Omecamtiv mecarbil in heart failure with reduced ejection fraction: mechanisms, evidence, and therapeutic positioning

ABSTRACT

Heart failure with reduced ejection fraction (HFrEF) remains a major global challenge despite advances in neurohormonal therapies, which do not directly improve myocardial contractility. Omecamtiv mecarbil (OM), a first-in-class cardiac myosin activator, offers a novel mechanism by enhancing sarcomere function without raising intracellular calcium or oxygen demand, differentiating it from traditional inotropes. This narrative review synthesizes current evidence on OM’s pharmacology, preclinical data, and clinical trials. Preclinical studies demonstrated improved contractility with preserved energetic efficiency. Phase I–II trials confirmed dose-dependent improvements in systolic function with good tolerability. The Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial showed modest but significant reductions in heart failure events, especially in patients with severely reduced ejection fraction. However, OM’s limited effect on functional capacity and narrow therapeutic window necessitate selective use. Positioned as an adjunctive option for patients with advanced systolic dysfunction, OM’s future utility may be enhanced by biomarker-guided strategies, simplified dosing, and combination regimens.

Keywords: Omecamtiv Mecarbil; heart failure, systolic; myocardial contraction; myosins; cardiotonic agents; inotropic agents; ventricular dysfunction, left; clinical trials; GALACTIC-HF; COSMIC-HF