Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension.
BACKGROUND
Small, open-label studies suggest that combinations of existing therapies may be effective for pulmonary arterial hypertension (PAH).


OBJECTIVE
To evaluate the safety and efficacy of adding inhaled iloprost, a prostacyclin analog, to the endothelin receptor antagonist bosentan in patients with PAH.


METHODS
In a randomized, multicenter, double-blind trial, inhaled iloprost (5 mug) or placebo was added to stable monotherapy with bosentan for 12 wk. Efficacy endpoints included change from baseline in 6-min-walk distance (6-MWD), modified New York Heart Association (NYHA) functional class, hemodynamic parameters, and time to clinical worsening.


RESULTS
A total of 67 patients with PAH (55% idiopathic PAH, 45% associated PAH, 94% NYHA class III, and mean baseline 6-MWD of 335 m) were randomized. At Week 12, patients receiving iloprost had a mean increase in 6-MWD of 30 m (p = 0.001); placebo patients had a mean 6-MWD increase of 4 m (p = 0.69), with a placebo-adjusted difference of +26 m (p = 0.051). NYHA status improved by one class in 34% of iloprost versus 6% of placebo patients (p = 0.002). Iloprost delayed the time to clinical worsening (p = 0.0219). Improvements were noted in postinhalation placebo-adjusted change in mean pulmonary artery pressure (-8 mm Hg; p < 0.001) and pulmonary vascular resistance (-254 dyn x s x cm(-5); p < 0.001). Combination therapy was well tolerated.


CONCLUSIONS
Within the limitations of a relatively small sample size, results of this study demonstrate that the addition of inhaled iloprost in patients with PAH with reduced exercise capacity on bosentan monotherapy is safe and efficacious.
McLaughlin
Vallerie V
VV
The University of Michigan Health System, Ann Arbor, Michigan, USA. vmclaugh@umich.edu
Oudiz
Ronald J
RJ
Frost
Adaani
A
Tapson
Victor F
VF
Murali
Srinivas
S
Channick
Richard N
RN
Badesch
David B
DB
Barst
Robyn J
RJ
Hsu
Henry H
HH
Rubin
Lewis J
LJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000077300:Bosentan; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D016285:Iloprost / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013449:Sulfonamides / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D013449:Sulfonamides; D014665:Vasodilator Agents; D016285:Iloprost; D000077300:Bosentan