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]; I 2 =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]; I 2 =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.

Using real-world data for supporting regulatory decision making: Comparison of cardiovascular and safety outcomes of an empagliflozin randomized clinical trial versus real-world data

“…Several meta-analyses including all trials do show reductions in hemorrhagic stroke ( Tsai et al, 2021 ) and in total stroke ( Mascolo et al, 2021 ), which supports our results. Also, SGLT-2 inhibitors seem to reduce atrial fibrillation ( Pandey et al, 2021 ), which can also explain the stroke protection. It seems reason for the discrepancy is not clear.…”

Elevated premature ventricular complex counts on 24-hour electrocardiogram predict incident atrial fibrillation and heart failure—A prospective population-based cohort study

“…Future studies that address potential drug therapies that have the potential to reduce AF and HF risk in patients with elevated PAC and PVC counts would be of interest, for example sodium-glucose cotransporter-2 inhibitors as a preferred treatment for diabetic patients with PVCs. 23 …”

SGLT2 Inhibitors and Their Antiarrhythmic Properties

“…Another meta-analysis including all clinical trials that investigated SGLT2 inhibitors until December 2020 also reports a significant reduction of the incidence of atrial arrhythmias with an overall prevalence of approximately 1% of the study population [73]. A pooled analysis of 31 randomized clinical trials including more than 75,000 patients found that SGLT2 inhibitor use is associated with a lower incidence and recurrence of atrial fibrillation as well as with a reduced rate of cardiovascular outcomes [95]. Conversely, these findings could not be retraced in another meta-analysis dealing with a similar yet older database based on reported trial data until October 2019 [96].…”