Prostanoid therapy for pulmonary arterial hypertension
David B. Badesch, MD*,*,
Vallerie V. McLaughlin, MD ,
Marion Delcroix, MD ,
CarmineDario Vizza, MD ,
Horst Olschewski, MD||,
Olivier Sitbon, MD¶ and
Robyn J. Barst, MD
* University of Colorado Health Sciences Center, Denver, Colorado, USA
University of Michigan, Ann Arbor, Michigan, USA
University Hospital Gasthuisberg, Leuven, Belgium
University of Roma "La Sapienza," Rome, Italy
|| University Hospital, Justus-Liebig-University, Giessen, Germany
¶ Hôpital Antoine Béclère, Clamart, France
Columbia University College of Physicians and Surgeons, New York, New York, USA
Manuscript received November 26, 2003;
accepted February 3, 2004.
*
Reprint requests and correspondence: Dr. David B. Badesch, Divisions of Pulmonary Sciences and Critical Care Medicine, and Cardiology, University of Colorado Health Sciences Center, Box C-272, 4200 East Ninth Avenue, Denver, Colorado 80262, USA.
David.Badesch{at}UCHSC.edu
Prostanoids have played a prominent role in the treatment of pulmonary arterial hypertension (PAH). Several compounds and methods of administration have been studied: chronic intravenously infused epoprostenol, chronic subcutaneously infused treprostinil, inhaled iloprost, and oral beraprost. Chronic intravenous epoprostenol therapy has had a substantial impact on the clinical management of patients with severe PAH. It improves exercise capacity, hemodynamics, and survival in patients with idiopathic pulmonary arterial hypertension (IPAH). It also improves exercise capacity and hemodynamics in patients with PAH occurring in association with scleroderma. The complexity of epoprostenol therapy (chronic indwelling catheters, reconstitution of the drug, operation of the infusion pump, and others) has led to attempts to develop other prostanoids with simpler modes of delivery. Treprostinil, a stable prostacyclin analogue with a half-life of 3 h, has been developed for subcutaneous delivery. It has beneficial effects on exercise and hemodynamics, which depend somewhat on the dose achieved. This, in turn, is determined by the patient's ability to tolerate the drug's side effects, including pain and erythema at the infusion site. Inhaled iloprost therapy may provide selectivity of the hemodynamic effects to the lung vasculature, thus avoiding systemic side effects. In a randomized and controlled trial, iloprost resulted in improvement in a combined end point incorporating the New York Heart Association functional class, 6-min walk test, and deterioration or death. Beraprost is the first orally active prostacyclin analogue. In the first of two randomized controlled trials, beraprost increased exercise capacity in patients with IPAH, with no significant changes in subjects with associated conditions. Hemodynamics did not change significantly, and no difference in survival was detected between the two treatment groups. The second study showed that beraprost-treated patients had less disease progression at six months and confirmed the results of the previous trial. However, this improvement was no longer present at 9 or 12 months. In conclusion, though treatment with prostanoids is complicated by their generally short half-lives and complicated drug delivery systems, they continue to play an important role in the treatment of PAH.
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Abbreviations and Acronyms
| | IPAH | = idiopathic pulmonary arterial hypertension | | IV | = intravenous | | NO | = nitric oxide | | NYHA | = New York Heart Association | | PAH | = pulmonary arterial hypertension | | PPH | = primary pulmonary hypertension |
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