Reviwer : Dr. Oğuzhan Birdal

Name of Study : Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM)

Published congress : ACC 2021

Fulltext link: https://www.thelancet.com/article/S0140-6736(20)31792-X/fulltext

Background :
Hypertrophic Cardiomyopathy is a primary myocardial disease characterized by unexplained left ventricular hypertrophy caused by pathogenic variants of sarcomeric genes. The main goal of treatment is symptomatic improvement. However, current treatment options are not specific and sufficient for this disease. Mavacamten is a direct myosin inhibitory agent that reduces contractility.

Objective :
In this study the effect of mavacamten on the health status (such as symptoms, quality of life) of patients with obstructive hypertrophic cardiomyopathy was investigated.

Methods :
The study was designed as a multicenter, randomized, double-blind, placebo-controlled study. Patients over 18 years of age , with a left ventricular outflow tract gradient >50 mmHg and a functional capacity class 2-3 according to the New York Heart Association were included in the study. During the 30-week period, patients were randomized (1:1) to the mavacamten and placebo arms. After this period, no medication was given for 8 weeks and the results were analysed. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was used at baseline,  6, 12, 18, 30 (end of treatment), and 38 weeks (end of study) to examine the changes in patients’ health status.

Results :
92 (75%) of 123 patients in the Mavacamten arm and 88 (69%) of 128 patients in the placebo arm completed KCCQ at baseline and at week 30. At 30 weeks, the change in KCCQ mean score was significantly higher in the mavacamten arm than in placebo (p=<0.0001). The proportion of patients with very large change (KCCA mean score ≥20 points) was 36% (33 out of 92) in the mavacamten group versus 15% (13 out of 88) in the placebo group.

Conclusion :
Mavacamten provides significant improvement in the healt status of patients with obstructive hypertrophic cardiomyopathy. The benefits are observed in the early period after starting the treatment. Benefits regress with discontinuation of treatment.

Interpretations :
Considering the fact that the primary goals in the treatment of patients with obstructive hypertrophic cardiomyopathy are to reduce symptoms, improve physical and social functions, and improve quality of life, mavacamten may be a new therapeutic agent that can be used to achieve these goals.