A66-22 Hemodynamic and Biomarker Improvements With Sotatercept in Pulmonary Arterial Hypertension: A Meta-Analysis of Randomized Controlled Trials

Background Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary pressures and right-heart failure. Sotatercept, a first-in-class activin signaling inhibitor, has shown encouraging results in improving pulmonary vascular remodeling and right-ventricular load. However, its hemodynamic effects have not been fully defined. Methods A systematic meta-analysis of randomized controlled trials evaluating sotatercept versus placebo in adults with PAH was conducted through October 2025. Four randomized controlled trials that reported hemodynamic parameter changes were included. The outcomes of the analysis were mean pulmonary arterial pressure (mPAP), right atrial pressure (RAP), cardiac output (CO), pulmonary vascular resistance (PVR), and NT-proBNP levels. Results Analysis was done on 921 patients (483 sotatercept, 438 placebo). Mean pulmonary arterial pressure (MD = −11.09 mm Hg; 95% CI − 20.16 to − 2.03; p = 0.02) and right atrial pressure (MD = −2.58 mm Hg; 95% CI − 3.29 to − 1.88; p < 0.00001) were both significantly reduced by sotatercept treatment. Cardiac output increased (MD = +0.30 L/min; 95% CI 0.28 to 0.32; p < 0.00001), while pulmonary vascular resistance significantly decreased (MD = −239.0 dyn·s·cm-5; 95% CI − 306.02 to − 171.98; p < 0.00001). Improved right-ventricular strain was also confirmed by a significant mean decrease in NT-proBNP levels (MD = −1240.55 pg/mL; 95% CI − 2135.7 to − 345.4; p = 0.007). Conclusion In patients with pulmonary arterial hypertension, sotatercept improves important hemodynamic parameters, resulting in reduced right-atrial and pulmonary pressures, decreased vascular resistance, increased cardiac output, and a concomitant drop in NT-proBNP. Further long-term studies are warranted to evaluate its sustained hemodynamic and survival benefits. This abstract is funded by: No funding source