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Clinical Trial
. 2025 Apr;44(4):609-624.
doi: 10.1016/j.healun.2024.11.037. Epub 2024 Dec 5.

Efficacy and safety of sotatercept across ranges of cardiac index in patients with pulmonary arterial hypertension: A pooled analysis of PULSAR and STELLAR

Mardi Gomberg-Maitland  1 , David B Badesch  2 , J Simon R Gibbs  3 , Ekkehard Grünig  4 , Marius M Hoeper  5 , Marc Humbert  6 , Grzegorz Kopeć  7 , Vallerie V McLaughlin  8 , Gisela Meyer  9 , Karen M Olsson  5 , Ioana R Preston  10 , Stephan Rosenkranz  11 , Rogerio Souza  12 , Aaron B Waxman  13 , Loïc Perchenet  14 , James Strait  14 , Aiwen Xing  14 , Amy O Johnson-Levonas  14 , Alexandra G Cornell  14 , Janethe de Oliveira Pena  14 , H Ardeschir Ghofrani  15
Affiliations
Clinical Trial

Efficacy and safety of sotatercept across ranges of cardiac index in patients with pulmonary arterial hypertension: A pooled analysis of PULSAR and STELLAR

Mardi Gomberg-Maitland et al. J Heart Lung Transplant. 2025 Apr.

Abstract

Background: This analysis examined the effects of the activin signaling inhibitor, sotatercept, in pulmonary arterial hypertension (PAH) subgroups stratified by baseline cardiac index (CI).

Methods: Pooled data from PULSAR (N = 106; NCT03496207) and STELLAR (N = 323; NCT04576988) were analyzed using 2 different CI thresholds, <2.0 and ≥2.0 liter/min/m2 as well as <2.5 and ≥2.5 liter/min/m2. Median changes from baseline at week 24 were evaluated using Hodges-Lehmann estimator and least squares (LS) means, with 95% confidence intervals and p-values (significance: p = 0.05). Categorial endpoints and time-to-clinical worsening were analyzed by Cochran-Mantel-Haenszel and Cox model respectively.

Results: Of 429 participants, 51 had CI <2.0 and 378 ≥2.0 liter/min/m2, while 179 had CI <2.5 and 250 ≥2.5 liter/min/m2. Sotatercept significantly improved median 6-minute walk distance (range: 33.9 to 63.7 m: p < 0.001), pulmonary vascular resistance (range: -202.8 to -395.4 dyn•s•cm-5; p ≤ 0.002), and N-terminal pro-B-type natriuretic peptide (range: -317.3 to -1,041.2 pg/ml; p < 0.001) across subgroups. LS means showed reductions in pulmonary and right atrial pressures, decreased right ventricular size, and improved tricuspid annular plane systolic excursion/systolic pulmonary artery pressure. Sotatercept delayed time to first occurrence of death or a worsening event for CI ≥2.5 (hazard ratio [HR] 0.12; p < 0.001), ≥2.0 (HR 0.13; p < 0.001), and <2.5 (HR 0.21; p < 0.001) liter/min/m2. Improvements were observed in WHO functional class (all p < 0.050) and ESC/ERS risk scores (all p < 0.001).

Conclusions: Sotatercept demonstrated consistent efficacy and safety across CI subgroups, supporting its use in PAH patients irrespective of baseline cardiac hemodynamics.

Keywords: cardiac index; cardiac output; hemodynamics; pulmonary arterial hypertension; sotatercept.

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