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

IF 6.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of Heart and Lung Transplantation Pub Date : 2024-12-05 DOI:10.1016/j.healun.2024.11.037

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.

查看原文本刊更多论文

索特西普在肺动脉高压患者心脏指数范围内的疗效和安全性：PULSAR和STELLAR的合并分析。

背景：本分析比较了激活素信号抑制剂索特西普在按基线心脏指数（CI）分层的肺动脉高压（PAH）亚组中的作用。方法：汇总PULSAR数据(N=106；NCT03496207)和STELLAR (N=323；NCT04576988)采用<和≥2.0 L/min/m2或2.5 L/min/m2两种不同的CI阈值进行分析。第24周与基线的变化中位数差异采用霍奇-莱曼（HL）估计量评估，均值差异采用最小二乘（LS）评估，置信区间和p值为95%；P =0.05差异有统计学意义。分类终点和临床恶化时间分别采用Cochran-Mantel-Haenszel模型和Cox模型（风险比（HR））进行分析，不进行多重校正。结果：在429名参与者中，51名和378名分别具有CI 2和≥2.0 L/min/m2，而179名和250名分别具有CI 2和≥2.5 L/min/m2。在所有CI亚组中，sotaterept与安慰剂相比显着改善了中位6分钟步行距离(范围：33.9至63.7 m: p-5；p≤0.002)，n端前b型利钠肽(范围：-317.3 ~ -1041.2 pg/mL；p2。结论：在基线CI亚组中，疗效和安全性是一致的，支持在PAH患者中使用索特西普，而不管基线心脏血流动力学如何。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Heart and Lung Transplantation 医学-呼吸系统

CiteScore

10.10

自引率

6.70%

发文量

1667

审稿时长

69 days

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.