Sotatercept for pulmonary arterial hypertension on background therapy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND

Pulmonary arterial hypertension (PAH) is a progressive condition that leads to right ventricular failure and reduced survival. Sotatercept, a fusion protein targeting the activin signaling pathway, may offer disease-modifying benefits.

OBJECTIVE

This study aimed to evaluate the efficacy and safety of sotatercept compared to placebo in adults with PAH receiving background therapy.

METHODS

A systematic literature search was conducted through April 2025 to identify randomized controlled trials (RCTs) comparing sotatercept with placebo in PAH. Data were pooled using risk ratios (RR) or mean differences (MD) with 95% confidence intervals, analyzed using R software.

RESULTS

Three RCTs including 601 patients were analyzed. Sotatercept significantly improved 6-minute walk distance (MD: 38.4 m, P < 0.001), reduced NT-proBNP levels (MD: -852.85 pg/mL, P = 0.02), and lowered pulmonary vascular resistance (MD: -200.25 dyn·s·cm-5, P < 0.001). World Health Organization functional class improved (RR: 2.04, P < 0.001), and mortality, right ventricular failure, and treatment discontinuation decreased. Overall adverse events were similar between groups (RR: 1.01, P = 0.65), but class-related events such as bleeding and hematologic abnormalities were more frequent.

CONCLUSION

Sotatercept significantly improves clinical outcomes in PAH but requires close monitoring for bleeding and hematologic adverse events.