Clinical Research
Pulmonary Vascular Disease
Safety and Efficacy of Inhaled Treprostinil as Add-On Therapy to Bosentan in Pulmonary Arterial Hypertension

https://doi.org/10.1016/j.jacc.2006.05.070Get rights and content
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Objectives

This study evaluated the safety and efficacy of inhaled treprostinil as add-on therapy to oral bosentan in patients with pulmonary arterial hypertension (PAH).

Background

The addition of a long-acting prostacyclin analogue via the inhaled route might be a safe and effective strategy to optimize therapy in PAH patients on bosentan.

Methods

Twelve patients with symptomatic PAH despite bosentan received either 30 μg of inhaled treprostinil 4 times daily (n = 6) or 45 μg 4 times daily (n = 6), via an ultrasonic nebulizer. Six-min walk distance (6MWD), functional class, and hemodynamics were assessed at baseline and 12 weeks.

Results

One patient was excluded from analysis due to the subsequent finding of pulmonary capillary hemangiomatosis. In the remaining 11 patients, inhaled treprostinil was safe and well tolerated. Inhaled treprostinil was associated with an increase in 6MWD at 12 weeks (baseline 339 ± 86, 12 week, 1 h post-inhalation 406 ± 121 m, 67-m change, p = 0.01). An improvement in 6MWD of 49 m from baseline was noted during the trough period, just before inhalation of treprostinil (p = 0.009). The 6MWD improvement of at least 10% was noted in 1 of 6 patients receiving 30 μg versus 5 of 6 receiving 45 μg. Over 12 weeks, significant decreases were noted in mean pulmonary arterial pressure (−10%) and in pulmonary vascular resistance (−26%). Functional class improved from III to II in 9 of 11 patients.

Conclusions

This trial suggests that inhaled treprostinil is safe, well tolerated, and associated with significant improvements in exercise capacity, functional class, and pulmonary hemodynamics in symptomatic patients with PAH on bosentan.

Abbreviations and Acronyms

ERA
endothelin receptor antagonist
PAH
pulmonary arterial hypertension
PAPmean
mean pulmonary arterial pressure
PCH
pulmonary capillary hemangiomatosis
PVR
pulmonary vascular resistance
6MWD
6-min walk distance

Cited by (0)

This research was partially funded by LungRx, Satellite Beach, Florida. Drs. Channick, Olschewski, and Seeger have received research funding from LungRx and have also received research funding and been consultants and speakers for Actelion Pharmaceuticals. Mr. Staub is an employee of LungRx. Dr. Rubin has been a consultant, speaker, and received research funding from Actelion Pharmaceuticals and has received research funding and been a consultant for LungRx. Robyn Barst, MD, served as guest editor for this manuscript.