1. Compared to placebo, patients treated with mavacamten for 30 weeks showed significant improvements on the KCC Questionnaire which evaluates health status and quality of life.
2. In patients with symptomatic hypertrophic cardiomyopathy, the number needed to treat with mavacamten was 5.
Evidence Rating Level: 2 (Good)
Study Rundown: The EXPLORER-HCM phase III drug trial (2020) found that mavacamten significantly improves patients’ clinical outcomes, such as exercise capacity, NYHA functional class and left ventricular outflow tract (LVOT) obstruction pressure. While these objective measures are essential to document in clinical trials, a patient’s subjective experience and quality of life are also valuable to create a more holistic narrative. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was electronically taken by the patients of EXPLORER-HCM at weeks 6, 12, 18, 30 (end of treatment) and 38 (end of study) of the trial. The KCCQ reports a patient’s quality of life, social and physical function, and burden from their symptoms. Following 30 weeks of treatment, the mavacamten group had a significantly greater increase in KCCQ score compared to the placebo group. A greater proportion of patients on mavacamten showed large improvement on the KCCQ compared to patients given placebo. Additionally, benefits seen with mavacamten sharply diminished after treatment was stopped. Limitations of this study include missing data for 28% of the participants on week 30, due to suspected technical error. Nonetheless, this study provides meaningful information that can be easily communicated to patients when clinicians are considering mavacamten.
In-Depth [randomized controlled trial]: This article reports the health status findings of a larger phase III drug trial (EXPLORER-HCM) for mavacamten. EXPLORER-HCM is a double-blind, randomized control trial in 13 countries between May 30, 2018 to July 12, 2019. Eligibility criteria included adults with LVOT pressure gradients > 50mmHg and NYHA class II-III symptoms. Random assignment was done 1:1 for either mavacamten 5 mg (n=92) or placebo (n=88). EXPLORER-HCM reported on many endpoints, with the primary being clinical benefit (improvement in pVO2 and NYHA class reduction). This study reported on KCCQ-OSS. The 23-item Kansas City Cardiomyopathy Questionnaire evaluates six distinct domains: symptoms, physical function, quality of life, social limitation, self-efficacy, and symptom stability. It reports two final scores: clinical summary score (CSS) and overall summary (OSS). CSS reports only symptom and physical function, while OSS more holistically includes social and quality of life scores. Participants took this questionnaire electronically before other procedures at weeks 6, 12, 18, 30 (end of treatment), and 38 (end of study, post-medication). KCCQ scores are reported on a scale from 0-100, with 100 being the best.
At all follow-up points, there was a sustained benefit to KCCQ scores in the mavacamten group (mean score 14.9, [SD 15.8]) compared to the placebo (mean score 5.4 [13.7]; +9.1 increase to mean score at week 30, p<0.0001). Once treatment was stopped at week 38, there was a return to baseline KCCQ score in the mavacamten group with no significant difference between groups (p=0.084). All domains showed this separation between placebo and mavacamten, with physical limitation score being the most effected. In addition, a greater proportion of patients given mavacamten (36%) showed large improvements in KCCQ-OS (≥ 20 points) than placebo (15%; absolute difference = 21%, number needed to treat = 5).
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