Published ahead of print on August 31, 2006, doi:10.1164/rccm.200603-358OC
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 1257-1263, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200603-358OC
Randomized Study of Adding Inhaled Iloprost to Existing Bosentan in Pulmonary Arterial Hypertension
Vallerie V. McLaughlin,
Ronald J. Oudiz,
Adaani Frost,
Victor F. Tapson,
Srinivas Murali,
Richard N. Channick,
David B. Badesch,
Robyn J. Barst,
Henry H. Hsu and
Lewis J. Rubin
The University of Michigan Health System, Ann Arbor, Michigan; LA Biomedical Research Institute at Harbor–UCLA Medical Center, Torrance; University of California at San Diego, San Diego; CoTherix, Inc., South San Francisco, California; Baylor University, Houston, Texas; Duke University Medical Center, Durham, North Carolina; University of Pittsburgh, Pittsburgh, Pennsylvania; University of Colorado Health Sciences Center, Denver, Colorado; and Columbia University College of Physicians and Surgeons, New York, New York
Correspondence and requests for reprints should be addressed to Vallerie V. McLaughlin, M.D., Associate Professor of Medicine, Director, Pulmonary Hypertension Program, University of Michigan, 1500 East Medical Center Drive, Women's Hospital–Room L3119, Ann Arbor, MI 48109-0273. E-mail: vmclaugh{at}umich.edu
Rationale: 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 µg) 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.
Measurements and Main 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 · s · 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.
Key Words: bosentan • iloprost • pulmonary arterial hypertension
| AT A GLANCE COMMENTARY
Scientific Knowledge on the Subject
Very few controlled data regarding combination therapy for pulmonary arterial hypertension are available.
What This Study Adds to the Field
This study demonstrates the safety and efficacy of the addition of iloprost in patients with pulmonary arterial hypertension who remain symptomatic while on bosentan.
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