Prevention of atrial fibrillation with SGLT2 inhibitors across the spectrum of cardiovascular disorders: a meta-analysis of randomised controlled trials

Abstract Background The capability of sodium-glucose cotransporter-2 (SGLT2) inhibitors in preventing atrial fibrillation (AF) has been evaluated in various studies with conflicting results. Recent meta-analyses, including also recent randomised controlled trials (RCTs) focusing on patients with heart failure with preserved ejection fraction (HFpEF), found no preventive effect of SGLT2 inhibitors on AF. Purpose This study aimed to determine whether SGLT2 inhibitors have a protective effect against AF, specifically depending on the baseline clinical condition in which the RCTs were performed. Methods A meta-analysis was performed including RCTs comparing SGLT2 inhibitors with placebo and reporting the number of patients who developed AF in each arm. Risk ratios (RR) for the development of AF with 95% confidence intervals (95% CI) were pooled using a random-effects model. Subgroup analyses were performed classifying RCTs according to the inclusion criteria of each trial (diabetes, chronic kidney disease, heart failure with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and HFpEF). Meta-regressions were performed considering baseline characteristics of RCTs participants. Results 52 RCTs were included. Overall, SGLT2 inhibitors prevented the occurrence of AF (RR = 0.86, 95% CI 0.77-0.96). In the subgroup analysis, the AF-preventive ability of SGLT2 inhibitors was influenced by HF, being preserved in HFrEF, but not in HFmrEF/HFpEF (p-value for group difference = 0.01). Meta-regression showed a reduced efficacy of SGLT2 inhibitors in preventing AF when more patients with hypertension and with higher EF were enrolled (p-value 0.01 for both). Conclusion SGLT2 inhibitors prevent AF. Their protective effect was confirmed in patients without HF or with HFrEF, but not in HFmrEF or HFpEF.Forest plots Systemic effects of SGLT2 inhibitors