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Wednesday 12 July 2006

A question about beta-agonists

By: Rachel Courtland

Some inhaled medications used to treat chronic obstructive pulmonary disorder, or COPD, may do more harm than good, according to a review of clinical trials performed by researchers at Cornell and Stanford universities.

The comparison of two types of medications, published online last week in the Journal of General Internal Medicine, found that the most commonly prescribed type carries a higher risk of hospitalization—as well as death‑from respiratory causes.

COPD, a chronic and progressive condition that reduces lung function, is actually a class of diseases that includes emphysema and chronic bronchitis. It is the fourth-leading cause of death in the United States. Bronchodilators, drugs delivered through inhalers, are often the first line of treatment, used to relax the muscles around the airways, relieving symptoms and sometimes slowing progression of the disease.

The study reviewed the results of 22 clinical trials of two classes of inhaled drugs, beta-agonists and anticholinergics, that are commonly prescribed for COPD. Compared with a placebo, anticholinergics reduced the risk of respiratory-related deaths by 73 percent; beta-agonists were found to more than double the risk of respiratory death. When researchers compared the drugs with each other, they found that COPD patients taking beta-agonists were twice as likely to be hospitalized, and also appeared more likely to die than patients taking anticholinergics. The results follow on the heels of previous work by the researchers in analyzing how the drugs affect asthma sufferers.

"There are two things you want to do: improve symptoms and improve control of the disease," says Shelley Salpeter, a clinical professor of medicine at Stanford University and lead author on the study. "Both kinds of drugs improve airflow immediately, but over the long run, the beta-agonists worsen control of the disease because [the body develops] tolerance." These drugs, Salpeter theorizes, may be helpful in opening the airways, and thus lessening symptoms of the disease, but may leave the lungs more prone to complications such as inflammation or infection.

The review examined studies of the beta-agonists metaproterenol (Alupent), formoterol (Foradil), salmeterol (Serevent, Advair) and albuterol (Alupent, Proventil, Ventolin, and others). The anticholinergics tiotropium (Spiriva) and ipratropium (Atrovent) were also studied.

In an E-mail, Salpeter said she would recommend that patients on beta-agonists tell their doctor they would like to switch to an anticholinergic inhaler, and also use an inhaled corticosteroid, which reduces inflammation. "I don't use beta-agonists in my practice at all," she said.

Other experts have reacted to the findings cautiously. "I don't think there are sufficient data to consider taking the drug off the market," says Stephen Lazarus, a professor of medicine at the University of California–San Francisco. "There is a fair amount of controversy about the value of metanalysis. It's a good thing to do, but it has to be taken with a grain of salt." James Donohue, a professor of medicine at the University of North Carolina School of Medicine in Chapel Hill, points to the preliminary results of a GlaxoSmithKline trial released in April, which found that, compared with a placebo, the beta-agonist Advair reduced overall deaths in COPD patients by 17 percent. He thinks that as long as people are using beta-agonists properly, along with corticosteroids to address inflammation, the drugs "are perfectly safe."

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