EXPLORER-HCM
Trial question
What is the role of mavacamten in patients with symptomatic obstructive HCM?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
41.0% female
59.0% male
N = 251
251 patients (102 female, 149 male).
Inclusion criteria: patients with HCM with LVOT gradient ≥ 50 mmHg and NYHA class II-III symptoms.
Key exclusion criteria: history of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months before screening; QT interval corrected using Fridericia's formula > 500 ms; paroxysmal or intermittent AF; and persistent or permanent AF not on anticoagulation for ≥ 4 weeks or not adequately rate-controlled within 6 months before screening.
Interventions
N=123 mavacamten (a starting dose of 5 mg for 30 weeks).
N=128 placebo (matching placebo for 30 weeks).
Primary outcome
Clinical response at week 30
37%
17%
37.0 %
27.8 %
18.5 %
9.3 %
0.0 %
Mavacamten
Placebo
Significant
increase ▲
NNT = 5
Significant increase in clinical response at week 30 (37% vs. 17%; AD 19.4%, 95% CI 8.7 to 30.1).
Secondary outcomes
Significantly greater improvement in peak oxygen consumption at week 30 (1.4 mL/kg/min vs. -0.1 mL/kg/min; AD 1.4 mL/kg/min, 95% CI 0.6 to 2.1).
Significant increase in ≥ 1 NYHA class improvement at week 30 (65% vs. 31%; AD 34%, 95% CI 22.2 to 45.4).
Safety outcomes
No significant difference in serious adverse events.
Conclusion
In patients with HCM with LVOT gradient ≥ 50 mmHg and NYHA class II-III symptoms, mavacamten was superior to placebo with respect to clinical response at week 30.
Reference
Iacopo Olivotto, Artur Oreziak, Roberto Barriales-Villa et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020 Sep 12;396(10253):759-769.
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