Although oral treprostinil had been found to increase exercise capacity and postpone disease development in patients with pulmonary arterial hypertension (PAH), its effects on hemodynamics remained unknown. The FREEDOM-EV trial was a Phase III worldwide, placebo-controlled, double-blind, event-driven research including 690 PAH patients receiving a single oral PAH treatment. FREEDOM-EV indicated a considerably lower risk of clinical deterioration with oral treprostinil taken three times per day and did not reveal any new safety concerns in PAH patients. In addition, about 61 FREEDOM-EV trial participants agreed to participate in a hemodynamics sub-study. 

From baseline to Week 24, pulmonary artery compliance (PAC), a ratio of stroke volume to pulmonary pulse pressure, rose considerably in the oral treprostinil group compared to the placebo group (geometric mean 26.4% active vs. -6.0% placebo; ANCOVA P=0.007). In addition, from baseline to Week 24, the oral treprostinil group had a significant increase in cardiac output compared to the placebo group (geometric mean 11.3% active vs. -6.4% placebo; ANCOVA P=0.005) and a corresponding significant decrease in pulmonary vascular resistance (PVR) (geometric mean -21.5 active vs. -1.8% placebo; ANCOVA P=0.02). The findings showed that greater compliance contributed to the physiological mechanism by which oral treprostinil improved exercise capacity and postponed clinical deterioration in PAH patients.