Physicians' Academy for Cardiovascular Education

Effect of beta-blockade on improvements associated with cardiac myosin inhibitor in obstructive HCM

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

Literature - Wheeler MT, Jacoby D, Elliott PM, et al., - Eur J Heart Fail. 2022; doi:10.1002/ejhf.2737

Introduction and methods


Mavacamten is a selective inhibitor of cardiac myosin that reduces cardiac muscle contractility by inhibiting excessive myosin-actin cross-bridge formation [1,2]. In the EXPLORER-HCM trial, mavacamten improved exercise capacity and symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM) [3]. Mavacamten effects on the primary composite endpoint of peak oxygen consumption (VO2) and NYHA class were greater in patients not receiving background beta-blockers than in those receiving beta-blockers [3]. Beta-blockers may selectively affect the beneficial effects of mavacamten with regard to peak VO2 increase (heart-rate dependent), but not of other important, non-heart rate-dependent study endpoints.

Aim of the study

This post hoc analysis of data from EXPLORER-HCM and interim data from MAVA-LTE studied the effects of concomitant beta-blocker use on the response to mavacamten in patients with symptomatic oHCM.


The EXPLORER-HCM, a phase 3, double-blind, randomized, placebo-controlled, parallel group trial of mavacamten in patients with symptomatic oHCM enrolled a total of 251 adults with NYHA class II or III obstructive HCM with LVEF ≥55% and left ventricular outflow tract (LVOT) peak gradient ≥50 mmHg at baseline. Patients were randomized (1:1) to receive either mavacamten or placebo once daily for 30 weeks.

MAVA-LTE is an ongoing, 5-year study of mavacamten in patients who had completed either EXPLORER-HCM or the MAVERICK-HCM study [6]; 231 of 244 patients who completed EXPLORER-HCM enrolled in MAVA-LTE. All patients in MAVA-LTE received mavacamten irrespective of background HCM medication received in the original study. Patients and investigators were blinded to mavacamten dose and prior assigned treatment. In the present subgroup analyses only patients who enrolled into MAVA-LTE from the EXPLORER-HCM study, referred to as the EXPLORER-LTE cohort, were included.

In the EXPLORER-HCM, 189 patients (75.3%) received beta-blockers and 62 patients (24.7%) calcium channel blockers or no background medications. 224 patients were enrolled in the EXPLORER-LTE cohort of the MAVA-LTE study and received mavacamten. Overall, 169 patients (75.4%) were receiving concomitant beta-blockers; the remaining patients were prescribed calcium channel blockers (n=37) or neither background medication (n=18).


The main outcomes for this post-hoc analysis included change in peak VO2, peak metabolic equivalents (MET), peak heart rate, peak exercise time, ventilatory efficiency, LVOT gradient, LVEF, proportion of patients with a ≥1 class of NYHA improvement, change in KCCQ clinical summary score, and change in biomarkers. Analyses for EXPLORER-HCM were performed at week 30 and for the ongoing MAVA-LTE interim data from week 12 were used.

Main results

Functional capacity



Serum biomarkers


Results from both EXPLORER-HCM and EXPLORER-LTE showed that treatment with mavacampten improved measures of functional capacity, LVOT gradients, symptom burden and serum NT proBNP levels in patients with HCM regardless of beta-blocker use. Beta-blocker use was often linked to chronotropic incompetence, affecting peak VO2 and other heart rate-dependent measures, but had minimal impact on heart-rate independent measures.

The authors conclude: “The potential adverse effects of chronotropic incompetence related to beta-blocker use in oHCM requires critical reappraisal in clinical practice”.


Show references

Find this article online at Eur J Heart Fail.

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