Physicians' Academy for Cardiovascular Education

Longer-term safety and efficacy results with cardiac myosin inhibitor in obstructive HCM

News - Nov. 8, 2022

Myosin Inhibition in Patients With Obstructive HCM Referred for Septal Reduction Therapy: 32-Week Active Blinded Crossover Results From VALOR-HCM Trial

Presented at the AHA Scientific Sessions 2022 by: Prof. Milind Desai, MD - Cleveland, OH, USA

Introduction and methods

Mavacamten is a selective cardiac myosin inhibitor that targets the underlying pathophysiology of obstructive hypertrophic cardiomyopathy (HCM). The VALOR-HCM trial recently showed that mavacamten significantly reduced the proportion of patients who were eligible for, or choose to receive, septal reduction therapy (SRT) at 16 weeks in patients with symptomatic obstructive HCM. The current pre-specified study of the VALOR-HCM trial investigated the effects of mavacamten through 32 weeks of dose-blinded treatment in patients originally randomized to mavacamten who continued the drug (exposure of day 1 to week 32) and in patients originally randomized to placebo who crossed over to dose-blinded mavacamten at week 16 (exposure from week 16 to week 32).

VALOR-HCM included patients ≥ 18 years of age with obstructive HCM with severe symptoms (NYHA class III/IV or Class II with exertional syncope or near syncope) despite maximally-tolerated medical therapy. All patients have been referred for SRT within the past 12 months and were actively considering the procedure. Patients could choose to proceed with SRT at any time during the study. A total of 112 patients were randomized to receive either mavacamten (n=56) or placebo (n=56) for 16 weeks.

After 16 weeks, patients originally randomized to mavacamten continued on the same dose they were on in week 16 (2.5, 5, 10, or 15 mg once a day, n=56) and patients originally randomized to placebo crossed over to mavacamten at a starting dose of 5 mg daily (n=52). All patients underwent monthly echo examinations. In the crossover group, dose titration was performed at 24 weeks (2.5, 5, or 10 mg) and 28 weeks (2.5, 5, 10 or 15 mg). Titration was based on echo measures of LVEF and LVOT gradient at rest and Valsalva provocation. At week 32, endpoints were evaluated using echo, stress echo and SRT evaluation. The primary composite endpoint was the patients’ decision to proceed with SRT or eligibility for SRT according to the 2011 AHA/ACC guidelines. Key secondary endpoints included change in NYHA functional class, change in resting and Valsalva LVOT gradient, change in KCCQ-CSS, and change in biomarkers (NT-proBNP and cardiac troponin I) and echocardiographic parameters (LV mass index and median septal E/e’) from baseline to 32 weeks.

Main results

Primary outcome

Secondary outcomes



In patients with highly symptomatic obstructive HCM who were referred for SRT, mavacamten

reduced the need for SRT at 32 weeks with sustained improvements in LVOT gradients, quality of live as measured by KCCQ-CSS, NT-proBNP, troponin I, and LV mass index and E/e’ ratio. Similar improvements were seen in patients who crossed over from placebo to mavacamten after 16 weeks. Mavacamten was generally well tolerated.

-Our reporting is based on the information provided at the AHA Scientific Sessions-

The results of this study were simultaneously published in Circulation.

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