Key result
Mavacamten improves oHCM functional capacity regardless of beta-blockers, though concurrent use blunts peak VO2 gains.
Why the study?
In EXPLORER-HCM, mavacamten effects on peak VO2 and NYHA class were greater without background beta-blockers, prompting investigation into whether background treatment effects were consistent across other clinically meaningful parameters.
Does mavacamten improve functional capacity, LVOT obstruction, and symptoms in patients with symptomatic obstructive hypertrophic cardiomyopathy regardless of background beta-blocker use?
RCT (n=251)
Does mavacamten improve functional capacity, LVOT obstruction, and symptoms in patients with symptomatic obstructive hypertrophic cardiomyopathy regardless of background beta-blocker use?
Mavacamten provides consistent benefits in reducing LVOT obstruction, symptom burden, and biomarkers in obstructive HCM regardless of background beta-blocker therapy, although beta-blocker-induced chronotropic incompetence attenuates peak VO2 improvements.
Answers are grounded in this paper and cite their sources.
Mavacamten-associated functional gains in oHCM persist with beta-blockers; hypothesis-generating for attenuated peak VO2 effects.
Aims In the EXPLORER-HCM trial, mavacamten improved exercise capacity and symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten effects on the primary endpoint, a composite of peak oxygen consumption (VO2) and New York Heart Association (NYHA) class, were greater in patients not receiving background beta-blockers than in those receiving beta-blockers. We sought to determine if the effect of background treatment was consistent across other clinically meaningful parameters. Methods and results Subgroup analyses by beta-blocker use were performed in patients with oHCM from the EXPLORER-HCM and mavacamten long-term extension (MAVA-LTE) studies. In EXPLORER-HCM, 189 patients (75.3%) were receiving beta-blockers, and 62 (24.7%) were receiving non-dihydropyridine calcium channel blockers or no background HCM medication; 170 patients (90.4%) receiving beta-blockers had chronotropic incompetence. Improvements in peak VO2 at week 30 with mavacamten versus placebo were lower with beta-blockers (mean difference [95% confidence interval (CI)]: 1.04 [0.12, 1.95] ml/kg/min) than without beta-blockers (mean difference [95% CI]: 2.69 [1.29, 4.09] ml/kg/min); improvements in non-heart rate-dependent parameters (VE/VCO2 slope) appeared unaffected by beta-blockers. Improvements in functional capacity parameters at week 30 with mavacamten versus placebo were independent of beta-blockade for post-exercise left ventricular outflow tract gradient (mean difference [95% CI]: −37.9 [−48.0, −27.9] mmHg with beta-blockers; −33.5 [−53.6, −13.3] mmHg without beta-blockers), proportion of patients with reduction of ≥1 NYHA class, Kansas City Cardiomyopathy Questionnaire clinical summary scores and N-terminal pro-B-type natriuretic peptide. Mavacamten benefits were reproduced and maintained in MAVA-LTE regardless of beta-blockade. Conclusion Mavacamten improved measures of functional capacity, left ventricular outflow tract obstruction, symptom burden and biomarkers in patients with HCM regardless of beta-blocker use. Beta-blocker use was often associated with chronotropic incompetence, affecting peak VO2 and other heart rate-dependent measures, but had minimal impact on heart rate-independent measures.
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Wheeler et al. (2022) conducted an RCT in symptomatic obstructive hypertrophic cardiomyopathy (oHCM) (n=251). Mavacamten vs. Placebo was evaluated on Improvement in peak VO2 at week 30 in patients receiving beta-blockers (mean difference 1.04 ml/kg/min, 95% CI 0.12-1.95). Mavacamten improved functional capacity in oHCM regardless of beta-blocker use, though peak VO2 improvement versus placebo was lower with beta-blockers (mean difference 1.04 vs 2.69 ml/kg/min).
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