Association between age or duration of diagnosis in obstructive hypertrophic cardiomyopathy and response to mavacamten treatment: Exploratory analysis of the EXPLORER-HCM trial.

Background and aims: In patients with symptomatic, obstructive hypertrophic cardiomyopathy (HCM), it is unclear if response to cardiac myosin inhibition varies with older age or a longer duration of diagnosis. This study evaluated the response of these subgroups to mavacamten therapy for all primary, secondary, and exploratory endpoints in the EXPLORER-HCM trial (ClinicalTrials.gov: NCT03470545).

Methods: Patients were stratified by age (≤60 vs. >60 years) and duration of HCM diagnosis (≤5 vs. >5 years). To estimate treatment differences and evaluate age and diagnosis duration by treatment interaction, analysis of covariance was used to model changes in continuous endpoints and a generalized linear model was used for binary endpoints.

Results: Older patients were more frequently female (53% vs. 29%), with a lower prevalence of pathogenic/likely pathogenic HCM gene variants (17% vs. 36%), lower mean peak oxygen consumption (pVO₂) (17.6 vs. 21.1 ml/kg/min), and a higher mean NT-proBNP level (817 vs. 592 ng/L) but similar NYHA classes and quality of life scores. Patients with a longer vs. shorter diagnosis duration had similar mean ages (59.0±11.6 vs. 57.9±12.3 years) but more family history of HCM (38% vs. 16%) and a higher mean NT-pro BNP level (938±118 vs. 494±145 ng/ml). No differences were observed in improvement in peak oxygen consumption, NYHA class, or patient-reported outcomes among older patients and those with a longer duration of diagnosis.

Conclusions: In EXPLORER-HCM, mavacamten treatment had a similar benefit for all primary, secondary, and exploratory endpoints in patients with symptomatic, obstructive HCM regardless of age or duration of diagnosis.