title: Inhaled iloprost for severe pulmonary hypertension.
abstract: BACKGROUND
  Uncontrolled studies suggested that aerosolized iloprost, a stable analogue of prostacyclin, causes selective pulmonary vasodilatation and improves hemodynamics and exercise capacity in patients with pulmonary hypertension.
  
  
  METHODS
  We compared repeated daily inhalations of 2.5 or 5.0 microg of iloprost (six or nine times per day; median inhaled dose, 30 microg per day) with inhalation of placebo. A total of 203 patients with selected forms of severe pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (New York Heart Association [NYHA] functional class III or IV) were included. The primary end point was met if, after week 12, the NYHA class and distance walked in six minutes were improved by at least one class and at least 10 percent, respectively, in the absence of clinical deterioration according to predefined criteria and death.
  
  
  RESULTS
  The combined clinical end point was met by 16.8 percent of the patients receiving iloprost, as compared with 4.9 percent of the patients receiving placebo (P=0.007). There were increases in the distance walked in six minutes of 36.4 m in the iloprost group as a whole (P=0.004) and of 58.8 m in the subgroup of patients with primary pulmonary hypertension. Overall, 4.0 percent of patients in the iloprost group (including one who died) and 13.7 percent of those in the placebo group (including four who died) did not complete the study (P=0.024); the most common reason for withdrawal was clinical deterioration. As compared with base-line values, hemodynamic values were significantly improved at 12 weeks when measured after iloprost inhalation (P<0.001), were largely unchanged when measured before iloprost inhalation, and were significantly worse in the placebo group. Further significant beneficial effects of iloprost treatment included an improvement in the NYHA class (P=0.03), dyspnea (P=0.015), and quality of life (P=0.026). Syncope occurred with similar frequency in the two groups but was more frequently rated as serious in the iloprost group, although this adverse effect was not associated with clinical deterioration.
  
  
  CONCLUSIONS
  Inhaled iloprost is an effective therapy for patients with severe pulmonary hypertension.
authors.affiliation: Department of Internal Medicine II, University Clinic, Giessen, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Olschewski
authors.forename: Gerald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galiè
authors.forename: Timothy
authors.initials: T
authors.lastname: Higenbottam
authors.forename: Robert
authors.initials: R
authors.lastname: Naeije
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
authors.forename: Sylvia
authors.initials: S
authors.lastname: Nikkho
authors.forename: Rudolf
authors.initials: R
authors.lastname: Speich
authors.forename: Marius M
authors.initials: MM
authors.lastname: Hoeper
authors.forename: Jürgen
authors.initials: J
authors.lastname: Behr
authors.forename: Jörg
authors.initials: J
authors.lastname: Winkler
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.forename: Wladimir
authors.initials: W
authors.lastname: Popov
authors.forename: H Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Manes
authors.forename: David G
authors.initials: DG
authors.lastname: Kiely
authors.forename: Ralph
authors.initials: R
authors.lastname: Ewert
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer
authors.forename: Paul A
authors.initials: PA
authors.lastname: Corris
authors.forename: Marion
authors.initials: M
authors.lastname: Delcroix
authors.forename: Miguel
authors.initials: M
authors.lastname: Gomez-Sanchez
authors.forename: Harald
authors.initials: H
authors.lastname: Siedentop
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
mesh_terms: D000280:Administration, Inhalation; D004417:Dyspnea / Q000188:drug therapy / Q000209:etiology; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000145:classification / Q000188:drug therapy* / Q000503:physiopathology; D016285:Iloprost / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016138:Walking
chemical_list: D014665:Vasodilator Agents; D016285:Iloprost