Effect of the cardiac myosin activator omecamtiv mecarbil on ventricular arrhythmias, cardiac arrest, and sudden death in heart failure with reduced ejection fraction: the GALACTIC-HF trial

Aims Omecamtiv mecarbil (OM) has been shown to benefit individuals with heart failure and reduced ejection fraction but the clinical experience of cardiac myosin activators and risk of life-threatening ventricular arrhythmias (VA) is limited. We investigated the effects of OM on incidence of VA, cardiac arrest, and sudden death (SD) in the GALACTIC-HF trial. Methods GALACTIC-HF was a placebo-controlled randomized trial testing the efficacy and safety of OM in participants with symptomatic chronic HF and LVEF ≤35%. Ventricular arrhythmias and cardiac arrest were investigator-reported adverse events while SD was centrally adjudicated. Severe HF was defined according to the ESC-HFA criteria. The effect of OM on the composite of the first occurrence of serious VA, cardiac arrest, or SD was examined using Cox proportional hazards models. Results Over a median follow-up of 21.8 months, 706 out of the 8232 participants randomized in the GALACTIC-HF trial experienced serious VA, cardiac arrest, or SD. Randomization to OM led to a trend towards reduced risk for the composite arrhythmic outcome (377 events in the placebo group vs. 329 in the OM study arm; HR 0.86; 95% CI 0.75–1.00; P = .054). The strength of the association between OM and lower risk of composite events was stronger in participants with an LVEF ≤the median level of 28% (HR 0.77; 95% CI 0.63–0.94; P = .009) and appeared consistent in participants with severe HF. Conclusion In this post hoc analysis of the GALACTIC-HF trial, we observed a potential reduction in life-threatening arrhythmia, cardiac arrest, and SD with OM treatment, especially in patients with severely reduced LVEF. These findings require prospective validation in the ongoing COMET-HF trial.