Sodium-Glucose Co-Transporter Inhibitors and Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background Sodium-glucose co-transporter (SGLT) inhibitors reduce cardiovascular outcomes including mortality in several populations; however, their effect on atrial fibrillation/flutter (AF) remains unclear. Our objective was to determine whether SGLT inhibitors reduce AF and whether a history of AF modifies the effect of SGLT inhibitors on the composite of heart failure hospitalization or cardiovascular death. Methods and Results We searched MEDLINE, Embase, and CENTRAL to March 2021. Pairs of reviewers identified randomized controlled trials that compared an SGLT inhibitor with placebo or no therapy. We pooled data using RevMan 5.4.1, assessed risk of bias using the Cochrane tool, and determined the overall quality of evidence using Grades of Recommendation, Assessment, Development and Evaluation. Thirty-one eligible trials reported on AF events (75 279 participants, mean age 62 years, 35.0% women). Moderate quality evidence supported a lower risk of serious AF events with SGLT inhibitors (1.1% versus 1.5%; risk ratio 0.75 [95% CI, 0.66-0.86]; I²=0%). A similar reduction in total AF events was also noted with SGLT inhibitors. Three trials reported on heart failure hospitalization/cardiovascular death stratified by a baseline history of AF (18 832 participants, mean age 66 years, 38.1% women); in patients with a history of AF, SGLT inhibitors resulted in a lower risk in the composite of heart failure hospitalization or cardiovascular death (hazard ratio, 0.70 [95% CI, 0.57-0.85]; I²=0%)-similar to the effect estimate for patients without AF, P value for interaction: 1.00. Conclusions SGLT inhibitors may reduce AF events and likely reduce heart failure hospitalization/cardiovascular death to a similar extent in patients with and without AF.

Keywords: SGLT inhibitors; atrial fibrillation; atrial flutter; gliflozins.

Figure 1. Forest plot comparing serious atrial fibrillation or atrial flutter events between patients on SGLT inhibitors vs placebo/control in randomized controlled trials.

Square markers represent point estimates of RR for individual studies, with square size representing proportional weight given to each study in the meta‐analysis. Horizontal lines indicate 95% CIs. The solid diamond represents the estimated 95% CI for effect size of all meta‐analyzed data. M‐H, Mantel‐Haenszel; RR, relative risk; and SGLT, sodium‐glucose co‐transporter.

Figure 2. Forest plot demonstrating composite of heart failure hospitalization/urgent visit or cardiovascular death between patients on SGLT inhibitors vs placebo/control in randomized controlled trials stratified by presence or absence of atrial fibrillation/flutter at baseline.

Square markers represent point estimate of HR for individual studies, with square size representing proportional weight given to each study in the meta‐analysis. Horizontal lines indicate 95% CIs. The solid diamonds represent the estimated 95% CI for effect size of all meta‐analyzed data. AF indicates atrial fibrillation; AFl, atrial flutter; EMPA‐REG OUTCOME, Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes; HR, hazard ratio; SGLT, sodium‐glucose co‐transporter; SOLOIST, Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure; and SCORED, Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease.