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

Aims The ability of sodium-glucose co-transporter 2 (SGLT2) inhibitors to prevent atrial fibrillation (AF) has been evaluated in various studies with conflicting results. This study aimed to determine whether SGLT2 inhibitors have a protective effect against AF depending on the baseline clinical condition in which the randomized controlled trials (RCTs) were conducted. Methods and results A trial-level meta-analysis was performed including 52 RCTs (112 031 patients) comparing SGLT2 inhibitors with placebo and reporting the number of patients who developed AF in each arm. Risk ratios (RRs) for AF development with 95% confidence intervals (95% CIs) were pooled using a random-effects model. Subgroup analyses were performed by classifying RCTs according to the inclusion criteria of each trial [diabetes, chronic kidney disease, heart failure with reduced ejection fraction (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF)]. Overall, SGLT2 inhibitors prevented 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 RCTs recruiting 9141 patients with HFrEF, but not in those recruiting 12 877 subjects with 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 or higher EF were enrolled (P < 0.01 for both). Conclusion Sodium-glucose co-transporter 2 inhibitors prevent AF. Their protective effect was confirmed in the HFrEF subgroup, but not in RCTs recruiting patients with HFmrEF/HFpEF, possibly indicating a different pathophysiology leading to AF among these conditions. However, given the limitations of a trial-level analysis, these findings are exploratory, pending confirmation from patient-level data.