title: Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension.
abstract: 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.
authors.affiliation: The University of Michigan Health System, Ann Arbor, Michigan, USA. vmclaugh@umich.edu
authors.forename: Vallerie V
authors.initials: VV
authors.lastname: McLaughlin
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Oudiz
authors.forename: Adaani
authors.initials: A
authors.lastname: Frost
authors.forename: Victor F
authors.initials: VF
authors.lastname: Tapson
authors.forename: Srinivas
authors.initials: S
authors.lastname: Murali
authors.forename: Richard N
authors.initials: RN
authors.lastname: Channick
authors.forename: David B
authors.initials: DB
authors.lastname: Badesch
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.forename: Henry H
authors.initials: HH
authors.lastname: Hsu
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
mesh_terms: 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*
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D014665:Vasodilator Agents; D016285:Iloprost; D000077300:Bosentan