NYU Langone Health Med-Lit Review
Clinical Question: Is aficamten monotherapy superior to metoprolol monotherapy for patients with symptomatic obstructive hypertrophic cardiomyopathy?
Background: Aficamten is a novel drug that functions as a selective cardiac myosin inhibitor. It has been shown to decrease hypercontractility and improve symptoms in patients with symptomatic hypertrophic cardiomyopathy. Beta-blockers have been the recommended initial treatment prior to aficamten’s development. However, there has been limited evidence of aficamten’s benefit.
Study Design: Double blind, double-dummy trial
Setting: International at 71 sites in North America, Brazil, Europe, Israel, and China
Synopsis: This was a phase 3, double blind, double-dummy randomized trial done from June 2023 to August 2024. 281 patients were screened for eligibility across 71 international sites, with ultimately 175 meeting participation criteria. 88 were randomly assigned to the aficamten group and 87 to the metoprolol group. The mean age of the patients was 58 years, 58.3% were men, and the mean left ventricular outflow tract gradient was 47 mmHg at rest and 74 mmHg after the Valsalva maneuver. After 24 weeks, patients in the aficamten group had statistically significant improvement in peak oxygen uptake compared to the metoprolol group. They also were observed to have improvement in New York Heart Association class, Kansas City Cardiomyopathy Questionnaire scores, and left ventricular outflow gradient compared to the metoprolol group. Adverse event rates were similar in both groups. Sample size is a significant limitation in this study, and further replication and validation of these results with a larger number of participants would help in providing greater evidence supporting this study’s conclusions.
Bottom Line: Aficamten’s more targeted approach at inhibiting cardiac myosin and reducing hypercontractility appears to be superior to beta-blockers such as metoprolol for symptomatic obstructive hypertrophic cardiomyopathy.
Citation: Garcia-Pavia P, et al. Aficamten or metoprolol monotherapy for obstructive hypertrophic cardiomyopathy. N Engl J Med. 2025;393(10):949-960. doi: 10.1056/NEJMoa2504654.
Video: View Dr. Hasan’s video review.
Dr. Hasan is a board-certified hospitalist in the department of hospital medicine at NYU Langone Hospital–Brooklyn in New York and a clinical assistant professor of medicine in the department of medicine at NYU Grossman School of Medicine in New York.