Abstract Rationale Pulmonary arterial hypertension (PAH) remains a progressive and life-threatening disease characterized by elevated pulmonary vascular resistance, right-ventricular failure, and high morbidity and mortality despite advances in targeted therapies. Sotatercept, an activin signaling inhibitor, has emerged as a potential disease-modifying therapy. This meta-analysis synthesizes the most updated evidence evaluating the impact of sotatercept on mortality, functional capacity, hemodynamics, biomarkers, and safety in PAH. Methods This meta-analysis followed Cochrane and PRISMA guidelines. A systematic literature search was conducted in PubMed, Scopus, and the Cochrane Library to identify randomized controlled trials (RCTs) evaluating the efficacy of sotatercept in PAH, covering publications up to october 2025.Two independent reviewers screened the 538 initially identified records, assessing titles and abstracts for eligibility. Full-text articles meeting the inclusion criteria were subsequently reviewed. Any discrepancies were resolved by consensus or by consulting a third reviewer. Heterogeneity among studies was assessed using I² statistics. Results Four RCTs involving 921 participants were analyzed. Sotatercept significantly improved 6-minutes walking distance (6MWD) test (mean difference MD +30.81 m; 95% CI 15.27-46.35; p = 0.0001) and was associated to an improvement of World Health Organization (WHO) functional class (odds ratio OR 2.39; 95% CI 1.77-3.23; p 0.00001). Hemodynamic benefits included substantial reduction in pulmonary vascular resistance (PVR) (MD − 201.65 dyn·s·cm-5; 95% CI − 209.84 to − 193.46; p 0.00001) and NT-proBNP values (MD − 672.34 pg/mL; 95% CI − 1062.67 to − 282.00; p = 0.0007). A nonsignificant trend toward lower all-cause mortality was observed (risk ratio RR 0.63; 95% CI 0.35-1.14; p = 0.13). Severe adverse events occurred less frequently with sotatercept (OR 0.70; 95% CI 0.51-0.96; p = 0.03), indicating a favorable safety profile. Conclusion Sotatercept significantly improves functional capacity and hemodynamic parameters in PAH, with meaningful reductions in pulmonary vascular resistance, NT-proBNP and a favorable safety profile, without evidence of increased severe adverse events. While a mortality benefit was not statistically demonstrated, consistent improvements across key clinical outcomes support sotatercept as a promising disease-modifying therapy in PAH and reinforce its role in contemporary treatment strategies. Continued long-term data are needed to clarify survival benefit and durability of response. This abstract is funded by: None
Lúcio et al. (Fri,) studied this question.