title: Long-term therapy with oral treprostinil in pulmonary arterial hypertension failed to lead to improvement in important physiologic measures: results from a single center.
abstract: Sustained-release oral treprostinil, an oral prostacyclin, led to significant improvement in 6-minute walk distance (6MWD) versus placebo in treatment-naive patients with pulmonary arterial hypertension (PAH) but failed to lead to significant improvement in two 16-week trials in patients receiving background PAH therapies (FREEDOM studies). Long-term studies are lacking. Our objective was to evaluate 6MWD, functional class, hemodynamics, and other long-term outcomes during oral treprostinil administration in PAH. Patients receiving oral treprostinil through the FREEDOM studies at our institution were included and were followed for up to 7 years. The primary end point was change in pulmonary vascular resistance (PVR) at first follow-up catheterization. Other end points included 6MWD, functional class, and other hemodynamic results. Thirty-seven patients received oral treprostinil for a median of 948 days, with 81%, 61%, and 47% continuing therapy at 1, 2, and 3 years, respectively. Mean treprostinil dose at 3, 12, and 24 months was 4.3 ± 2.3, 8.6 ± 3.2, and 11.7 ± 5.8 mg/24 h, respectively. Compared with pretreatment values, there was no significant change in 6MWD at 3 or 12 months, no improvement in functional class at 12 months, and no significant change in hemodynamics at the first follow-up catheterization (N = 34). Oral treprostinil dose was inversely associated with change in PVR (r = -0.42, P < 0.05), and change in PVR was numerically better among patients in the highest dosing quartile. No significant improvement in 6MWD, functional class, or hemodynamics versus pretreatment values was seen with long-term oral treprostinil therapy, potentially because of inability to achieve a clinically effective dose.
authors.affiliation: Pulmonary and Critical Care Division, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Kelly Marie
authors.initials: KM
authors.lastname: Chin
authors.affiliation: Pulmonary and Critical Care Division, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Rosechelle
authors.initials: R
authors.lastname: Ruggiero
authors.affiliation: Pulmonary and Critical Care Division, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Sonja
authors.initials: S
authors.lastname: Bartolome
authors.affiliation: Cardiology Division, University of Maryland Medical Center, Baltimore, Maryland, USA.
authors.forename: Mariella
authors.initials: M
authors.lastname: Velez-Martinez
authors.affiliation: Pulmonary and Critical Care Division, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Darsaklis
authors.affiliation: Pulmonary and Critical Care Division, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Kingman
authors.affiliation: Pulmonary and Critical Care Division, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Scarlet
authors.initials: S
authors.lastname: Harden
authors.affiliation: Pulmonary and Critical Care Division, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Torres
keywords: hemodynamics; prostacyclin; pulmonary arterial hypertension; survival; treatment