Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias: a systematic review and meta-analysis.
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.
['Li|Hang-Long|HL|', 'Lip|Gregory Y H|GYH|', 'Feng|Qi|Q|', 'Fei|Yue|Y|', 'Tse|Yi-Kei|YK|', 'Wu|Mei-Zhen|MZ|', 'Ren|Qing-Wen|QW|', 'Tse|Hung-Fat|HF|', 'Cheung|Bernard-M Y|BY|', 'Yiu|Kai-Hang|KH|http://orcid.org/0000-0003-2145-3108']
D000368:Aged D001145:Arrhythmias, Cardiac D003924:Diabetes Mellitus, Type 2 D005260:Female D006333:Heart Failure D006801:Humans D008297:Male D008875:Middle Aged D016032:Randomized Controlled Trials as Topic D051436:Renal Insufficiency, Chronic D018570:Risk Assessment D012307:Risk Factors D000077203:Sodium-Glucose Transporter 2 Inhibitors D016896:Treatment Outcome
Arrhythmia Atrial fibrillation SGLT2 inhibitors