Inhaled Iloprost To Treat Severe Pulmonary Hypertension: An Uncontrolled Trial

  1. Horst Olschewski, MD;
  2. H. Ardeschir Ghofrani, MD;
  3. Thomas Schmehl, PhD;
  4. Jörg Winkler, MD;
  5. Heinrike Wilkens, MD;
  6. Marius M. Höper, MD;
  7. Jürgen Behr, MD;
  8. Franz-Xaver Kleber, MD;
  9. Werner Seeger, MD; and
  10. for the German PPH Study Group*
  1. From Justus-Liebig-University, Gieβen; University Clinic, Leipzig; University Clinics of Saarland, Homburg/Saar; Medical School, Hannover; University Clinic Groβhadern, Munich; and Accident Clinic, Berlin, Germany.

    Abstract

    Background: Inhaled aerosolized iloprost, a stable prostacyclin analogue, has been considered a selective pulmonary vasodilator in the management of pulmonary hypertension.

    Objective: To assess the efficacy of inhaled iloprost in the treatment of life-threatening pulmonary hypertension.

    Design: Open, uncontrolled, multicenter study.

    Setting: Intensive care units and pulmonary hypertension clinics at six university hospitals in Germany.

    Patients: 19 patients who had progressive right-heart failure despite receiving maximum conventional therapy (12 with primary pulmonary hypertension, 3 with pulmonary hypertension related to collagen vascular disease without lung fibrosis, and 4 with secondary pulmonary hypertension).

    Intervention: Inhaled iloprost, 6 to 12 times daily (50 to 200 µg/d).

    Measurements: Right-heart catheterization and distance walked in 6 minutes at baseline and after 3 months of therapy.

    Results: During the first 3 months of therapy, New York Heart Association functional class improved in 8 patients and was unchanged in 7 patients. Four patients died, 3 of right-heart failure and 1 of sepsis. The acute hemodynamic response to inhaled iloprost was predominant pulmonary vasodilatation with little systemic effect at baseline and at 3 months (data available for 12 patients). Hemodynamic variables were improved at 3 months, and the distance walked in 6 minutes improved by 148 m (95% CI, 4.5 to 282 m; P = 0.048). Of the 15 patients who continued to use inhaled iloprost, 8 stopped: Four had lung transplantation, 1 switched to intravenous prostacyclin therapy, and 3 died. Seven patients are still receiving inhaled iloprost [mean ±SD] duration of therapy, 536 ± 309 days; mean dosage, 164 ± 38 µg/d).

    Conclusions: Inhaled iloprost may offer a new therapeutic option for improvement of hemodynamics and physical function in patients with life-threatening pulmonary hypertension and progressive right-heart failure that is refractory to conventional therapy.

    *For additional members of the German PPH Study Group, see the Appendix.

    Article and Author Information

    • Acknowledgments: The authors thank Saskia Diehl and Friederike Rohlfing for data preparation and illustrations; Ralph Wiedemann and Xavier Lopes-Ribeiro for technical assistance; Wolfgang Pabst and Dr. R.H. Bödeker, Institute for Medical Statistics, Justus-Liebig-University Gieβen, for the statistics; and Mary Kay Steen-Mueller, MD, for carefully reviewing the manuscript.

    • Grant Support: By the PPH e.V., gemeinnütziger Selbsthilfe- und Förderverein, and Deutsche Forschungsgemeinschaft, SFB 547.

    • Requests for Single Reprints: Werner Seeger, MD, Department of Internal Medicine II, Justus-Liebig-University, Klinikstrasse 36, D-35392 Gieβen, Germany; e-mail, werner.seeger{at}innere.med.uni-giessen.de.

    • Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.

    • Current Author Addresses: Drs. Olschewski, Ghofrani, Schmehl, and Seeger: Department of Internal Medicine II, Justus-Liebig-University, Klinikstrasse 36, D-35392 Gieβen, Germany.

    • Dr. Winkler: Department of Pneumology, University Clinic, Johannesallee 32, D-04103 Leipzig, Germany.

    • Dr. Wilkens: Department of Pneumology, University Clinics of Saarland, Im Gelände, D-66421 Homburg/Saar, Germany.

    • Dr. Höper: Department of Pneumology, Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.

    • Dr. Behr: Department of Pneumology, University Clinic Groβhadern, Marchioninistrasse 15, D-81377 Munich, Germany.

    • Dr. Kleber: Department of Internal Medicine, Accident Clinic, Rapsweg 55, D-12683 Berlin, Germany.

    • Author Contributions: Conception and design: H. Olschewski, H.A. Ghofrani, W. Seeger.

    • Analysis and interpretation of the data: H. Olschewski, H.A. Ghofrani, T. Schmehl, M.M. Höper, F.-X. Kleber, W. Seeger.

    • Drafting of the article: H. Olschewski, W. Seeger.

    • Critical revision of the article for important intellectual content: H. Olschewski, H.A. Ghofrani, M.M. Höper, F.-X. Kleber.

    • Final approval of the article: H. Olschewski, H.A. Ghofrani, J. Winkler, H. Wilkens, M.M. Höper, J. Behr, W. Seeger.

    • Provision of study materials or patients: H. Olschewski, H.A. Ghofrani, J. Winkler, H. Wilkens, M.M. Höper, J. Behr, F.-X. Kleber, W. Seeger.

    • Statistical expertise: H. Olschewski, T. Schmehl.

    • Administrative, technical, or logistic support: T. Schmehl, J. Winkler, W. Seeger.

    • Collection and assembly of data: H. Olschewski, H.A. Ghofrani, T. Schmehl, J. Winkler, H. Wilkens, M.M. Höper, J. Behr, F.-X. Kleber.

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    1. Ann Intern Med March 21, 2000 vol. 132 no. 6 435-443
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