Mavacamten monotherapy in obstructive hypertrophic cardiomyopathy: an integrated analysis of phase 3 clinical trials

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: obstructive hypertrophic cardiomyopathy. Intervention: Mavacamten monotherapy vs. Mavacamten plus beta-blockers or calcium-channel blockers. Primary outcome: left ventricular outflow tract gradients and symptoms.

Q: What does this research mean for the field?

Mavacamten monotherapy improves left ventricular outflow tract gradients and symptoms in obstructive hypertrophic cardiomyopathy, showing efficacy and adverse event profiles comparable to combination therapy with beta-blockers or calcium-channel blockers. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Iacopo Olivotto; Pablo Garcia-Pavia; Zhuang Tian; Anjali Owens; Neal K. Lakdawala; Ganesh Balaratnam; Yue Zhong; Arteid Memaj; Yu Chen Barrett; Milind Desai

doi:10.1016/j.ahj.2026.107587

August 1, 2026American Heart JournalOpen Access

Mavacamten monotherapy in obstructive hypertrophic cardiomyopathy: an integrated analysis of phase 3 clinical trials

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Key result

Mavacamten monotherapy improves LVOT gradients and symptoms in obstructive HCM with LVEF reductions under ~9%.

Why the study?

Does mavacamten monotherapy improve left ventricular outflow tract gradients and symptoms in patients with obstructive hypertrophic cardiomyopathy?

Key Points

To evaluate the efficacy and safety of mavacamten administered as monotherapy compared to combination regimens in patients with obstructive hypertrophic cardiomyopathy.
Integrated analysis pooling data from four phase 3 clinical trials: EXPLORER-HCM, the EXPLORER cohort of MAVA-LTE, VALOR-HCM, and EXPLORER-CN.
Evaluated outcomes of mavacamten monotherapy compared descriptively to mavacamten administered with background beta-blockers or calcium-channel blockers over up to 128 weeks.
Mavacamten monotherapy was associated with improvements in left ventricular outflow tract gradients and clinical symptoms.
Descriptive comparisons between mavacamten monotherapy and mavacamten combined with beta-blockers or calcium-channel blockers demonstrated broadly similar trends in efficacy and adverse event rates.
Reductions in left ventricular ejection fraction from baseline through week 128 were ≤8.8% across all treatment groups.

Study Design

Type

Meta-Analysis

Structured PICO

Does mavacamten monotherapy improve left ventricular outflow tract gradients and symptoms in patients with obstructive hypertrophic cardiomyopathy?

P

Population

Patients with obstructive hypertrophic cardiomyopathy analyzed across four phase 3 clinical trials with follow-up to 128 weeks.

I

Intervention

Mavacamten monotherapy

C

Comparator

Mavacamten plus beta-blockers or calcium-channel blockers (descriptive comparison)

O

Outcome

Left ventricular outflow tract gradients and symptomssurrogate

Mavacamten monotherapy appears effective and safe for obstructive hypertrophic cardiomyopathy, showing similar efficacy and safety trends to combination therapy with beta-blockers or calcium-channel blockers.

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Implication

Mavacamten monotherapy may improve LVOT gradients and symptoms in obstructive HCM; leaves open comparative efficacy versus combination regimens.

Abstract

This study assessed mavacamten monotherapy efficacy and safety in an integrated analysis of four phase 3 studies: EXPLORER-HCM, the EXPLORER cohort of MAVA-LTE, VALOR-HCM and EXPLORER-CN. Mavacamten monotherapy was associated with improvements in left ventricular outflow tract gradients and symptoms in patients with obstructive hypertrophic cardiomyopathy; descriptive comparisons with patients receiving mavacamten plus beta-blockers or calcium-channel blockers suggested broadly similar trends in efficacy and adverse event rates. Reductions in left ventricular ejection fraction from baseline to week 128 of ≤8.8% were observed across treatment groups.

Discussion

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Cite This Study

Olivotto et al. (2026) conducted a meta-analysis in obstructive hypertrophic cardiomyopathy. Mavacamten monotherapy vs. Mavacamten plus beta-blockers or calcium-channel blockers was evaluated on left ventricular outflow tract gradients and symptoms. Mavacamten monotherapy improved left ventricular outflow tract gradients and symptoms in obstructive hypertrophic cardiomyopathy, with LVEF reductions of ≤8.8% at 128 weeks.

synapsesocial.com/papers/6aa9352015a756b5ce462917 https://doi.org/10.1016/j.ahj.2026.107587

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Mavacamten monotherapy in obstructive hypertrophic cardiomyopathy: an integrated analysis of phase 3 clinical trials

Key Points

Study Design

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Mavacamten monotherapy in obstructive hypertrophic cardiomyopathy: an integrated analysis of phase 3 clinical trials

Key Points

Study Design

Structured PICO

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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