Treprostinil significantly reduced mortality versus placebo (RR 0.66; 95% CI 0.49-0.90), while epoprostenol provided superior improvements in hemodynamics and functional capacity.
Meta-Analysis (n=7,819)
Do prostacyclin therapies improve mortality, functional capacity, hemodynamics, and clinical worsening in patients with pulmonary arterial hypertension?
Different prostacyclin therapies offer distinct benefits in PAH management, with treprostinil reducing mortality, epoprostenol optimizing hemodynamics and functional capacity, and selexipag preventing clinical worsening.
Effect estimate: RR 0.66 (95% CI 0.49-0.90)
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. Methods: -values below 0.05 were considered statistically significant. 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.
Saleh et al. (Mon,) conducted a meta-analysis in Pulmonary arterial hypertension (PAH) (n=7,819). Prostacyclin therapies (treprostinil, epoprostenol, iloprost, selexipag) vs. Placebo was evaluated on Mortality (RR 0.66, 95% CI 0.49-0.90). Treprostinil significantly reduced mortality versus placebo (RR 0.66; 95% CI 0.49-0.90), while epoprostenol provided superior improvements in hemodynamics and functional capacity.