF within 6 months. Prediction performance was strongest for FIND-AF [area under the receiver operating characteristic curve (AUROC) 0.871, 95% confidence interval (CI) 0.864–0.877; calibration slope 0.73, 95% CI 0.67–0.79] compared with CHA2DS2-VASc (AUROC 0.838, 95% CI 0.831–0.845; calibration slope 0.63, 95% CI 0.60–0.67) and C2HEST scores (AUROC 0.834, 95% CI 0.823–0.844; calibration slope 0.62, 95% CI 0.58–0.65), including in women (FIND-AF AUROC 0.883, 95% CI 0.876–0.889; CHA2DS2-VASc AUROC 0.865, 95% CI 0.858–0.872; C2HEST AUROC 0.853, 95% CI 0.846–0.861) and men (FIND-AF AUROC 0.857, 95% CI 0.850–0.864; CHA2DS2-VASc AUROC 0.835, 95% CI 0.828–0.843; C2HEST AUROC 0.814, 95% CI, 0.806–0.822). Lift analysis suggested that screening the top 15% of FIND-AF risk compared with screening by age would identify 72% compared with 63% of AF diagnoses. Conclusion: The FIND-AF machine learning algorithm was scalable in routine EHR data with good discrimination for incident AF. Prospective evaluation is now required to evaluate risk-guided AF screening.

Introduction: Heart failure (HF) is a common sequela of diabetes and obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists may prevent HF events. This meta-analysis estimates absolute risk reduction (ARR) and number needed to treat (NNT) for GLP-1 receptor agonists to prevent one HF event in patients with type 2 diabetes and/or obesity, including those without baseline HF. Methods: The Medline, Embase, and Cochrane Central databases were searched to 04 April 2025 for placebo-controlled randomized controlled trials (RCTs) of GLP-1 receptor agonists in a type 2 diabetes and/or obesity indication with a prespecified HF event endpoint. Random effects meta-analysis using the Mantel-Haenszel Method was performed to synthesize risk ratios (RR), ARRs, and NNTs with 95% confidence intervals (CI). Results: Twelve placebo-controlled RCTs involving 95 023 patients were included. GLP-1 receptor agonists reduced HF events by 12% (RR 0.88, 95% CI 0.82–0.95; ARR 0.42%, 95% CI 0.17%–0.62%; NNT 238, 95% CI 161–588), and, in those without baseline HF, by 19% (RR 0.81, 95% CI 0.72–0.90; ARR 0.60%, 95% CI 0.32%-0.89%; NNT 167, 95% CI 113–313). Semaglutide reduced the risk of HF events by 16% (RR 0.84, 95% CI 0.74–0.95; ARR 0.62%, 95% CI 0.19%-1.00%; NNT 161, 95% CI 100–526), and by 31% in those without baseline HF (RR 0.69, 95% CI 0.55–0.88; ARR 1.25%, 95% CI 0.48%-1.82%; NNT 80, 95% CI 55–208). Conclusion: GLP-1 receptor agonists have limited absolute benefit for preventing HF events in patients with type 2 diabetes and/or obesity, including in those without baseline HF. Systematic review registration: PROSPERO: CRD420251074882

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 glucagon-like peptide-1 receptor agonists (RR 0.79, 95% CI 0.63–0.99). However, the number of AF events per trial was low and none were adequately powered for incident AF. Conclusions: 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.