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).
Meta-Analysis (n=632)
Does mavacamten reduce LVOT gradients in adults with hypertrophic cardiomyopathy?
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.
Mean Difference: -38.28 (95% CI -45.92–-30.63)
p-value: p=<0.00001
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.
Khalil et al. (Wed,) 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).