Kumar G B; All India Institute of Medical Sciences, Bhubaneswar, India.
S M; Ibrahimpur NS; M R; Meher BR

European Journal of Clinical Pharmacology. 82(9), 2026 Aug 12.

BACKGROUND: Management of symptomatic non-obstructive hypertrophic
cardiomyopathy (HCM) remains challenging, and evidence comparing
pharmacological therapies is limited. While several randomized controlled
trials (RCTs) have evaluated individual agents, direct comparisons across
multiple therapies are lacking. This study aimed to compare the efficacy
of available pharmacological treatments for non-obstructive HCM using
network meta-analysis.

METHODS: This frequentist network meta-analysis was conducted following
PRISMA-NMA guidelines. Randomized controlled trials evaluating
pharmacological therapies in adult patients with non-obstructive HCM were
identified through systematic searches of major databases. Continuous
outcomes were analyzed using mean differences (MD) with 95% confidence
intervals (CI), while NT-proBNP was analyzed using the ratio of means
(RoM). The primary outcome was change in peak oxygen consumption (peak
VO2). Secondary outcomes included VE/VCO2 slope, NT-proBNP levels, E/e’
ratio, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and left
ventricular ejection fraction (LVEF).

RESULTS: Nine RCTs involving 1,057 patients were included. No
pharmacological therapy demonstrated a significant improvement in peak
VO2, the primary outcome. Mavacamten significantly reduced NT-proBNP
compared with placebo (RoM 0.42, 95% CI 0.32-0.56, I2 = 0%), whereas ARNI
and ninerafaxstat significantly improved VE/VCO2 slope, and candesartan
improved E/e’ ratio. No significant differences were observed for KCCQ
score or LVEF.

CONCLUSIONS: Different pharmacological therapies may provide benefits in
specific physiological domains in patients with non-obstructive HCM;
however, no single therapy demonstrated consistent improvements across all
evaluated outcomes. These findings highlight the heterogeneity of
treatment effects and suggest that targeting multiple pathophysiological
pathways may be important. Larger randomized and head-to-head comparative
studies are needed to define optimal management in this population.