Safety and efficacy of inhaled treprostinil as add-on therapy to bosentan in pulmonary arterial hypertension.
OBJECTIVE
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 microg of inhaled treprostinil 4 times daily (n = 6) or 45 microg 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 microg versus 5 of 6 receiving 45 microg. 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.
Channick
Richard N
RN
UCSD Medical Center, La Jolla, California 92037, USA. rchannick@ucsd.edu
Olschewski
Horst
H
Seeger
Werner
W
Staub
Ted
T
Voswinckel
Robert
R
Rubin
Lewis J
LJ
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D011464:Epoprostenol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008168:Lung / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D013449:Sulfonamides; D011464:Epoprostenol; D000077300:Bosentan; C427248:treprostinil