Mavacamten for Treatment of Symptomatic Obstructive Hypertrophic Cardiomyopathy - EXPLORER-HCM

Contribution To Literature:

The EXPLORER-HCM trial showed that mavacamten was superior to placebo at improving exercise capacity and health status.

Description:

The goal of the trial was to evaluate mavacamten, a cardiac myosin inhibitor, compared with placebo among patients with hypertrophic obstructive cardiomyopathy.

Study Design

  • Randomized
  • Parallel
  • Double-blind
  • Placebo

Eligible patients were randomized to mavacamten 5 mg daily (n = 123) versus placebo (n = 128) for 30 weeks.

  • Total number of enrollees: 251
  • Duration of follow-up: 30 weeks
  • Mean patient age: 59 years
  • Percentage female: 46%
  • Percentage with diabetes: 5%

Inclusion criteria:

  • ≥18 years of age
  • Hypertrophic obstructive cardiomyopathy (left ventricular outflow tract [LVOT] gradient ≥50 mm Hg)
  • LV ejection fraction (LVEF) ≥55%
  • New York Heart Association (NYHA) class II-III symptoms

Exclusion criteria:

  • Syncope
  • Sustained ventricular tachycardia with exercise within 6 months

Principal Findings:

The primary outcome, ≥1.5 ml/kg/min increase in pVO2 with ≥1 NYHA class improvement or ≥3.0 ml/kg/min increase in pVO2 with no worsening of NYHA class at 30 weeks, occurred in 37% of the mavacamten group compared with 17% of the placebo group (p = 0.0005).

Secondary outcomes:

  • Post-exercise LVOT gradient change from baseline to week 30: -47 mm Hg in the mavacamten group vs. -10 mm Hg in the placebo group (p < 0.0001)
  • pVO2 change from baseline to week 30: 1.4 ml/kg/min in the mavacamten group vs. -0.1 ml/kg/min in the placebo group (p = 0.0006)

Cardiac magnetic resonance (CMR) substudy analysis:

  • Change in LV mass index: -17.4 g/m2 in the mavacamten group vs. -1.6 g/m2 in the placebo group (p < 0.0001)
  • Change in LVEF: -6.6% in the mavacamten group vs. -0.3% in the placebo group (p = 0.0025)

Kansas City Cardiomyopathy Questionnaire (KCCQ):

  • At 30 weeks, change in KCCQ-overall summary score: 14.9 for mavacamten vs. 5.4 for placebo (difference +9.1, p < 0.0001)

Interpretation:

Among patients with hypertrophic obstructive cardiomyopathy, mavacamten was superior to placebo. This medicine improved functional capacity and health status, as assessed by KCCQ. Mavacamten was well tolerated. Mavacamten was associated with a significant reduction in post-exercise LVOT gradient compared with placebo. CMR found that mavacamten was associated with favorable remodeling compared with placebo.

References:

Spertus JA, Fine JT, Elliott P, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet 2021;May 15:[Epub ahead of print].

Presented by Dr. John A. Spertus at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 15, 2021.

Saberi S, Cardim N, Yamani M, et al. Mavacamten Favorably Impacts Cardiac Structure in Obstructive Hypertrophic Cardiomyopathy: EXPLORER-HCM CMR Substudy Analysis. Circulation 2021;143:606-8.

Presented by Dr. Sara Saberi at the American Heart Association Virtual Scientific Sessions, November 15, 2020.

Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2020;396:759-69.

Presented by Dr. Iacopo Olivotto at the European Society of Cardiology Virtual Congress, August 29, 2020.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, SCD/Ventricular Arrhythmias, Acute Heart Failure, Magnetic Resonance Imaging

Keywords: ACC21, ACC Annual Scientific Session, AHA20, AHA Annual Scientific Sessions, ESC Congress, ESC20, Cardiac Myosins, Cardiomyopathy, Hypertrophic, Exercise Tolerance, Heart Failure, Magnetic Resonance Imaging, Syncope, Stroke Volume, Tachycardia, Ventricular, Ventricular Function, Left


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