Oral treprostinil 3 times a day (TID) improved pulmonary artery compliance (PAC) and cardiac output in patients with pulmonary arterial hypertension (PAH) on monotherapy and also reduced the risk of clinical worsening, according to results of a new study published in Respiratory Medicine.

FREEDOM-EV is a phase 3, international, placebo-controlled, double-blind, event-driven study on patients with PAH on oral treprostinil vs a control group taking a placebo. Over a 24-week period, PAC, a ratio of stroke volume to pulmonary pulse pressure, increased in a group of patients in FREEDOM-EV.

In addition to the improvement in PAC, cardiac output increased and there was a corresponding decline in pulmonary vascular resistance in the patients on treprostinil.

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“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,” the researchers wrote. “These data can be explained by the known pulmonary vasodilator effect of prostacyclin therapies.”

Read more about PAH experimental therapies

Sixty-one patients in FREEDOM-EV participated in this substudy on treprostinil and underwent 2 right heart catheterizations, 1 at baseline and 1 within 72 hours of the week 24 assessments. Thirty-four patients in the substudy took treprostinil and 27 took the placebo.

The median oral doses of treprostinil were higher in this patient group than in patients in the parent FREEDOM-EV trial (5.5 mg TID vs 3.6 mg TID); however, adverse events were similar in both groups, suggesting no additional safety issues resulted from the increased doses.

The improvements in PAC and cardiac output, in addition to the antiplatelet and anti-inflammatory properties of oral treprostinil, may have led to the significant delay to disease progression among patients with PAH in the parent FREEDOM-EV trial.


Khan A, White RJ, Meyer G et al. Oral treprostinil improves pulmonary vascular compliance in pulmonary arterial hypertension. Respir Med. Published online January 24, 2022. doi:10.1016/j.rmed.2022.106744