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

Abstract 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.