Abstract Background Pulmonary arterial hypertension (PAH) remains a challenging disorder despite advances in vasodilator-based therapies. Sotatercept, an activin signaling inhibitor, emerged as a new therapeutic agent that directly targets pulmonary vascular remodeling and right ventricular afterload. However, the overall effect of sotatercept on the major clinical outcomes has yet to be established. Methods A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched through October 2025 for randomized controlled trials evaluating sotatercept versus placebo in adults with PAH. Four major trials were included. The primary outcome was all-cause mortality. Secondary outcomes included change in six-minute walk distance (6MWD), PAH-related hospitalization or clinical worsening, improvement in WHO functional class, and safety outcomes such as serious adverse events. Results A total of 921 patients were included (sotatercept = 483; placebo = 438). Our analysis showed no statistically significant difference in the all-cause mortality (OR 0. 65 0. 34-1. 24; p = 0. 19) between the study groups. However, The Treatment group showed significant improvement in the functional capacity, with a pooled mean increase in 6MWD of + 30. 4 m 14. 2-46. 7; p = 0. 0002), and improved WHO functional class (OR 2. 39 1. 76-3. 23; p 0. 001). Moreover, sotatercept reduced the composite risk of PAH-related hospitalization or clinical worsening (OR 0. 17 0. 07-0. 4; p 0. 001). Serious Adverse-event rates were lower than the placebo group (OR 0. 72 0. 53₀. 99; p = 0. 04), confirming Sotatercept’s favorable safety profile Conclusion Our study highlights that among patients with PAH, the use of sotatercept did not reduce All-cause mortality. However, it demonstrated significant improvements in exercise capacity, functional class, and hospitalization risk, while maintaining an excellent safety profile. This abstract is funded by: No funding source was used
Akkawi et al. (Fri,) studied this question.
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