Key result
Treprostinil reduces all-cause mortality ~34% vs. placebo in pulmonary arterial hypertension.
Why the study?
Despite numerous prostacyclin therapies with diverse delivery methods available for pulmonary arterial hypertension, head-to-head studies comparing them remain scarce.
What is the comparative efficacy and safety of prostacyclin pathway therapies (treprostinil, iloprost, selexipag, epoprostenol, and beraprost) on mortality, functional capacity, hemodynamics, and clinical worsening in patients with pulmonary arterial hypertension?
Meta-Analysis (n=7,819)
Yes
What is the comparative efficacy and safety of prostacyclin pathway therapies (treprostinil, iloprost, selexipag, epoprostenol, and beraprost) on mortality, functional capacity, hemodynamics, and clinical worsening in patients with pulmonary arterial hypertension?
This network meta-analysis differentiates prostacyclin therapies in PAH, showing that treprostinil reduces mortality by 34%, epoprostenol maximizes functional and hemodynamic improvements, iloprost provides the greatest PVR reduction, and selexipag best prevents clinical worsening and hospitalizations.
Answers are grounded in this paper and cite their sources.
Supports treprostinil prioritization for PAH survival benefit; extends network ranking of prostacyclin therapies by endpoint.
Background: Pulmonary arterial hypertension (PAH) is a progressive, fatal cardiopulmonary disorder characterized by elevated pulmonary vascular resistance leading to right heart failure. Current treatment utilizes pathway-specific vasodilators, including numerous prostacyclin therapies with diverse delivery methods. Despite available options, head-to-head studies comparing these treatments remain scarce. Aim: This network meta-analysis seeks to systematically evaluate all prostacyclin-based PAH therapies to guide clinical decision-making regarding treatment selection. Results: Our NWM comprising 32 studies (N = 7,819) revealed 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). Conclusion: Our NMA demonstrates that prostacyclin pathway therapies offer benefits in PAH management. While epoprostenol exhibits superior improvements in hemodynamics and functional capacity, treprostinil reduces mortality by 34%, and selexipag excels in preventing clinical worsening and hospitalizations.
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Saleh et al. (2025) conducted a meta-analysis in Pulmonary arterial hypertension (n=7,819). Prostacyclin pathway analogues (treprostinil, iloprost, selexipag, epoprostenol, beraprost) vs. Placebo, conventional therapy, or other prostacyclin pathway analogues was evaluated on All-cause mortality (treprostinil vs placebo) (RR 0.66, 95% CI 0.49-0.90). Treprostinil reduced all-cause mortality by 34% compared to placebo in patients with pulmonary arterial hypertension.
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