Dramatic differences resulting from treatment timing of treprostinil in high-risk patients: a real-world data analysis

Abstract Background The role of prostacyclin is critical in pulmonary arterial hypertension (PAH) and parenteral prostacyclin is an essential treatment option for high-risk patients. However, its real-world utilization remains limited due to physician unfamiliarity and high costs. Comprehensive analysis of real-world treprostinil use has been scarce. Purpose This study aimed to investigate the treatment patterns and clinical response to treprostinil in real-world practice. Methods Patients prescribed treprostinil for PAH from 2011 to 2024 at two tertiary referral centers were identified. Clinical characteristics, treatment response and survival outcomes were analyzed. We categorized the study populations into three groups based on the timing of treprostinil initiation: optimal sequential combination therapy (when the patient reached intermediate to high risk), early triple combination (in high-risk patients), and delayed sequential combination therapy (delayed initiation of treprostinil in already diagnosed PAH when they reached the functional class IV or definite indication for lung transplantation). Results A total of 94 patients were identified, with 35 (37.2%) in optimal sequential combination therapy group, 12 (12.8%) in early triple combination therapy group, and 47 (50.0%) in delayed sequential combination therapy group. Hemodynamic characteristics and risk profiles for PAH were similar among the study groups except for functional class. The cumulative 1-year mortality rate in the overall population was 35.1%. 1-year mortality was significantly higher in delayed sequential combination therapy group (53.2%) compared to optimal sequential combination therapy group (20.0%) and early triple combination therapy group (8.3%) (p0.001). Optimal sequential combination and early triple combination therapy over delayed sequential combination therapy were identified as independent predictor for death at 1 year (adjusted HR 0.239, 95% CI 0.096-0.599, p=0.002; adjusted HR 0.107, 95% CI 0.014-0.811, p=0.031). The treatment response to treprostinil was significantly lower in the delayed sequential combination therapy group (40.4%) compared to the optimal sequential combination (85.7%) and early triple combination therapy group (75.0%) (p0.001). Optimal sequential combination and early triple combination therapy were associated with higher rates of successful transition to oral maintenance therapy (40.0% and 91.7%, respectively), whereas 8.5% of patients in the delayed sequential combination therapy group maintained therapy (p0.001). Conclusions Although the guideline recommends the optimal timing for intervention with parenteral prostacyclin, it is frequently delayed in real-world clinics. Treatment outcomes show dramatic differences based on the timing—early, optimal, and delayed. Furthermore, a transition to an oral IP3 receptor agonist was even possible for some patients who survived due to early intervention with parenteral prostacyclin.