Early initiation and rapid escalation of parenteral treprostinil decreased mean pulmonary artery pressure by 23% (p<0.0001) and significantly improved PAH risk status at 12 months.
Does early initiation and rapid titration of high-dose treprostinil reduce mean pulmonary artery pressure and improve risk status in patients with pulmonary arterial hypertension?
Early initiation and rapid escalation of high-dose treprostinil significantly reduces mean pulmonary artery pressure and improves risk status in patients with pulmonary arterial hypertension.
valor p: p=<0.0001
Abstract Rationale Guidelines emphasize tailoring PAH therapy to risk assessment, but emerging evidence suggests that targeting right ventricular (RV) afterload reduction as a therapy goal may reverse disease progression. The ARTISAN study (NCT05203510) evaluates 1) initiation of parenteral treprostinil early in the treatment algorithm and 2) aggressive dose-titration as a strategy to reduce mean pulmonary artery pressure (mPAP) and enhance right ventricular function. Methods ARTISAN is a prospective, multicenter, open-label study of parenteral treprostinil initiated early and titrated rapidly to reach high treprostinil dose to reduce mPAP. At the baseline catheterization, a CardioMEMS™ HF System was implanted to facilitate remote weekly monitoring of mPAP. Participants were eligible to be transitioned, per investigator discretion, to oral treprostinil once mPAP fell consistently below 35 mmHg. REVEAL lite 2 risk score, cardiac MRI, clinical parameters, and EmPHasis-10 score were assessed at baseline and month 12. Data are reported as mean±standard deviation unless otherwise specified, with p-values calculated using standard statistical methods. Results This interim analysis includes 23 of 52 enrolled participants with completed 12-month measurements. Time from PAH diagnosis to treprostinil initiation was 3±2 months. Baseline mPAP was 53±12 mmHg, and REVEAL Lite 2 risk score was 7±3; 57% of patients were classified as high risk, and 65% classified as WHO FC III. Parenteral treprostinil dose was uptitrated to achieve 43±12 ng/kg/min at month 3, 61±21 ng/kg/min at month 6, and 84±27 ng/kg/min at month 9. At month 12, parenteral treprostinil dose was 93±27 ng/kg/min (n = 12) and oral treprostinil total daily dose was 25±9 mg (n = 11). From baseline to month 12, mPAP decreased by 23% (p 0.0001). REVEAL Lite 2 risk score decreased by 2±2 (p 0.0001), with 70% reaching low risk status and 87% at WHO FC II. Median (IQR) NT-proBNP decreased by -383.0 (-2366.0, 26.0) pg/mL (p 0.02). 6MWD increased by 32±58 meters (p 0.02), and quality of life EmPHasis-10 score improved by 9±12 (p = 0.001). Adverse events were consistent with the known safety profile of treprostinil. Of the 52 enrolled, 6 participants who were high-risk at screening or baseline died; none were related to study drug or study protocol. Conclusion Early initiation and rapid escalation to high-dose treprostinil therapy resulted in substantial reductions in RV afterload, along with significant improvements in PAH risk status, NT-proBNP, and quality of life EmPHasis-10 score after 12 months. This abstract is funded by: United Therapeutics Corporation
Benza et al. (Fri,) conducted a other in Pulmonary Arterial Hypertension (n=52). Parenteral treprostinil (with optional transition to oral) was evaluated on Mean pulmonary artery pressure (mPAP) reduction (p=<0.0001). Early initiation and rapid escalation of parenteral treprostinil decreased mean pulmonary artery pressure by 23% (p<0.0001) and significantly improved PAH risk status at 12 months.