Efficacy and Safety of Selexipag in Pulmonary Hypertension: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Selexipag, a selective prostacyclin receptor agonist, has been evaluated in randomized controlled trials (RCTs) for the treatment of pulmonary hypertension (PH), but results remain inconsistent. We performed an updated meta-analysis to assess its efficacy and safety. PubMed, Embase, and Cochrane databases were searched systematically from September 2025. Eligible studies were RCTs comparing selexipag with placebo in adults with PH. The primary outcome was the change in pulmonary vascular resistance (PVR). Secondary outcomes included 6-minute walk distance (6MWD), all-cause mortality, hospitalization for worsening PH, N-terminal pro-brain natriuretic peptide (NT-proBNP), serious adverse events (SAEs), and treatment-related adverse events (AEs). A random-effects meta-analysis was conducted using RevMan. Six RCTs enrolling 1686 patients were included. Selexipag therapy was associated with a statistically significant reduction in NT-proBNP (WMD = -150.19 pg/mL; 95% confidence interval [CI] -185.88 to -114.51), hospitalization for worsening PH (odds ratio [OR] = 0.63; 95% CI, 0.48-0.84), and SAEs (OR = 0.47; 95% CI, 0.38-0.59). Selexipag did not significantly reduce PVR (WMD = - 68.0 dyn·s·cm-5; 95% CI, -145.9 to 9.9) or improve 6MWD (WMD = -1.05 m; 95% CI, - 4.6 to 2.5), or mortality (OR = 0.80; 95% CI, 0.44-1.45) as compared with placebo. Selexipag reduces hospitalizations, SAEs, and NT-proBNP levels but shows no clear benefit on PVR or 6MWD. Future trials are needed to confirm these findings.