Inhaled iloprost for severe pulmonary hypertension

被引:1266
作者
Olschewski, H
Simonneau, G
Galiè, N
Higenbottam, T
Naeije, R
Rubin, LJ
Nikkho, S
Speich, R
Hoeper, MM
Behr, J
Winkler, J
Sitbon, O
Popov, W
Ghofrani, HA
Manes, A
Kiely, DG
Ewert, R
Siedentop, H
Seeger, W
机构
[1] Univ Clin, Dept Internal Med 2, D-35392 Giessen, Germany
[2] Hop Antoine Beclere, Serv Pneumol, Clamart, France
[3] Univ Bologna, Ist Cardiol, Bologna, Italy
[4] Royal Hallamshire Hosp, Sheffield S10 2JF, S Yorkshire, England
[5] Erasme Univ Hosp, Dept Cardiol, B-1070 Brussels, Belgium
[6] Univ Calif San Diego, Med Ctr, La Jolla, CA 92093 USA
[7] Schering, Berlin, Germany
[8] Univ Hosp, Dept Internal Med, Zurich, Switzerland
[9] Hannover Med Sch, Dept Pneumol, D-3000 Hannover, Germany
[10] Univ Munich Grosshadern, Div Pulm Dis, Munich, Germany
[11] Univ Clin, Dept Pneumol, Leipzig, Germany
[12] Ernst Moritz Arndt Univ Greifswald, Dept Pneumol & Infect Dis, Greisswald, Germany
[13] Univ Hamburg, Klinikum Eppendorf, Bereich Pneumol, Med Kerklin & Poliklin, Hamburg, Germany
[14] Freeman Rd Hosp, Newcastle Upon Tyne, Tyne & Wear, England
[15] Gasthuisberg Univ Clin, Dept Pneumol, Louvain, Belgium
[16] Hosp 12 Octubre, Pulm Hypertens Unit, E-28041 Madrid, Spain
关键词
D O I
10.1056/NEJMoa020204
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mug of iloprost (six or nine times per day; median inhaled dose, 30 mug 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.
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页码:322 / 329
页数:8
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