Comparative effectiveness of oral therapies targeting the prostacyclin pathway in pulmonary arterial hypertension. a systematic review and network meta-analysis

Background: Oral prostanoids are recommended in patients with pulmonary arterial hypertension (PAH) and a unsatisfactory response to first-line therapy. Objective: To compare effectiveness of oral therapies targeting the prostacyclin pathway in PAH patients. Methods: An online search of Medline, Cochrane Registry, Scopus and EMBASE libraries (from inception to May, 12020) was performed. Eight randomized controlled studies were included in the meta-analysis involving 3023 patients, of whom 828 receiving oral treprostinil, 607 patients receiving selexipag, 125 patients receiving beraprost, and 1463 patients received placebo. Results: As compared to placebo, oral treprostinil (WMD 9.05, 95% CI 3.0280-15.0839, p = 0.0032) and beraprost (WMD 21.98, 95% CI 5.0536-38.9063, p = 0.0109) arms significantly increased 6 min walking distance (6MWD) at follow-up from baseline, whereas selexipag use was associated with a non-significant increase in 6MWD (WMD 15.41, 95% CI -0.6074; 31.4232, p = 0.0593). Compared to placebo, the risk of clinical worsening was significantly lowered by selexipag (RR 0.47, 95% CI 0.35-0.65, p < 0.001) and oral treprostinil (RR 0.65, 95% CI 0.46-0.90, p 0.012), whereas a non-significant reduction of the outcome was related to beraprost use (RR 0.70, 95% CI 0.36-1.38, p 0.31). No significant difference in 6MWD change and clinical worsening reduction were found among oral treprostinil and selexipag. Beraprost use less frequently caused adverse events as compared to selexipag and oral treprostinil. Conclusions: No differences in 6MWD change, clinical worsening reduction and adverse events rates were found among oral treprostinil and selexipag, resulting in similar efficacy and safety profile.