Efficacy and safety of treprostinil in pulmonary arterial hypertension: a meta-analysis of randomized trials

Background Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disorder characterized by elevated pulmonary vascular resistance and mean pulmonary artery pressure. Treprostinil, a prostacyclin analog has vasodilatory and antiproliferative properties that may improve exercise capacity, hemodynamics and clinical outcomes in patients with PAH. Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing Treprostinil with placebo in PAH patients. Databases searched included PubMed, EMBASE, Scopus, Cochrane and from inception up to March 2025. Primary outcomes included change in 6-minute walk distance(6MWD), functional class, clinical worsening, mortality and adverse events. Pooled estimates were calculated using mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes, both with 95% confidence intervals (CI). All the analysis was conducted using Review Manager version 5.4 and the risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. Results Seven randomized controlled trials involving a total of 2447 patients were included with 1,288 receiving treprostinil and 1159 receiving placebo. The majority of participants (89.7%) were middle-aged females with a mean age of 48.85±0.96 years. Most had idiopathic or heritable pulmonary arterial hypertension (64%) and were primarily classified as WHO functional class II or III. Follow-up durations ranged from 16 to 60 weeks. Treprostinil significantly improved 6MWD compared to placebo (MD=15.47; 95%CI:10.01–20.92; p<0.00001; I2=20%) (Figure 1). Subgroup analysis showed benefit for both oral (MD=13.56; 95%CI:7.79–19.33; p<0.00001; I2=1%) and IV/subcutaneous (MD=19.89; 95%CI:6.73-33.05; p=0.003; I2=43%) administration routes. Treprostinil showed a non-significant trend toward improved functional class (RR=1.39; 95%CI: 0.92–1.95; p=0.06; I²=21%) and significantly reduced the risk of clinical worsening (RR=0.68; 95%CI:0.54–0.96; p=0.02; I²=9%). Mortality did not differ significantly (RR=1.24; 95%CI:0.89–1.88; p=0.23; I²=56%). Adverse events were more frequent with treprostinil (RR=1.13; 95%CI:1.01–1.77; p=0.002; I²=7%). Conclusion Treprostinil improves exercise capacity and reduces the risk of clinical worsening in patients with PAH, regardless of the route of administration. However, its use is associated with a higher incidence of adverse events which may affect treatment tolerability and adherence.