Oral treprostinil improves pulmonary vascular compliance in pulmonary arterial hypertension

Akram Khan, R. James White, Gisela Meyer, Tomas R. Pulido Zamudio, Carlos Jerjes-Sanchez, Dana Johnson, Rob Grover, Meredith Broderick, Aliou Ousmanou, Louis Holdstock, Evangelos Michelakis

Research output: Contribution to journalArticlepeer-review

Abstract

Oral treprostinil has been shown to improve exercise capacity and delay disease progression in patients with pulmonary arterial hypertension (PAH), but its effects on hemodynamics are not well-characterized. The FREEDOM-EV trial was a Phase III, international, placebo-controlled, double-blind, event-driven study in 690 participants with PAH who were taking a single oral PAH therapy. FREEDOM-EV demonstrated a significantly reduced risk for clinical worsening with oral treprostinil taken three times daily and did not uncover new safety signals in PAH patients. Sixty-one participants in the FREEDOM-EV trial volunteered for a hemodynamics sub-study. Pulmonary artery compliance (PAC), a ratio of stroke volume to pulmonary pulse pressure, significantly increased from Baseline to Week 24 in the oral treprostinil group compared with the placebo group (geometric mean 26.4% active vs. -6.0% placebo; ANCOVA p=0.007). There was a significant increase in cardiac output in the oral treprostinil group compared to the placebo group (geometric mean 11.3% active vs. -6.4% placebo; ANCOVA p=0.005) and a corresponding significant reduction in pulmonary vascular resistance (PVR) (geometric mean -21.5 active vs. -1.8% placebo; ANCOVA p=0.02) from Baseline to Week 24. These data suggest that increased compliance contributes to the physiological mechanism by which oral treprostinil improves exercise capacity and delays clinical worsening for patients with PAH.

Original languageEnglish (US)
Article number106744
JournalRespiratory Medicine
Volume193
DOIs
StatePublished - Mar 2022
Externally publishedYes

Keywords

  • Cardiac output
  • FREEDOM-EV
  • Hemodynamics
  • PVR
  • Right-heart catherization

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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