Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo, Brazil.
University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Eur Respir J. 2023 Sep 21;62(3). doi: 10.1183/13993003.01107-2023. Print 2023 Sep.
In the phase 3 STELLAR trial, sotatercept, an investigational first-in-class activin signalling inhibitor, demonstrated beneficial effects on 6-min walk distance and additional efficacy endpoints in pre-treated participants with pulmonary arterial hypertension (PAH).
This analysis evaluated data from right heart catheterisation (RHC) and echocardiography (ECHO) obtained from the STELLAR trial. Changes from baseline in RHC and ECHO parameters were assessed at 24 weeks. An analysis of covariance (ANCOVA) model was used to estimate differences in least squares means with treatment and randomisation stratification (mono/double triple therapy; World Health Organization functional class II III) as fixed factors, and baseline value as covariate.
Relative to placebo, treatment with sotatercept led to significant (all p<0.0001 except where noted) improvements from baseline in mean pulmonary artery (PA) pressure (-13.9 mmHg), pulmonary vascular resistance (-254.8 dyn·s·cm), mean right atrial pressure (-2.7 mmHg), mixed venous oxygen saturation (3.84%), PA elastance (-0.42 mmHg·mL·beat), PA compliance (0.58 mL·mmHg), cardiac efficiency (0.48 mL·beat·mmHg), right ventricular (RV) work (-0.85 g·m) and RV power (-32.70 mmHg·L·min). ECHO showed improvements in tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure ratio (0.12 mm·mmHg), end-systolic and end-diastolic RV areas (-4.39 cm and -5.31 cm, respectively), tricuspid regurgitation and RV fractional area change (2.04% p<0.050). No significant between-group changes from baseline were seen for TAPSE, heart rate, cardiac output, stroke volume or their indices.
In pre-treated patients with PAH, sotatercept demonstrated substantial improvements in PA pressures, PA compliance, PA-RV coupling and right heart function.
在 3 期 STELLAR 试验中，索塔来塞特（一种研究性的新型激活素信号抑制剂）在接受过治疗的肺动脉高压（PAH）患者中，在 6 分钟步行距离和其他疗效终点方面显示出有益的效果。
本分析评估了来自 STELLAR 试验的右心导管检查（RHC）和超声心动图（ECHO）的数据。在 24 周时评估 RHC 和 ECHO 参数相对于基线的变化。采用协方差分析（ANCOVA）模型，以治疗和随机分组（单/双/三重治疗；世界卫生组织功能分类 II/III）为固定因素，以基线值为协变量，估计最小二乘均数的差异。
与安慰剂相比，索塔来塞特治疗可显著改善平均肺动脉（PA）压（-13.9mmHg）、肺动脉阻力（-254.8dyn·s·cm）、平均右心房压（-2.7mmHg）、混合静脉血氧饱和度（3.84%）、PA 僵硬度（-0.42mmHg·mL·beat）、PA 顺应性（0.58mL·mmHg）、心效率（0.48mL·beat·mmHg）、右心室（RV）做功（-0.85g·m）和 RV 功率（-32.70mmHg·L·min），所有差异均有统计学意义（均 p<0.0001，除有注明外）。ECHO 显示三尖瓣环平面收缩期位移（TAPSE）与收缩期肺动脉压比值（0.12mm·mmHg）、收缩末期和舒张末期 RV 面积（分别为-4.39cm 和-5.31cm）、三尖瓣反流和 RV 分数面积变化（2.04%，p<0.050）的改善。TAPSE、心率、心输出量、每搏量及其指数在组间无显著的基线变化。
在接受过治疗的 PAH 患者中，索塔来塞特可显著改善 PA 压、PA 顺应性、PA-RV 耦联和右心功能。
