Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

BACKGROUND: Improving symptoms is a primary treatment goal in patients with obstructive hypertrophic cardiomyopathy. Currently available pharmacological options for hypertrophic cardiomyopathy are not disease-specific and are often inadequate or poorly tolerated. We aimed to assess the effect of mavacamten, a first-in-class cardiac myosin inhibitor, on patients' health status-ie, symptoms, physical and social function, and quality of life. METHODS: We did a health status analysis of EXPLORER-HCM, a phase 3, double-blind, randomised, placebo-controlled trial. The study took place at 68 clinical cardiovascular centres in 13 countries. Adult patients (≥18 years) with symptomatic obstructive hypertrophic cardiomyopathy (gradient ≥50 mm Hg and New York Heart Association class II-III) were randomly assigned (1:1) to mavacamten or placebo for 30 weeks, followed by an 8-week washout period. Both patients and staff were masked to study treatment. The primary outcome for this secondary analysis was the Kansas City Cardiomyopathy Questionnaire (KCCQ), a well validated disease-specific measure of patients' health status. It was administered at baseline and weeks 6, 12, 18, 30 (end of treatment), and 38 (end of study). Changes from baseline to week 30 in KCCQ overall summary (OS) score and all subscales were analysed using mixed model repeated measures. This study is registered with ClinicalTrials.gov, NCT03470545. FINDINGS: Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned. Of 123 patients randomly assigned to mavacamten, 92 (75%) completed the KCCQ at baseline and week 30 and of the 128 patients randomly assigned to placebo 88 (69%) completed the KCCQ at baseline and week 30. At 30 weeks, the change in KCCQ-OS score was greater with mavacamten than placebo (mean score 14·9 [SD 15·8] vs 5·4 [13·7]; difference +9·1 [95% CI 5·5-12·8]; p