Mavacamten for Treatment of Symptomatic Obstructive Hypertrophic Cardiomyopathy - EXPLORER-HCM
Contribution To Literature:
Highlighted text has been updated as of November 21, 2023.
The EXPLORER-HCM trial showed that mavacamten was superior to placebo at improving exercise capacity and health status.
The goal of the trial was to evaluate mavacamten, a cardiac myosin inhibitor, compared with placebo among patients with hypertrophic obstructive cardiomyopathy.
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%
- ≥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
- Sustained ventricular tachycardia with exercise within 6 months
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).
- 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)
Long-term extension study (n = 231, median 62 weeks):
- Treatment-emergent adverse events: 4.3%
- Change in resting LVOT gradient from baseline to 84 weeks: -32.8 mm Hg
- Change in Valsalva LVOT gradient from baseline to 84 weeks: -46.4 mm Hg
- Change in LVEF from baseline to 84 weeks: -9%
- Change in N-terminal pro–B-type natriuretic peptide from baseline to 84 weeks: -488 ng/L
Effects of mavacamten on measures of cardiopulmonary exercise testing:
- Mean change from baseline to 30 weeks in peak VE/VCO2: -1.9 with mavacamten vs. 0.5 with placebo (p < 0.001)
- Mean change from baseline to 30 weeks in peak METs: 0.4 with mavacamten vs. -0.02 with placebo (p < 0.001)
- Mean change from baseline to 30 weeks in peak circulatory power, mL/kg/min x mm Hg: 414.1 with mavacamten vs. -17.9 with placebo (p = 0.001)
Effects of mavacamten vs. placebo in women compared with men:
- Change in the primary outcome for women: 22%
- Change in the primary outcome for men: 19% (p for interaction = 0.76)
- Change in post-exercise LVOT gradient for women: -42.4 mm Hg
- Change in post-exercise LVOT gradient for men: -33.6 mm Hg (p for interaction = 0.35)
Among patients with hypertrophic obstructive cardiomyopathy, mavacamten was superior to placebo. This medicine improved functional capacity and health status, as assessed by KCCQ. Results were similar in women versus men. Mavacamten was well tolerated with no significant long-term treatment-related adverse events. Mavacamten was associated with a significant reduction in post-exercise LVOT gradient compared with placebo at 30 weeks, which was sustained to 48 weeks. CMR found that mavacamten was associated with favorable remodeling compared with placebo. Mavacamten also improved various measures of cardiopulmonary exercise testing.
Cresci S, Bach RG, Saberi S, et al. Effect of Mavacamten in Women Compared With Men With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM. Circulation 2023;Nov 14:[Epub ahead of print].
Wheeler MT, Olivotto I, Elliott PM, et al. Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial. JAMA Cardiol 2023;8:240-7.
Presented by Dr. Florian Rader at the American College of Cardiology Annual Scientific Session (ACC 2022), Washington, DC, April 3, 2022.
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;397:2467-75.
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.
Keywords: ACC22, ACC21, AHA20, ESC20, Cardiomyopathy, Hypertrophic, Exercise Tolerance, Heart Failure
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