Key result
Cardiac myosin inhibitors improve exercise capacity by ~1.3 mL/kg/min and reduce LVOT gradients in HCM.
Why the study?
The comparative effectiveness, phenotype-specific effects, and safety profiles of the cardiac myosin inhibitors mavacamten and aficamten in hypertrophic cardiomyopathy are inconsistently reported.
Do cardiac myosin inhibitors (mavacamten and aficamten) improve peak VO2, LVOT gradients, and symptoms in patients with obstructive and non-obstructive hypertrophic cardiomyopathy?
Meta-Analysis (n=1,581)
Do cardiac myosin inhibitors (mavacamten and aficamten) improve peak VO2, LVOT gradients, and symptoms in patients with obstructive and non-obstructive hypertrophic cardiomyopathy?
This meta-analysis of 8 RCTs demonstrates that cardiac myosin inhibitors significantly improve exercise capacity, LVOT gradients, and symptoms predominantly in obstructive HCM without increasing serious adverse events.
Answers are grounded in this paper and cite their sources.
Supports use in symptomatic obstructive HCM to boost exercise capacity; confirms pooled RCT benefits without excess serious adverse events.
Background: Cardiac myosin inhibitors (CMIs), mavacamten and aficamten, directly regulate sarcomeric hypercontractility in hypertrophic cardiomyopathy (HCM). However, their comparative effectiveness, phenotype-specific effects, and safety profiles are inconsistently reported. Objectives: To assess the efficacy and safety of CMIs and analyze predefined subgroups based on drug (mavacamten vs. aficamten) and phenotype (obstructive vs. non-obstructive HCM). Methods: A systematic review and meta-analysis of randomized controlled trials was conducted following PRISMA guidelines. PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception to September 19, 2025. Data were pooled using random-effects models for continuous and binary outcomes, and certainty was graded using GRADE. Eight RCTs enrolling 1,581 participants were included. Results: CMIs significantly improved the primary efficacy outcomes: peak VO 2 (MD 1.25 mL/kg/min, 95% CI 0.43-2.07) and reduced both resting LVOT gradient (MD -57.27 mmHg [-63.05 to -51.49]) and post-Valsalva LVOT gradient (MD -53.00 mmHg [-61.99 to -44.01]), with benefits predominantly in obstructive HCM. For secondary outcomes, CMIs improved symptoms (KCCQ-CSS: MD 6.42 [3.99-8.86]; NYHA improvement: OR 2.50 [2.03-3.09]) and reduced NT-proBNP and troponin I levels, albeit with inter-study variability. Aficamten produced greater gains in peak VO 2 and NYHA class, whereas mavacamten showed stronger gradient reduction; subgroup differences were not definitive. Adverse events were slightly more frequent with CMIs (OR 1.35, p = 0.02), mainly with mavacamten, but serious events were not increased (RR 1.09, p = 0.55). Conclusions: CMIs significantly enhance hemodynamic and symptomatic outcomes, with maximal benefit in obstructive HCM and an acceptable safety profile. Comparative and long-term trials are warranted.
No takes yet. Share an insight, caveat, or question.
Khan et al. (2026) conducted a meta-analysis in Obstructive and non-obstructive hypertrophic cardiomyopathy (n=1,581). Cardiac myosin inhibitors (mavacamten and aficamten) was evaluated on Peak VO2, resting LVOT gradient, and post-Valsalva LVOT gradient (MD 1.25, 95% CI 0.43-2.07). Cardiac myosin inhibitors improved exercise capacity and reduced resting LVOT gradient in HCM.
Synapse has enriched 10 related papers. Consider them for comparative context: