Abstract
BackgroundCardiac 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.MethodsMEDLINE, 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.ResultsOut 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.ConclusionsSGLT2i 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.
Highlights
Cardiac arrhythmias are associated with poorer outcomes in patients with heart failure (HF), diabetes mellitus (DM), and chronic kidney disease (CKD)
AF atrial fibrillation, AFL atrial flutter, VT ventricular tachycardia, Relative risks (RR) risk ratio, 95% confidence intervals (CI) 95% confidence interval, Phetero P-value for between-subgroup heterogeneity, DM diabetes mellitus, CKD chronic kidney disease, HF heart failure, ASCVD atherosclerotic cardiovascular disease was identified (p = 0.39 and p = 0.78 for AF and embolic stroke, respectively)
In this systematic review and meta-analysis of 22 trials with 52,115 patients with DM, CKD, or HF susceptible to developing arrhythmias, we found that sodium-glucose cotransporter 2 inhibitors (SGLT2i) treatment might be associated with a lower risk of AF, embolic stroke, AF/AFL, and VT, compared to placebo
Summary
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. A recent secondary analysis of the DECLARE-TIMI 58 trial (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) found that dapagliflozin reduced the risk of AF and atrial flutter (AFL) by 19% in susceptible patients with DM, compared to placebo [17]. Recent real-world studies have shown inconsistent conclusions: while SGLT2i were associated with a lower incidence of new-onset arrhythmias and AF, [20, 21] the CVD-REAL Nordic study [22] showed neutral association. The association between SGLT2i and arrhythmia outcomes remains uncertain
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