Exploring the risk of ventricular arrhythmia and sudden cardiac death with SGLT2 inhibitors in heart failure patients: a comprehensive systematic review and bayesian network meta-analysis

Abstract Background SGLT2 inhibitors have emerged as a promising treatment for heart failure, with evidence suggesting benefits in reducing hospitalizations and improving survival. However, concerns regarding their potential to induce ventricular arrhythmia and the risk of sudden cardiac death (SCD) remain largely unexplored. This study aims to address these concerns by analyzing the risk of these adverse events in heart failure patients treated with SGLT2 inhibitors. Objectives To assess the risk of ventricular arrhythmia and sudden cardiac death in heart failure patients using SGLT2 inhibitors through a Bayesian network meta-analysis. Methods We conducted a Bayesian network meta-analysis to evaluate the risk of ventricular arrhythmia and sudden cardiac death (SCD) in heart failure patients treated with SGLT2 inhibitors. Randomized controlled trials (RCTs) were identified through systematic searches of PubMed, Embase, and Scopus. Both dichotomous outcomes (risk ratios, RR) for ventricular arrhythmia and time-to-event outcomes (hazard ratios, HR) for SCD were assessed with 95% credible intervals (CrI). A random-effects model was used to account for variability among studies, with SGLT2 inhibitors as the primary interventions of interest and placebo or standard treatment as the control. Surface under the cumulative ranking curve (SUCRA) values were used to rank the interventions. Bayesian analysis was performed using Markov Chain Monte Carlo (MCMC) methods, and convergence was evaluated through trace plots and the Gelman-Rubin diagnostic. Results We analyzed data from 73,963 patients across 22 RCTs. For the primary outcome, the risk of sudden cardiac death (SCD), the interventions were ranked as follows: Empagliflozin ranked highest (HR: 0.70, 95% CrI: 0.40 to 1.14; SUCRA: 73.34%), followed by Canagliflozin (HR: 0.72, 95% CrI: 0.40 to 1.14; SUCRA: 71.55%), Dapagliflozin (HR: 0.73, 95% CrI: 0.48 to 1.06; SUCRA: 69.77%), Ertugliflozin (HR: 1.66, 95% CrI: 0.25 to 5.92; SUCRA: 33.86%), Control (SUCRA: 29.65%), and Sotagliflozin (HR: 1.27, 95% CrI: 0.60 to 2.35; SUCRA: 21.82%). For the risk of ventricular arrhythmia, Bexagliflozin was ranked the most effective (RR: 0.33, 95% CrI: 0.07 to 0.94; SUCRA: 91.79%), followed by Canagliflozin (RR: 0.50, 95% CrI: 0.21 to 0.96; SUCRA: 78.29%), Sotagliflozin (RR: 0.76, 95% CrI: 0.31 to 1.56; SUCRA: 52.59%), Empagliflozin (RR: 0.79, 95% CrI: 0.41 to 1.10; SUCRA: 45.20%), Ertugliflozin (RR: 0.92, 95% CrI: 0.47 to 1.62; SUCRA: 34.53%), Dapagliflozin (RR: 0.92, 95% CrI: 0.61 to 1.41; SUCRA: 32.27%), and Control (SUCRA: 15.34%). Conclusion This Bayesian network meta-analysis suggests that SGLT2 inhibitors, particularly Empagliflozin and Canagliflozin, are associated with a lower risk of sudden cardiac death and ventricular arrhythmia in heart failure patients. Bexagliflozin also shows promise for reducing ventricular arrhythmia. Further studies are needed to confirm these findings.Forest plots of outcomes of interest League table of ventricular arrhythmia