efficacy and safety of sotatercept in pulmonary arterial hypertension: a systematic review

Context: pulmonary arterial hypertension (pah) is characterized by the narrowing and remodeling of small pulmonary arteries, resulting from an imbalance in signaling pathways that regulate cell proliferation. current therapeutic strategies for pah target specific pathways to enhance pulmonary hemodynamics, including soluble guanylate cyclase stimulators, endothelin receptor antagonists, and prostacyclin pathway modulators. sotatercept emerges as a promising therapeutic option that targets the underlying mechanism of pah by improving the integrity of the endothelial layer of pulmonary arteries, promoting cellular proliferation, and alleviating vascular dysfunction. objectives: this study systematically aims to review existing literature on the efficacy and safety of sotatercept in treating pah. methods: a comprehensive search was conducted across five online databases (pubmed, scopus, web of science, embase, and google scholar) to identify relevant studies. original studies with human participants that investigated the efficacy and safety of sotatercept in patients with pah were included. the primary outcomes assessed included clinical parameters such as pulmonary artery wedge pressure (pawp), pulmonary vascular resistance (pvr), mean right atrial pressure (mrap), mean pulmonary artery pressure (mpap), 6-minute walk distance (6mwd), and improvements in world health organization functional class (who fc) over follow-up periods of up to 24 weeks. additionally, adverse events such as thrombocytopenia, bleeding, headaches, telangiectasia, increased blood pressure, nausea, diarrhea, fatigue, and epistaxis were evaluated. results: after screening, nine studies involving a total of 323 participants were included in the review. the analysis revealed that sotatercept significantly reduced pvr and led to notable improvements in 6mwd and nt-probnp levels among patients. the treatment was well-tolerated across various dosages, with all evaluated adverse events being manageable. conclusions: the findings indicate that sotatercept is an effective therapeutic intervention for patients with pah, significantly reducing pvr while enhancing exercise capacity and improving biomarkers of heart failure. the adverse effects associated with sotatercept were generally mild and manageable. the results support the potential of sotatercept as a valuable addition to the current treatment landscape for pah. further studies are warranted to comprehensively evaluate all related outcomes and potential adverse events associated with this therapy.