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).
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.
Effect estimate: mean difference 1.04 ml/kg/min (95% CI 0.12-1.95)
Abstract 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.
Wheeler et al. (Sun,) conducted a 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).