Redefining outcomes of ventricular arrhythmia for SGLT2 inhibitor medication in heart failure patients: a meta-analysis of randomized controlled trials.

Summary

This PROSPERO-registered meta-analysis of 23 RCTs (n=74,380) found SGLT2 inhibitors significantly reduce ventricular arrhythmias (RR 0.85) and sudden cardiac death (RR 0.79). Benefits persisted with ≥1-year follow-up and across HF phenotypes and related cardiometabolic conditions.

Key Findings

• Across 23 RCTs (n=74,380), SGLT2 inhibitors reduced ventricular arrhythmias (RR 0.85, 95% CI 0.74–0.98).
• SGLT2 inhibitors reduced sudden cardiac death (RR 0.79, 95% CI 0.64–0.98).
• Benefits persisted with ≥1-year follow-up and across T2D, CVD, HFrEF, HFpEF, and HFmrEF subgroups.

Clinical Implications

Clinicians can consider SGLT2 inhibitors as part of a comprehensive strategy to reduce VA/SCD risk across HF phenotypes, while awaiting dedicated arrhythmia-focused trials. This supports early initiation in eligible HF patients.

Limitations

• Arrhythmia outcomes were not primary endpoints in most included trials, risking event ascertainment variability
• Clinical heterogeneity across populations, agents, and follow-up durations

Future Directions

Conduct dedicated RCTs with arrhythmia and SCD as primary endpoints, and mechanistic studies to delineate antiarrhythmic pathways of SGLT2 inhibitors.