Key result
Mavacamten reduces post-exercise LVOT gradients by ~38 mmHg vs placebo in HCM.
Why the study?
Mavacamten targets the underlying mechanisms of hypertrophic cardiomyopathy, which often causes LVOT obstruction, heart failure, and sudden cardiac death.
Does mavacamten reduce LVOT gradients in adults with hypertrophic cardiomyopathy?
Meta-Analysis (n=632)
Does mavacamten reduce LVOT gradients in adults with hypertrophic cardiomyopathy?
Mean Difference: -38.28 (95% CI -45.92–-30.63)
p-value: p=<0.00001
Mavacamten effectively reduces LVOT gradients and NT-proBNP levels in patients with hypertrophic cardiomyopathy without increasing serious adverse events, though its impact on exercise capacity remains uncertain.
Mavacamten reduces post-exercise LVOT gradient in HCM; confirms hemodynamic benefit across six RCTs.
Background: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy, often leading to left ventricular outflow tract (LVOT) obstruction, heart failure, and sudden cardiac death. Mavacamten, a novel cardiac myosin inhibitor, targets the underlying mechanisms of HCM. Methods: We searched PubMed, Cochrane Library, and ClinicalTrials.gov up to 1 August 2025 and included six randomized controlled trials comparing Mavacamten to placebo in adults with HCM. The primary outcome was the change in LVOT gradients (post-exercise, post-Valsalva, and resting). Secondary outcomes included N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, left ventricular ejection fraction, peak oxygen consumption (pVO 2 ), and serious adverse events (SAEs). Data were analyzed using a random-effects model, with results reported as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). Meta-regression explored study-level moderators, and retrospective trial sequential analysis assessed the robustness of the findings. Results: Among 632 patients, Mavacamten significantly reduced LVOT gradients: post-exercise (MD: −38.28 mmHg, 95% CI: −45.92 to −30.63, P < 0.00001), post-Valsalva (MD: −59.02 mmHg, 95% CI: −82.75 to −35.29, P < 0.00001), and resting (MD: −44.50 mmHg, 95% CI: −66.49 to −22.51, P < 0.0001). NT-proBNP levels decreased significantly (MD: −617.26 ng/L, 95% CI: −772.43 to −462.09, P < 0.00001), but pVO 2 showed no significant change (MD: 0.69 mL/kg/min, 95% CI: −1.12 to 2.50, P = 0.45). SAEs were comparable (RR: 1.17, 95% CI: 0.58–2.36, P = 0.66). Across primary outcomes, retrospective trial sequential analysis confirms that Mavacamten’s reductions in LVOT gradients are conclusive, indicating robust evidence. Conclusion: Mavacamten effectively reduces LVOT gradients and NT-proBNP levels in HCM, but its impact on exercise capacity remains uncertain, with no increased risk of SAEs.
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Khalil et al. (2026) conducted a meta-analysis in Hypertrophic cardiomyopathy (n=632). Mavacamten vs. Placebo was evaluated on Change in LVOT gradients (post-exercise, post-Valsalva, and resting) (MD -38.28 mmHg, 95% CI -45.92 to -30.63, p=<0.00001). Mavacamten significantly reduced post-exercise LVOT gradients compared to placebo in adults with hypertrophic cardiomyopathy (MD -38.28 mmHg; 95% CI -45.92 to -30.63; P<0.00001).
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