SODIUM-GLUCOSE CO-TRANSPORTER INHIBITORS AND ATRIAL FIBRILLATION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

BACKGROUND Sodium-glucose co-transporter (SGLT) inhibitors reduce heart failure (HF) hospitalization and cardiovascular death in several populations, including patients with type 2 diabetes mellitus, renal impairment, HF and cardiovascular disease. The efficacy of SGLT inhibitors in patients with atrial fibrillation/flutter (AF) and their effect on incidence or recurrence of AF has yet to be systematically assessed. Our objectives were to determine whether sodium-glucose co-transporter (SGLT) inhibitors reduce atrial fibrillation/flutter (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 to placebo or no therapy. The primary outcome was the rate of AF reported as an adverse event. The secondary outcome was a composite of hospitalization/urgent visit for HF or cardiovascular death, stratified by history of AF at baseline. We assessed risk of bias using the Cochrane tool and the overall quality of evidence using GRADE. Thirty eligible trials reported on AF events (71,553 participants, mean age 62 years, 35.6% women). Moderate quality evidence supported a lower risk of AF events with SGLT inhibitors (1.0% versus 1.4%; risk ratio 0.78; 95% confidence interval [CI] 0.68-0.89; I2=0%). Three trials reported on the secondary composite outcome (18,826 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 HF hospitalization or cardiovascular death (hazard ratio [HR] 0.70; 95% CI 0.57-0.85; I2=0%) – similar to the effect estimate for patients without AF (HR 0.70; 95% CI 0.61-0.79; I2=0%), p-value for interaction: 1.00. CONCLUSION SGLT inhibitors may reduce the incidence or recurrence of AF. These drugs reduce a composite of HF hospitalization or cardiovascular death, both in patients with and without AF.