Long-term therapy with oral treprostinil in pulmonary arterial hypertension failed to lead to improvement in important physiologic measures: Results from a single center

Kelly Marie Chin, Rosechelle Ruggiero, Sonja Bartolome, Mariella Velez-Martinez, Konstantina Darsaklis, Martha Kingman, Scarlet Harden, Fernando Torres

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)513-520
Number of pages8
JournalPulmonary Circulation
Volume5
Issue number3
DOIs
StatePublished - 2015

Fingerprint

Pulmonary Hypertension
Hemodynamics
Vascular Resistance
Catheterization
Therapeutics
Epoprostenol
treprostinil
Oral Administration
Placebos

Keywords

  • Hemodynamics
  • Prostacyclin
  • Pulmonary arterial hypertension
  • Survival
  • Treatment

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Long-term therapy with oral treprostinil in pulmonary arterial hypertension failed to lead to improvement in important physiologic measures : Results from a single center. / Chin, Kelly Marie; Ruggiero, Rosechelle; Bartolome, Sonja; Velez-Martinez, Mariella; Darsaklis, Konstantina; Kingman, Martha; Harden, Scarlet; Torres, Fernando.

In: Pulmonary Circulation, Vol. 5, No. 3, 2015, p. 513-520.

Research output: Contribution to journalArticle

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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.",
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