Impact of SGLT-2 inhibitors on ventricular arrhythmias and cardiovascular mortality in patients with heart failure and ICD or CRT devices: a systematic review and meta-analysis

Background

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have demonstrated cardiovascular benefits in patients with heart failure (HF). However, their role in reducing ventricular tachyarrhythmias (VTs) and cardiovascular (CV) mortality among advanced heart failure patients with implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy devices (CRT/CRT-D) remains underexplored.

Purpose

We aim to evaluate the impact of SGLT-2 inhibitors on VT events, and CV mortality in this population.

Methods

A systematic literature search was performed using PubMed, Ovid MedLine, and Cochrane Library to identify RCTs and observational studies comparing SGLT-2 inhibitors to placebo or furosemide in heart failure patients with an ICD or CRT/CRT-D device. A random-effects meta-analysis was conducted to estimate incidence rate ratios (IRRs) for sustained and non-sustained VT/VF, and odds ratios (ORs) for cardiovascular mortality. Heterogeneity was assessed using the I² statistic. A leave-one-out sensitivity analysis evaluated the influence of individual studies.

Results

Five studies involving 14,259 patients were included. Use of SGLT-2 inhibitors was associated with a significant reduction in ventricular tachyarrhythmia events (IRR = 0.49, 95% CI: 0.24-0.98, p = 0.043, I² = 96.6%) (A). In a leave-one-out sensitivity analysis, excluding Katov et al., the pooled IRR was 0.39 (95% CI: 0.19-0.77, p = 0.007, I² = 97.4%) (B). SGLT-2 inhibitors were also associated with a significantly lower risk of cardiovascular mortality (OR= 0.20, 95% CI: 0.19-0.21, p = 0.002, I² = 0%) (C).

Conclusion

Our meta-analysis suggests that SGLT-2 inhibitors significantly reduce the risk of ventricular tachyarrhythmia events and cardiovascular mortality in patients with heart failure and ICD or CRT/CRT-D devices. These findings support the expanding role of SGLT-2 inhibitors as part of comprehensive arrhythmia and mortality risk reduction strategies in advanced heart failure populations.

Figure 1. Forest Plots of SGLT-2 Inhibitors and Clinical Outcomes in Heart Failure Patients with ICD or CRT Devices (A) Forest plot of pooled incidence rate ratio (IRR) for ventricular tachyarrhythmia (VT) events. (B) Forest plot of leave-one-out sensitivity analysis for VT events excluding Katov et al. (C) Forest plot of pooled odds ratio (OR) for cardiovascular (CV) mortality.Figure 1.