Cardiac myosin inhibition in hypertrophic cardiomyopathy: review of the evolving evidence base

INTRODUCTION: There is an unmet need for effective medical therapies in the treatment of obstructive hypertrophic cardiomyopathy (HCM). This is changing with emergence of cardiac myosin inhibitors (CMI), which reduce cardiac myocyte hypercontractility, normalize left ventricular function, and reduce left ventricular outflow tract obstruction. Mavacamten and aficamten are the first 2 drugs in this class with high-quality phase III randomized clinical trial data (Based on PUBMED search, last query April 2025). AREAS COVERED: In the current review, we perform a detailed analysis of the background characteristics, primary endpoints, efficacy, and safety data available from 4 phase III randomized trials in which mavacamten and aficamten were tested against placebo. This includes understanding clinically meaningful class-based effects vs. specific drug differences. EXPERT OPINION: CMI therapy represents an exciting evolution in management of HCM patients, targeting for the first time the underlying pathophysiologic mechanisms of the disease. There is a growing body of evidence based on high-quality scientific investigation that are broadening the therapeutic options for patients with this condition. However, as different drugs emerge in the same class, it is crucial to appreciate clinically meaningful class-based effects vs. specific drug differences.