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 MD, MSc , David B. Badesch MD , J. Simon R. Gibbs MD, FRCP , Ekkehard Grünig MD , Marius M. Hoeper MD , Marc Humbert MD, PhD , Grzegorz Kopeć MD, PhD , Vallerie V. McLaughlin MD, FACC, FAHA , Gisela Meyer MD , Karen M. Olsson MD , Ioana R. Preston MD , Stephan Rosenkranz MD , Rogerio Souza MD, PhD , Aaron B. Waxman MD, PhD , Loïc Perchenet PhD , James Strait MD, PhD , Aiwen Xing PhD , Amy O. Johnson-Levonas PhD , Alexandra G. Cornell MD, MCR , Janethe de Oliveira Pena MD, PhD , H. Ardeschir Ghofrani MD
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引用次数: 0
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.
期刊介绍:
The Journal of Heart and Lung Transplantation, the official publication of the International Society for Heart and Lung Transplantation, brings readers essential scholarly and timely information in the field of cardio-pulmonary transplantation, mechanical and biological support of the failing heart, advanced lung disease (including pulmonary vascular disease) and cell replacement therapy. Importantly, the journal also serves as a medium of communication of pre-clinical sciences in all these rapidly expanding areas.