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Cardiomyopathies

Cardiac myosin inhibitors for the treatment of obstructive and non-obstructive HCM

Nature Reviews Cardiology volume 22, page 840 (2025)Cite this article

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Two late-breaking clinical trials presented at the ESC Congress 2025 and published in The New England Journal of Medicine have explored the efficacy of cardiac myosin inhibitors for the treatment of hypertrophic cardiomyopathy (HCM). First, although the cardiac myosin inhibitor mavacamten has been approved to treat symptomatic obstructive HCM, the ODYSSEY-HCM trial investigators now report that the drug does not improve peak oxygen uptake or reduce symptoms compared with placebo in patients with non-obstructive HCM. Moreover, the investigators in the MAPLE-HCM trial show that in patients with obstructive HCM, aficamten is superior to the β-blocker metoprolol in increasing peak oxygen uptake and reducing symptoms.

In this phase III, double-blind, multicentre, randomized, placebo-controlled trial, a total of 580 adult patients (mean age 56 years; 46% women) with non-obstructive HCM were randomly assigned to mavacamten treatment or placebo. From baseline to week 48, the difference between groups in peak oxygen uptake was not significant (0.47 ml/kg/min, 95% CI −0.03 to 0.98, P = 0.07). Furthermore, the between-group difference in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) was also not significant (2.7 points, 95% CI −0.1 to 5.6, P = 0.06). Given that the symptoms experienced by patients with non-obstructive HCM are related to diastolic dysfunction and impaired cellular energetics, the investigators propose that cardiac myosin inhibitors might have a limited effect in improving haemodynamics or energy efficiency. A secondary analysis of the ODYSSEY-HCM data published in the Journal of the American College of Cardiology revealed that mavacamten was associated with improvements in cardiac biomarkers and favourable cardiac remodelling compared with placebo; these findings warrant further investigation into the efficacy of mavacamten in this patient cohort.

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  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Karina Huynh

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  1. Karina Huynh
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Correspondence to Karina Huynh.

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Huynh, K. Cardiac myosin inhibitors for the treatment of obstructive and non-obstructive HCM. Nat Rev Cardiol 22, 840 (2025). https://doi.org/10.1038/s41569-025-01218-y

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