Lee MMY; University of Glasgow, Glasgow, UK
Goldie FC; Henderson AD; Masri A; Olivotto I; Coats CJ

Progress in Cardiovascular Diseases. 94:16-26, 2026 Jan-Feb

AIMS: Data on cardiac myosin inhibitors (CMIs) in obstructive hypertrophic
cardiomyopathy (oHCM) are rapidly emerging. This systematic review and
meta-analysis evaluated the efficacy and safety of CMIs in randomized
placebo-controlled trials.

METHODS: Phase 3 randomized placebo-controlled trials published up to
22-Apr-2025 were included. Outcomes extracted included symptoms,
cardiopulmonary exercise testing (CPET), biomarkers, transthoracic
echocardiography (TTE), cardiovascular magnetic resonance (CMR), and
safety data. Frequentist (common/fixed effect, random) and Bayesian
meta-analyses were performed using trial-level data to pool estimates of
effects.

RESULTS: Four randomized placebo-controlled trials involving 726 patients
with oHCM were included (444 mavacamten/placebo, 282 aficamten/placebo).
Trial follow-up durations ranged from 16 to 30 weeks. In common/fixed
effects meta-analyses, CMIs were associated with a greater proportion
achieving >=1 NYHA improvement [difference 36 % (95 % CI 29, 43)] and an
increase in KCCQ-CSS [8.4 (6.6, 10.2) points] versus placebo. CMIs
significantly improved several CPET parameters including increased peak
oxygen consumption [1.6 (1.0, 2.1) mL/kg/min] and reduced VE/VCO2 [-2.0
(-2.7, -1.3)]. CMIs significantly reduced NT-proBNP [-79 % (-81 %, -77 %)]
and hs-cTnI [-50 % (-54 %, -46 %)]. CMIs led to significant reductions in
resting LVOT-G [-40 (-45, -35) mmHg] and favourable cardiac remodelling in
other TTE and CMR parameters. Although CMIs increased the likelihood of
LVEF <50 %, consistent with its known mechanism of action, none of these
patients developed heart failure. No significant differences were seen in
safety outcomes.

CONCLUSIONS: Mavacamten and aficamten significantly improve symptoms,
enhance exercise performance, improve cardiac biomarkers, reduce LVOT
obstruction, and promote favourable cardiac remodelling. These findings
suggest a class effect of CMIs.