Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial

Graphical abstract Summary of the main study findings. Treatment with sotatercept for 24 weeks significantly reduced right heart size and improved right ventricle (RV) function and haemodynamic status in patients with pulmonary arterial hypertension (PAH). Error bars in graphs represent standard error. ECHO: echocardiography; LVESA: left ventricle end-systolic area; mPAP: mean pulmonary artery pressure; mRAP: mean right atrial pressure; NT-proBNP: N-terminal pro-brain natriuretic peptide; PA: pulmonary artery; RVA-ED: right ventricular area in end-diastole; RVA-ES: right ventricular area in end-systole; RVESA: right ventricle end-systolic area; sPAP: systolic pulmonary artery pressure; TAPSE: tricuspid annular plane systolic excursion; TRG: tricuspid regurgitation gradient. Background 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). Methods This post hoc 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 versus triple therapy; World Health Organization functional class II versus III) as fixed factors, and baseline value as covariate. Results 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−5), mean right atrial pressure (−2.7 mmHg), mixed venous oxygen saturation (3.84%), PA elastance (−0.42 mmHg·mL−1·beat−1), PA compliance (0.58 mL·mmHg−1), cardiac efficiency (0.48 mL·beat−1·mmHg−1), right ventricular (RV) work (−0.85 g·m) and RV power (−32.70 mmHg·L·min−1). ECHO showed improvements in tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure ratio (0.12 mm·mmHg−1), end-systolic and end-diastolic RV areas (−4.39 cm2 and −5.31 cm2, 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. Conclusion In pre-treated patients with PAH, sotatercept demonstrated substantial improvements in PA pressures, PA compliance, PA–RV coupling and right heart function. Tweetable abstract In pre-treated patients with pulmonary arterial hypertension, the activin signalling inhibitor sotatercept improved haemodynamics and right heart function https://bit.ly/3KDue98