Comparative Efficacy and Safety of Prostacyclin Therapies for Pulmonary Arterial Hypertension: A Systematic Review and Network Meta-Analysis

Khaled Saleh¹Jihad Mallat, MD, PhD^1*Samiuddin Mohammed¹Govinda Bodi¹Hosam Alazazzi²Simi Salim³Mohamed Elhennawi²Talha Iqbal⁴Hani Sabbour^5*

• ¹Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
• ²RCSI Bahrain, Adliya, Bahrain
• ³Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
• ⁴Medical School of Malaysia, Malaysia, Malaysia
• ⁵Mediclinic Hospitals and Clinics, Abu Dhabi, United Arab Emirates

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.We implemented a frequentist approach to network meta-analysis (NWM). For continuous outcomes, we calculated pooled mean differences (MD), whereas risk ratios (RR) were determined for binary endpoints. All estimates incorporated 95% confidence intervals. Results achieving p-values below 0.05 were considered statistically significant.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 (46.84m, 95%CI 21.90-71.78; P-score 0.90) versus placebo. Hemodynamically, epoprostenol achieved optimal Pulmonary Arterial Pressure (PAP) reduction (-6.29mmHg, 95%CI -6.99 to -5.59; P-score 0.95), while iloprost demonstrated superior Pulmonary Vascular Resistance (PVR) improvement ; P-score 1.00). Epoprostenol ranked highest for Right Atrial Pressure (RAP) reduction ) 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).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.