Comparative efficacy of pharmacological therapies in non-obstructive hypertrophic cardiomyopathy: a frequentist network meta-analysis.

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.