Sotatercept significantly reduced clinical worsening or death by 77% (HR 0.23; 95% CI 0.16-0.32; p<0.001) compared to control in patients with pulmonary arterial hypertension.
Meta-Analysis (n=889)
Does sotatercept added to background therapy reduce clinical worsening or death in patients with pulmonary arterial hypertension?
Sotatercept as an add-on therapy significantly reduces clinical worsening or death and improves hemodynamics and functional class in patients with PAH, though it increases the risk of bleeding events.
Hazard Ratio: 0.23 (95% CI 0.16–0.32)
p-value: p=<0.001
Background: Pulmonary arterial hypertension (PAH) remains progressive despite contemporary background therapy. Sotatercept is a novel activin signaling inhibitor that targets pulmonary vascular remodeling and may improve clinical and hemodynamic outcomes. Objectives: To evaluate the efficacy, hemodynamic effects, and safety of sotatercept in patients with PAH. Design: Systematic review and meta-analysis of randomized controlled trials (RCTs). Data sources and methods: Five electronic databases were searched through October 2, 2025, for eligible RCTs. Time-to-event outcomes were analyzed using pooled individual patient data with hazard ratios (HRs), while secondary outcomes were assessed using random-effects risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CI). Trial-sequential analysis (TSA) evaluated the conclusiveness of results. Results: In four RCTs ( n = 889), sotatercept reduced clinical worsening or death by 77% (HR 0.23, 95% CI 0.16–0.32, p < 0.001) and prolonged event-free survival by ~40 weeks. World Health Organization (WHO) functional class improved in 40.3% vs 24.3% (RR 1.71, 95% CI 1.32–2.21), and 6-minute walk distance increased by MD 30.27 m (95% CI 13.45–47.08), while pulmonary vascular resistance (PVR) declined significantly (MD −247 dyn·s·cm– 5 , 95% CI −301.7; −192.2). Serious adverse events were slightly less frequent with sotatercept (26.2% vs 31.7%, RR 0.83); however, total bleeding (37.9% vs 18.7%, RR 2.00), epistaxis (26.7% vs 5.4%, RR 4.89), and telangiectasia (19.8% vs 6.4%, RR 3.24) were more common. TSA revealed conclusiveness in clinical worsening, WHO functional class, and PVR, as well as increases in bleeding events and epistaxis. Conclusion: Sotatercept significantly improves clinical outcomes and extends event-free survival in PAH, with an acceptable safety profile; however, caution is warranted regarding bleeding events. These results support its role as an add-on therapy in PAH management. Trial registration: PROSPERO ID: CRD420251166414.
Murad et al. (Mon,) conducted a meta-analysis in Pulmonary arterial hypertension (n=889). Sotatercept vs. control was evaluated on clinical worsening or death (HR 0.23, 95% CI 0.16-0.32, p=<0.001). Sotatercept significantly reduced clinical worsening or death by 77% (HR 0.23; 95% CI 0.16-0.32; p<0.001) compared to control in patients with pulmonary arterial hypertension.