Efficacy and Safety of Mavacamten and Aficamten in Obstructive and Non-obstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis.

Ibrahim M., Kashif A., Arfin S. M. W., Mubeen M., Zafar A., Balach R., ...More

Critical Pathways in Cardiology, vol.Publish Ahead of Print, 2026 (Scopus) identifier identifier

  • Publication Type: Article / Review
  • Volume: Publish Ahead of Print
  • Publication Date: 2026
  • Doi Number: 10.1097/hpc.0000000000000418
  • Journal Name: Critical Pathways in Cardiology
  • Journal Indexes: Scopus, CINAHL, EMBASE, MEDLINE
  • Keywords: Aficamten, Cardiac myosin inhibitors, Hypertrophic cardiomyopathy, Left ventricular outflow tract gradient, Mavacamten, Meta-analysis, Randomized controlled trials
  • Azerbaijan State University of Economics (UNEC) Affiliated: No

Abstract

Cardiac myosin inhibitors (CMIs) are novel, disease-modifying therapies for hypertrophic cardiomyopathy (HCM). This meta-analysis evaluates the efficacy of CMIs versus placebo in patients with HCM. A systematic review and meta-analysis of randomized controlled trials (RCTs) involving adults with obstructive and non-obstructive HCM was performed following the PRISMA 2020 guidelines and registered on PROSPERO. Database including PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched through September 2025. Random-effects models were performed using SMDs for biomarker and WMDs for echocardiographic parameters. RRs were calculated for dichotomous outcomes, with 95% confidence intervals. Seven RCTs, comprising 1, 406 patients (732 CMI; 674 placebo) were included. CMIs significantly improved resting (WMD: −57.27 mmHg [−63.05, −51.49]; p < 0.001) and post-Valsalva LVOT gradient (WMD: −55.87 mmHg [−63.05, −51.49]; p < 0.001). LVEF decreased modestly (WMD: −4.74% [−7.22, −2.26]; p = 0.0002). CMIs increased the likelihood of ≥1 NYHA class improvement (RR: 1.94 [1.37, 2.74]; p < 0.001) and KCCQ-CSS (WMD: +6.60 points [3.84, 9.35]; p < 0.001). NT-proBNP (WMD: -13.35 [-18.04, -8.67]; p < 0.001) and cardiac troponin I (WMD: -11.90 [-15.07, -8.73]; p < 0.001) declined. Peak oxygen uptake showed no overall change (WMD: +0.64 mL/kg/min [−0.18, 1.47]; p = 0.12). CMIs increased adverse events (RR: 1.07 [1.02, 1.13]; p = 0.008), particularly hypertension (RR: 2.19 [1.06, 4.53]; p = 0.03). CMIs improve hemodynamics, functional status, and biomarkers in HCM with an acceptable safety profile and hold promise as disease-modifying therapy, though long-term outcomes require confirmation.