Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias: a systematic review and meta-analysis

Abstract

Background Cardiac arrhythmias are associated with poorer outcomes in patients with heart failure (HF), diabetes mellitus (DM), and chronic kidney disease (CKD). Previous studies have shown inconsistent conclusions regarding the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the risk of developing arrhythmias. This study aims to investigate the association of SGLT2i treatment with arrhythmia outcomes in clinical trials of patients with HF, DM, or CKD. Methods MEDLINE, EMBASE, and ClinicalTrials.gov were searched from inception up to 27 August 2020. Randomized controlled trials that randomized patients with DM, CKD, or HF to SGLT2i or placebo were included. The outcomes of interest include atrial fibrillation (AF), embolic stroke, atrial flutter (AFL), AF/AFL, ventricular tachycardia (VT), and cardiac arrest. Relative risks (RRs) and 95% confidence intervals (CI) were pooled using a random-effects model. Results Out of 4,532 citations, 22 trials with altogether 52,115 patients were included (mean age 63.2 years; 33,747 [64.8%] of participants were men). SGLT2i were associated with a lower risk of AF (RR 0.82, 95% CI 0.70–0.96), embolic stroke (RR 0.32, 95% CI 0.12–0.85), AF/AFL (RR 0.82, 95% CI 0.71–0.95), and VT (RR 0.73, 95% CI 0.53–0.99), while the risk reductions in AFL (RR 0.83, 95% CI 0.58–1.17) and cardiac arrest (RR 0.83, 95% CI 0.61–1.14) did not reach statistical significance. The associations appeared to be consistent across different baseline conditions (DM vs CKD vs HF; atherosclerotic cardiovascular disease [ASCVD] vs no ASCVD) and the SGLT2i used. Conclusions SGLT2i reduced the risk of cardiac arrhythmias. Our study provides further evidence for recommending the use of SGLT2i in patients with DM, CKD, and HF. Further research is needed to fully elucidate the mechanism by which SGLT2i protect against arrhythmias.

Electrical Features of the Diabetic Myocardium. Arrhythmic and Cardiovascular Safety Considerations in Diabetes

“…In newly diagnosed diabetic patients, SGTL2 inhibitors associates with a reduced risk of new onset arrhythmia (Chen et al, 2020). Similarly, recent meta-analysis examining arrhythmia outcomes, like atrial fibrillation and ventricular tachycardia, found that SGLT2 inhibitors treatment reduces the risk of cardiac arrhythmias in diabetic patients (Li et al, 2021). However, in most trials, information regarding preexisting arrhythmia and anti-arrhythmic therapy were not available.…”

Association Between SGLT2is and Cardiovascular and Respiratory Diseases: A Meta-Analysis of Large Trials

“…Three previous meta-analyses ( Li et al, 2021a ; Li et al, 2021b ; Zhou et al, 2021 ) identified SGLT2is with the reduced risk of atrial fibrillation, whereas they failed to explore the association between SGLT2is and bradycardia. Our meta-analysis further revealed the association between use of SGLT2is and a lower risk of bradycardia besides that of atrial fibrillation.…”

Cardioprotection by SGLT2 Inhibitors—Does It All Come Down to Na+?

“…In addition, in a huge cohort study with almost 160,000 diabetic patients the adjusted hazard ratio for new onset of arrhythmia (including supraventricular and ventricular arrhythmias) was 0.83 (CI 0.751–0.916) in the SGLT2i group [ 147 ]. Finally, a recently published meta-analysis including 22 trials with in sum 52,115 patients suggests that SGLT2i reduce the risk of AF, embolic stroke, and ventricular tachycardia (VT) with consistent associations for patients with diabetes mellitus, heart failure, or chronic kidney disease [ 148 ]. Thus, although evidence from prospective trials investigating the effects of SGLT2i on arrhythmic events as a primary outcome is still lacking, one can assume that SGLT2i have anti-arrhythmic properties.…”