Inhaled iloprost for severe pulmonary hypertension.
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.
Olschewski
Horst
H
Department of Internal Medicine II, University Clinic, Giessen, Germany.
Simonneau
Gerald
G
Galiè
Nazzareno
N
Higenbottam
Timothy
T
Naeije
Robert
R
Rubin
Lewis J
LJ
Nikkho
Sylvia
S
Speich
Rudolf
R
Hoeper
Marius M
MM
Behr
Jürgen
J
Winkler
Jörg
J
Sitbon
Olivier
O
Popov
Wladimir
W
Ghofrani
H Ardeschir
HA
Manes
Alessandra
A
Kiely
David G
DG
Ewert
Ralph
R
Meyer
Andreas
A
Corris
Paul A
PA
Delcroix
Marion
M
Gomez-Sanchez
Miguel
M
Siedentop
Harald
H
Seeger
Werner
W
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
D014665:Vasodilator Agents; D016285:Iloprost