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Effect of beta-blocker therapy on the response to mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy

Wheeler, Matthew T; Jacoby, Daniel; Elliott, Perry M; Saberi, Sara; Hegde, Sheila M; Lakdawala, Neal K; Myers, Jonathan; ... Olivotto, Iacopo; + view all (2023) Effect of beta-blocker therapy on the response to mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy. European Journal of Heart Failure , 25 (2) pp. 260-270. 10.1002/ejhf.2737. Green open access

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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 NT-proBNP. Mavacamten benefits were reproduced and maintained in MAVA-LTE regardless of beta-blockade. CONCLUSION: Mavacamten improved measures of functional capacity, LVOT 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. This article is protected by copyright. All rights reserved.

Type: Article
Title: Effect of beta-blocker therapy on the response to mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/ejhf.2737
Publisher version: https://doi.org/10.1002/ejhf.2737
Language: English
Additional information: © 2022 MyoKardia, Inc and The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Keywords: Beta-blockers, Exercise capacity, Mavacamten, Obstructive hypertrophic cardiomyopathy, Symptoms
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science
URI: https://discovery.ucl.ac.uk/id/eprint/10160851
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