Clinical outcomes and safety of sotatercept in pulmonary arterial hypertension: A systematic review and meta-analysis of randomized controlled trials

Introduction

Pulmonary arterial hypertension (PAH) remains a life-threatening condition characterized by high morbidity and mortality. However, recent therapeutic advancements have offered a paradigm shift in terms of therapeutic goals.

Methods

We conducted a systematic review and meta-analysis of RCTs assessing clinical outcomes and safety of sotatercept when compared to placebo in PAH. Searches of Pubmed and Cochrane Central databases were performed through April 2025. The primary outcome was all-cause mortality. Secondary outcomes included improvements in 6MWD, WHO functional class, hemodynamics, NT-proBNP, and serious adverse events. Data were pooled using a random-effects model, with certainty of evidence assessed via GRADE methodology.

Results

Three RCTs comprising 601 patients were included. There was a non-significant trend toward reduced mortality (RR 0.49; 95 % CI 0.16 to 1.46; p = 0.11). Sotatercept was associated with significant improvements in 6MWD (MD 37.99 m; 95 % CI 6.47 to 69.52; p = 0.04) and WHO functional class (RR 2.04; 95 % CI 1.79 to 2.31; p = 0.002). Hemodynamic improvements included reductions in PVR (MD -237.73 dyn·s/cm⁵; 95 % CI -367.02 to −1.8.43; p = 0.02) and mPAP (MD -14.88 mmHg; 95 % CI -24.76 to −4.99; p = 0.02). Serious adverse events were similar (RR 0.79; 95 % CI 0.51 to 1.23; p = 0.15).

Conclusion

Sotatercept significantly improves functional and hemodynamic outcomes in PAH, with a favorable safety profile. While mortality benefits remain uncertain, these findings support its clinical utility as an emerging therapy in PAH.