Effect of Mavacamten in Women Compared With Men With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM.

Background: Compared with men, women with hypertrophic cardiomyopathy (HCM) have a higher incidence of heart failure and worse outcomes. We investigated baseline clinical and echocardiographic characteristics and response to mavacamten among women compared with men in the EXPLORER-HCM study (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy).
Methods: A prespecified post hoc analysis of sex from the blinded, randomized EXPLORER-HCM trial of mavacamten versus placebo in symptomatic patients with obstructive HCM was performed. Baseline characteristics were compared with t tests for continuous variables (expressed as mean values) and χ ² tests for categorical variables. Prespecified primary, secondary, and exploratory end points and echocardiographic measurements from baseline to end of treatment (week 30) were analyzed with ANCOVA for continuous end points and a generalized linear model with binomial distribution for binary end points, with adjustment for each outcome's baseline value, New York Heart Association class, β-blocker use, and ergometer type.
Results: At baseline, women (n=102) were older (62 years versus 56 years; P <0.0001), had lower peak oxygen consumption (16.7 mL·kg ^-1 ·min ^-1 versus 21.3 mL·kg ^-1 ·min ^-1 ; P <0.0001), were more likely to be assigned New York Heart Association class III (42% versus 17%; P <0.0001), had worse health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 64 versus 75; P <0.0001), and had higher baseline plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels (1704 ng/L versus 990 ng/L; P =0.004) than men (n=149). After 30 weeks of mavacamten treatment, similar improvements were observed in women and men in the primary composite end point (percentage difference on mavacamten versus placebo, 22% versus 19%, respectively; P =0.759) and in the secondary end points of change in postexercise left ventricular outflow tract gradient (-42.4 mm Hg versus -33.6 mm Hg; P =0.348), change in peak oxygen consumption (1.2 mL·kg ^-1 ·min ^-1 versus 1.6 mL·kg ^-1 ·min ^-1 ; P =0.633), and percentage achieving ≥1 New York Heart Association class improvement (41% versus 28%; P =0.254). However, women had greater improvement in health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 14.8 versus 6.1; P =0.026) and in the exploratory end point of NT-proBNP levels (-1322 ng/L versus -649 ng/L; P =0.0008).
Conclusions: Although at baseline women with symptomatic obstructive HCM enrolled in EXPLORER-HCM were older and had worse heart failure and health status than men, treatment with mavacamten resulted in similar improvements in the primary and most secondary EXPLORER-HCM end points and greater improvements in health status and NT-proBNP.
Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03470545.
Competing Interests: Disclosures Dr Cresci reports institution research funding for clinical trial from Imbria Pharmaceuticals and serving on the Data Monitoring Committee for Cytokinetics. Dr Bach reports institution research funding for clinical trials from BMS and Cytokinetics. Dr Saberi reports consulting for Cytokinetics and BMS. Dr Owens reports consulting for BMS, Cytokinetics, Pfizer, Tenaya, Renovacor, Stealth, Edgewise, Lexicon, and Biomarin. Dr Spertus reports consulting on patient-reported outcomes and evidence evaluation for Alnylam, AstraZeneca, Bayer, Merck, Janssen, BMS, Edwards, Kineksia, 4DT Medical, Terumo, Cytokinetics, Imbria, and United Healthcare; receiving research grants from BMS, Abbott Vascular, and Janssen; holding copyright to the Seattle Angina Questionnaire, KCCQ, and Peripheral Artery Questionnaire; and serving on the Board of Directors for Blue Cross Blue Shield of Kansas City. Dr Hegde reports fees paid to institution for core laboratory services from Myokardia/BMS. Dr Lakdawala reports consulting for BMS, Cytokinetics, Tenaya, Pfizer, and Akros and receiving research support from BMS and Pfizer. Dr Nilles and D.M. Wojdyla report no conflicts. Dr Sehnert is an employee of BMS and owns stock/stock grants from BMS. Dr Wang reports research grant to institution from BMS and Cytokinetics and serving on the Advisory Board (consultant) for BMS, Cytokinetics, and BioMarin and speakers’ bureau for BMS.