A network meta-analysis conducted by researchers at the Cleveland Clinic Abu Dhabi, published in the October 2025 edition of Frontiers in Medicine, compared the efficacy and safety of prostacyclin therapies for pulmonary arterial hypertension (PAH) by synthesizing data from 32 studies, comprising 24 randomised controlled trials, three open-label trials,
and five cohort studies, with a cumulative sample size of 7,819 patients involving 7,819 patients.
The studies had follow-up periods ranging from one to 48 months. Five prostacyclin analogues were evaluated:
- treprostinil (n = 16 studies)
- iloprost (n = 5)
- selexipag (n = 6)
- epoprostenol (n = 4)
- beraprost (n = 3).
Direct head-to-head clinical trials comparing different prostacyclin agents have been lacking, making this indirect comparison particularly valuable for clinical decision-making.
The results revealed distinct therapeutic profiles among agents:
🔹 Significant mortality reduction with treprostinil versus placebo (RR 0.66, 95%CI 0.49–0.90), while epoprostenol transitioned demonstrated superior survival benefit (P-score 0.78).
🔹 For functional capacity, epoprostenol exhibited the greatest 6-Minute Walking Distance (6MWD) improvement (46.84 m, 95%CI 21.90–71.78; P-score 0.90) versus placebo.
🔹 Hemodynamically, epoprostenol achieved optimal Pulmonary Arterial Pressure (PAP) reduction (−6.29 mmHg, 95%CI -6.99 to −5.59; P-score 0.95), while iloprost demonstrated superior Pulmonary Vascular Resistance (PVR) improvement (−342.09, 95%CI -410.30 to −273.87; P-score 1.00).
🔹 Epoprostenol ranked highest for Right Atrial Pressure (RAP) reduction (−2.41 mmHg, 95%CI -2.65 to −2.18) and cardiac index improvement (0.56, 95%CI 0.49–0.63).
🔹 Regarding clinical worsening, selexipag showed potential superiority (RR 0.62, 95%CI 0.51–0.74; P-score 0.95) compared to treprostinil (P-score 0.55).
These findings suggest that treatment selection should be individualized based on specific therapeutic goals, patient risk profiles, and tolerability considerations, though the lack of direct comparative trials remains a significant limitation in the evidence base.
Citation
Saleh KM, Mallat J, Mohammed S, Bodi G, Alazazzi H, Salim S, Elhennawi M, Iqbal T and
Sabbour H (2025) Comparative efficacy and safety of prostacyclin therapies for pulmonary
arterial hypertension: a systematic review and network meta-analysis. Front. Med. 12:1643220. doi: 10.3389/fmed.2025.1643220
Read more at this link on Frontiers in Medicine