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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, Sehnert, Amy J., Edelberg, Jay M., Li, Wanying, Olivotto, Iacopo·2023·European Journal of Heart Failure
DOI 10.1002/ejhf.2737
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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 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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CC-BY-NC-ND · From the PDF
Figure 1 Study profiles.
Figure 1 Study profiles.CC-BY-NC-ND · From the PDF
Figure 2 Mean (standard deviation [SD]) peak oxygen consumption (VO 2 ) ( A ), peak metabolic equivalents (METs) ( B ), peak exercise time ( C ), and peak heart rate ( D ) at baseline and week 30 in EXPLORER-HCM according to beta-blocker usage. CI, confidence interval.
Figure 2 Mean (standard deviation [SD]) peak oxygen consumption (VO 2 ) ( A ), peak metabolic equivalents (METs) ( B ), peak exercise time ( C ), and peak heart rate ( D ) at baseline and week 30 in EXPLORER-HCM according to beta-blocker usage. CI, confidence interval.CC-BY-NC-ND · From the PDF
Figure 3 Distribution of New York Heart Association (NYHA) functional class at week 30 in EXPLORER-HCM for mavacamten ( A ) and placebo ( B ) and at week 1 2 in the EXPLORER-LTE cohort of MAVA-LTE for mavacamten ( C ). a Patients who did not complete the week 1 2 visit at the cut-off date and patients who completed the week 1 2 visit at the cut-off date with missing NYHA functional class data at week 1 2 were excluded.
Figure 3 Distribution of New York Heart Association (NYHA) functional class at week 30 in EXPLORER-HCM for mavacamten ( A ) and placebo ( B ) and at week 1 2 in the EXPLORER-LTE cohort of MAVA-LTE for mavacamten ( C ). a Patients who did not complete the week 1 2 visit at the cut-off date and patients who completed the week 1 2 visit at the cut-off date with missing NYHA functional class data at week 1 2 were excluded.CC-BY-NC-ND · From the PDF

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Research works printed but not linked: 30

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Metadata

Authors
Wheeler, M. T., Jacoby, D., Elliott, P. M., Saberi, S., Hegde, S. M., Lakdawala, N. K., Myers, J., Sehnert, A. J., Edelberg, J. M., Li, W., & Olivotto, I.
Venue
European Journal of Heart Failure
Publisher
Oxford University Press (OUP)
Published
2023-02-01
Volume
25
Issue
2
Pages
260-270
ISSN
  • 1388-9842
  • 1879-0844
DOI
10.1002/ejhf.2737
Cited by
52
References
0
Language
en
Licence
Funders
  • MyoKardia, Inc.
  • MyoKardia

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