OMECAMTIV MECARBIL Cardiac Myosin Activator Treatment of Heart Failure

Positive inotropic agents are used in the treatment of heart failure. Intravenous inotropes (dopamine, dobutamine, milrinone) improve the hemodynamic and clinical status of acute decompensated chronic heart failure, but they also increase intracellular concentrations of Ca2+ and cAMP, leading to increased myocardial oxygen demands, hypotension, arrhythmias and mortality. In chronic heart failure, the limited benefits, complex pharmacology and narrow therapeutic window have relegated the use of digoxin. Cardiac myosin activators are a new class of inotropic agents that increase systolic ejection time at concentrations at which they do not modify the intracellular calcium or cAMP levels. Omecamtiv mecarbil is the first drug of this class. In animal models, healthy volunteers and phase II clinical trials in patients with stable chronic heart failure, it increased the systolic ejection time, fractional shortening, stroke volume and cardiac output without altering myocardial oxygen, thus improving cardiac efficiency. In this article, we review the preclinical and clinical pharmacological properties of omecamtiv mecarbil. The results of clinical trials suggest that omecamtiv mecarbil may represent an effective and probably safer alternative to conventional inotropics in the treatment of heart failure patients. The future development of this compound is also discussed.