Mavacamten is the first cardiac myosin inhibitor to receive worldwide approval for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) classified as New York Heart Association (NYHA) functional class II–III. By directly targeting the hypercontractile phenotype underlying the pathophysiology of the disease, mavacamten has demonstrated consistent benefits in phase 2 and 3 studies, including a reduction of left ventricular outflow tract (LVOT) gradient, improvements in exercise capacity, symptoms, and quality of life, as well as evidence of favorable cardiac remodeling on multimodal imaging. An individualized, echocardiography-guided dosing strategy has been developed to optimize efficacy while minimizing the risk of left ventricular ejection fraction reduction. Mavacamten also decreases the proportion of patients meeting guideline criteria for septal reduction therapy. Mavacamten is primarily metabolized by CYP2C19 (cytochrome P450 2C19), with the enzyme phenotype determining the degree of drug exposure. Nevertheless, its use has been shown to have a favorable safety profile regardless of the patient’s metabolic status. Dose titration takes into account the risk of systolic dysfunction in the setting of comorbid conditions, as well as potential drug–drug interactions with inhibitors and substrates of the cytochrome P450 system. This article reviews the available efficacy and safety data from completed and ongoing clinical studies of mavacamten in patients with symptomatic oHCM. Ongoing long-term studies aim to clarify its role within therapeutic algorithms, its interaction with background therapies, and its potential to modify disease progression beyond symptomatic relief.
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