For patients with pulmonary arterial hypertension (PAH), adding inhaled iloprost to treatment with bosentan—two different classes of drugs often used individually to treat PAH—increases exercise capability, reduces clinical deterioration and, in some cases, improves diagnostic functional class by one stage.
The results of this randomized, multi-center study appear in the first issue for December 2006 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.
PAH is a debilitating and potentially fatal disease characterized by the progressive narrowing of blood vessels in the lungs. In 2000, there were 163,000 hospital discharges in which one diagnosis was PAH. Although it is more common in women, ages 21 to 40, it can affect men or women at any age.
Vallerie V. McLaughlin, M.D., of the University of Michigan Medical Center, and nine associates studied 65 PAH patients who were being treated with bosentan, an endothelin receptor antagonist that helps to increase blood flow in the lungs.
The researchers gave 32 patients both bosentan and inhaled iloprost, a prostacyclin analog. The remaining patients received bosentan and a placebo.
Every patient who received the combined therapy increased their six-minute walk distance by more than 98 feet. In addition, 11 climbed from functional class III to class II on the New York Heart Association PAH classification list, which measures how severely patients are limited by their disease. None of the patients in the combined treatment group experienced clinical deterioration by the end of the 12-week study.
Bosentan is often used for initial therapy due to its ease of administration. However, for patients who remain impaired on single drug treatment, Dr. McLaughlin calls the addition of inhaled iloprost is a “potentially attractive clinical option.”
“During the 12-week study, time to clinical worsening was significantly longer in iloprost-treated patients than in placbo patients,” she continued. “None of the iloprost patients met the predefined criteria for clinical worsening, compared with five of the 33 placebo patients.”
The investigators found the drug combination to be both safe and effective. They noted that syncope, a brief loss of consciousness due to a temporary insufficient flow of blood to the brain, was infrequent with the combination therapy, which may be an effect of bosentan.
Since inhaled iloprost therapy requires administration approximately six times per day, the researchers acknowledged that some patients could find this regimen inconvenient and expensive, given the additional cost of combining drugs.
PAH has no known cause and is difficult to diagnose. Symptoms include shortness of breath following exercise, excessive fatigue, dizziness, fainting, and weakness, with symptoms tending to worsen over time.
Contact: Vallerie V. McLaughlin, M.D., Associate Professor of Medicine, and Director, Pulmonary Hypertension Program, University of Michigan, 1500 East Medical Center Drive, Women’s Hospital—Room L3119, Ann Arbor, Michigan 48109-0273
Phone: (734) 615-4907
E-mail: vmclaugh@umich.edu
Journal
American Journal of Respiratory and Critical Care Medicine