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)

Interpretation:

Among patients with hypertrophic obstructive cardiomyopathy, mavacamten was superior to placebo. This medicine improved functional capacity and health status. 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:

Saberi S, Cardim N, Yamani M, et al. Mavacamten Favorably Impacts Cardiac Structure in Obstructive Hypertrophic Cardiomyopathy: EXPLORER-HCM CMR Substudy Analysis. Circulation 2020;Nov 15:[Epub ahead of print].

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, SCD/Ventricular Arrhythmias, Acute Heart Failure

Keywords: 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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