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

Giovanna Manzi; Marco Valerio Mariani; Domenico Filomena; Silvia Papa; Tommaso Recchioni; Gianmarco Scoccia; Carmine Dario Vizza; Roberto Badagliacca

doi:10.1016/j.ijcard.2023.131691

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

Int J Cardiol. 2023 Dec 27:131691. doi: 10.1016/j.ijcard.2023.131691. Online ahead of print.

Authors

Giovanna Manzi¹, Marco Valerio Mariani¹, Domenico Filomena¹, Silvia Papa¹, Tommaso Recchioni¹, Gianmarco Scoccia¹, Carmine Dario Vizza², Roberto Badagliacca¹

Affiliations

¹ Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Policlinico Universitario Umberto I, Sapienza University of Rome, 00161 Rome, Italy.
² Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Policlinico Universitario Umberto I, Sapienza University of Rome, 00161 Rome, Italy. Electronic address: dario.vizza@uniroma1.it.

PMID: 38158135
DOI: 10.1016/j.ijcard.2023.131691

Abstract

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.

Keywords: Beraprost; Oral prostanoids; Oral treprostinil; Pulmonary arterial hypertension; Selexipag.