Cardiac myosin inhibitor reduces need for septal reduction therapy in patients with obstructive HCM

VALOR-HCM 56 Week long-term extension study in oHCM

News - Sep. 4, 2023

Presented at the ESC Congress 2023 by: Milind Desai, MD - Cleveland, OH, USA

Introduction and methods

There is an unmet need for medical alternatives to septal reduction therapies (SRT) for patients with obstructive hypertrophic cardiomyopathy (oHCM). In the phase 3 EXPLORER-HCM and VALOR-HCM trials, the cardiac myosin inhibitor mavacamten reduced the need for SRT, and improved LVOT gradient, quality of life and physical functioning in patients with symptomatic oHCM. The VALOR-HCM trial was a placebo-controlled randomized trial for 16 weeks with a placebo to mavacamten cross over starting at week 16. In this long-term extension study of VALOR-HCM, the efficacy and safety of mavacamten was assessed at week 56 in 2 patient groups, namely in patients who were initially randomized to mavacamten in the trial (56 week exposure to mavacamten), and in patients who were initially randomized to placebo who crossed over to mavacamten at week 16 (40 weeks exposure to mavacamten).

In VALOR-HCM, adult symptomatic patients with oHCM were enrolled who were on maximally-tolerated medical therapies, and had a SRT referral. A total of 56 patients (48.2% female, 92.9% had a NYHA Class III or higher) were in the original mavacamten group, whereas 52 patients (51.9% female, 96.2% had NYHA Class III or higher) were in the placebo to mavacamten crossover group. From week 16, patients in the original mavacamten group were on their maximum dose concentration (2.5, 5, 10, or 15 mg once daily), whereas patients in the crossover group started a mavacamten uptitration schedule. Uptitration of mavacamten was based on clinical and ECG assessments. SRT evaluation was performed at baseline, week 16, week 32 and week 56. All patients were eligible for SRT at baseline.

The composite principal endpoint was patient decision to proceed with SRT, eligibility for SRT according to the 2011 AHA/ACC guidelines, or SRT status non-evaluable.

Main results


  • The principal SRT composite outcome occurred in 5 patients (8.0%) in the original mavacamten group and in 10 patients (19.2%) in the placebo to mavacamten crossover group.
  • At week 56, 6 patients decided to proceed with SRT (3 patients [5.4%] in the original mavacamten group and 3 patients [5.8%] in the crossover group).
  • 96 of 108 patients (89%) continued treatment with mavacamten in the long-term extension of this study without SRT.
  • NYHA Class improvement of at least 1 at week 56 was achieved by 93% and 73% of patients in the original mavacamten group and crossover group, respectively. An improvement of a least 2 NYHA Classes was achieved by 44% and 35% of patients in the original mavacamten group and crossover group, respectively.
  • There was a sustained reduction in resting LVOT gradient, Valsalva LVOT gradient, NT-proBNP, and troponin I in both groups. Moreover, sustained improvements in KCCQ score and in echo indices (LV mass index, LA volume index, E/e’) were seen
  • There were no differences in key efficacy findings between men and women.


  • 3 out of 108 patients (2.8%) permanently discontinued treatment with mavacamten.
  • 9 out of 108 patients (8.3%) had one temporary interruption for LVEF (>30% to <50%).
  • 12 out of 108 patients (11.1%) had LVEF of <50%. Of these patients, 9 (75%) were asymptomatic and able to resume mavacamten at lower dose after temporary interruption.


At week 56, mavacamten significantly lowered the incidence of the principal composite SRT endpoint in patients with oHCM. Sustained improvements in LVOT gradient, biomarkers and echo indices were seen after mavacamten treatment. However, continued monitoring is required given the potential for (asymptomatic) LV systolic dysfunction. “[Treatment with mavacamten] definitely provides an alternative for medically refractory patients with obstructive HCM, which may obviate the need for SRT in many patients. We however still continue to need long term studies of efficacy and outcomes”, says Milind Desai.

- Our reporting is based on the information provided at the ESC Congress 2023 –

The results of this study were simultaneously published in JAMA Cardiology

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