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

Vascul Pharmacol. 2024 Mar:154:107280. doi: 10.1016/j.vph.2024.107280. Epub 2024 Feb 1.

Abstract

Background: Oral prostanoids are recommended in patients with pulmonary arterial hypertension (PAH) and an unsatisfactory response to first-line therapy.

Objective: To compare the 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, 12,020) was conducted. Eight randomized controlled studies were included in the meta-analysis involving 3023 patients, with 828 receiving oral treprostinil, 607 patients receiving selexipag, 125 patients receiving beraprost, and 1463 patients receiving placebo.

Results: 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) were associated with a significant increase in 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 profiles.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Acetamides
  • Antihypertensive Agents* / therapeutic use
  • Epoprostenol / therapeutic use
  • Humans
  • Hypertension, Pulmonary* / diagnosis
  • Hypertension, Pulmonary* / drug therapy
  • Network Meta-Analysis
  • Pulmonary Arterial Hypertension* / diagnosis
  • Pulmonary Arterial Hypertension* / drug therapy
  • Pyrazines

Substances

  • Acetamides
  • Antihypertensive Agents
  • Epoprostenol
  • Pyrazines
  • selexipag