Key result
Sotatercept improves walking distance by ~31 meters vs placebo in PAH.
Why the study?
Pulmonary arterial hypertension remains a progressive and life-threatening disease despite advances in targeted therapies. This study evaluated the pooled efficacy and safety of sotatercept, an activin receptor type IIA ligand trap targeting pulmonary vascular remodeling, in patients with PAH.
Does sotatercept improve functional capacity, hemodynamic parameters, and safety outcomes compared with placebo in patients with pulmonary arterial hypertension?
Meta-Analysis (n=1,031)
Does sotatercept improve functional capacity, hemodynamic parameters, and safety outcomes compared with placebo in patients with pulmonary arterial hypertension?
Answers are grounded in this paper and cite their sources.
Pooled evidence from 5 RCTs confirms that sotatercept significantly improves exercise capacity, hemodynamics, and NT-proBNP in PAH patients, though monitoring for bleeding and hypertension is warranted.
Background: Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease despite advances in targeted therapies. Sotatercept, a first-in-class activin receptor type IIA ligand trap, targets pulmonary vascular remodeling and may provide a disease-modifying treatment approach. Research question: We aimed to evaluate the efficacy and safety of sotatercept in patients with PAH. Methods: A systematic review and meta-analysis of randomized controlled trials evaluating sotatercept in patients with PAH was conducted according to PRISMA guidelines. PubMed/MEDLINE, Cochrane Library, and Google Scholar were searched from inception through April 2026. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were pooled using random-effects models. Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Five randomized controlled trials comprising 1,031 patients were included. Compared with placebo, sotatercept significantly improved 6-minute walk distance (MD 30.77, 95% CI 15.19-46.36), WHO functional class improvement (RR 1.70, 95% CI 1.37-2.11), pulmonary vascular resistance (MD -237.46, 95% CI -292.55 to -182.38), mean pulmonary artery pressure (MD -14.85, 95% CI -19.57 to -10.14), NT-proBNP (MD -1134.11, 95% CI -2025.21 to -243.01), right atrial pressure (MD -2.58, 95% CI -3.30 to -1.86), and cardiac output (MD 0.24, 95% CI 0.06-0.42). No significant differences were observed in all-cause mortality, overall adverse events, or treatment discontinuation. However, sotatercept was associated with higher risks of bleeding events (RR 1.84, 95% CI 1.40-2.43) and hypertension (RR 3.34, 95% CI 1.35-8.25). Conclusion: Sotatercept significantly improves functional capacity, hemodynamic parameters, and biomarkers in patients with pulmonary hypertension while demonstrating an acceptable overall safety profile. Although bleeding events and hypertension were more frequent, sotatercept represents a promising adjunctive therapy for pulmonary arterial hypertension.
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Jialin et al. (2026) conducted a meta-analysis in Pulmonary arterial hypertension (PAH) (n=1,031). Sotatercept vs. Placebo was evaluated on 6-minute walk distance (MD 30.77, 95% CI 15.19-46.36). Sotatercept improved walking distance and PVR vs placebo in PAH.
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