Key result
SGLT2 inhibitors cut AF risk ~14% vs. placebo, with protection confirmed in HFrEF.
Why the study?
Do SGLT2 inhibitors prevent atrial fibrillation in patients with cardiovascular disorders including heart failure?
Meta-Analysis (n=112,031)
Do SGLT2 inhibitors prevent atrial fibrillation in patients with cardiovascular disorders including heart failure?
Relative Risk: 0.86 (95% CI 0.77–0.96)
SGLT2 inhibitors reduce the risk of developing atrial fibrillation, particularly in patients with HFrEF, though this benefit is attenuated in patients with higher ejection fractions or hypertension.
Supports SGLT2 inhibitor use for AF prevention in HFrEF; confirms benefit in reduced EF but leaves open questions in preserved EF.
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.
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Fedele et al. (2025) conducted a meta-analysis in cardiovascular disorders (n=112,031). SGLT2 inhibitors vs. placebo was evaluated on development of atrial fibrillation (RR 0.86, 95% CI 0.77-0.96). SGLT2 inhibitors prevented atrial fibrillation compared to placebo (RR 0.86; 95% CI 0.77-0.96), with the protective effect confirmed in HFrEF but not in HFmrEF/HFpEF.
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