Cardiac Myosin Inhibitors: Expanding the Horizon for Hypertrophic Cardiomyopathy Management

Abstract

Objective: To review the current literature on the efficacy and safety of cardiac myosin inhibitors (CMIs) for the treatment of hypertrophic cardiomyopathy (HCM).

Data sources: A literature search was conducted on PubMed from origin to April 2023, using the search terms "MYK-461," "mavacamten," "CK-3773274," and "aficamten." Studies were limited to English-based literature, human subjects, and clinical trials resulting in the inclusion of 13 articles. ClinicalTrials.gov was also used with the same search terms for ongoing and completed trials.

Study selection and data extraction: Only phase II and III studies were included in this review except for pharmacokinetic studies that were used to describe drug properties.

Data synthesis: CMIs enable cardiac muscle relaxation by decreasing the number of myosin heads that can bind to actin and form cross-bridges. Mavacamten, the first Food and Drug Administration (FDA)-approved drug in this class, has been shown to improve hemodynamic, functional, and quality of life measures in HCM with obstruction. In addition, aficamten is likely to become the next FDA-approved CMI with promising phase II data and an ongoing phase III trial expected to release results in the next year.

Relevance to patient care and clinical practice in comparison with existing drugs: CMIs provide a novel option for obstructive hypertrophic cardiomyopathy, particularly in those not suitable for septal reduction therapy. Utilization of these agents requires knowledge of drug interactions, dose titration schemes, and monitoring parameters for safety and efficacy.

Conclusions: CMIs represent a new class of disease-specific drugs for treatment of HCM. Cost-effectiveness studies are needed to delineate the role of these agents in patient therapy.

Keywords: aficamten; cardiac myosin inhibitor; hypertrophic cardiomyopathy; left ventricular outflow obstruction; mavacamten.