Association between sodium–glucose cotransporter-2 inhibitors and risk of sudden cardiac death or ventricular arrhythmias: a meta-analysis of randomized controlled trials

• Published in: Europace (London, England) Vol. 24; no. 1; pp. 20 - 30
• Main Authors: Sfairopoulos, Dimitrios, Zhang, Nan, Wang, Yueying, Chen, Ziliang, Letsas, Konstantinos P, Tse, Gary, Li, Guangping, Lip, Gregory Y H, Liu, Tong, Korantzopoulos, Panagiotis
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 04.01.2022
• Subjects: Arrhythmias, Cardiac - complications; Death, Sudden, Cardiac - epidemiology; Death, Sudden, Cardiac - etiology; Death, Sudden, Cardiac - prevention & control; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - drug therapy; Glucose - therapeutic use; Humans; Randomized Controlled Trials as Topic; Sodium; Sodium-Glucose Transporter 2 Inhibitors - adverse effects; Ventricular arrhythmias; Heart failure; Sodium–glucose cotransporter-2 inhibitors; Sudden death; Diabetes mellitus; Meta-analysis
• ISSN: 1099-5129; 1532-2092; 1532-2092
• DOI: 10.1093/europace/euab177

Abstract Aims  Sudden cardiac death (SCD) and ventricular arrhythmias (VAs) are important causes of mortality in patients with type 2 diabetes mellitus (T2DM), heart failure (HF), or chronic kidney disease (CKD). We evaluated the effect of sodium–glucose cotransporter-2 (SGLT2) inhibitors on SCD and VAs in these patients. Methods and results  We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that enrolled patients with T2DM and/or HF and/or CKD comparing SGLT2i and placebo or active control. PubMed and ClinicalTrials.gov were systematically searched until November 2020. A total of 19 RCTs with 55 ,590 participants were included. Sudden cardiac death events were reported in 9 RCTs (48 patients receiving SGLT2i and 57 placebo subjects). There was no significant association between SGLT2i therapy and SCD [risk ratio (RR) 0.74, 95% confidence interval (CI) 0.50–1.08; P = 0.12]. Ventricular arrhythmias were reported in 17 RCTs (126 patients receiving SGLT2i and 134 controls). SGLT2i therapy was not associated with a lower risk of VAs (RR 0.84, 95% CI 0.66–1.06; P = 0.14). Besides the subgroup of low-dosage SGLT2i therapy that demonstrated decreased VAs compared to control (RR 0.45, 95% CI 0.25–0.82; P = 0.009), or to placebo (RR 0.46, 95% CI 0.25–0.85; P = 0.01), further subgroup analysis did not demonstrate any significant differences. Conclusion  SGLT2i therapy was not associated with an overall lower risk of SCD or VAs in patients with T2DM and/or HF and/or CKD. However, further research is needed since the number of SCD and VA events were relatively few leading to wide confidence intervals, and the point estimates suggested potential benefits.