Use Long-Acting Beta-Agonists as Mainstay of COPD Treatment

By Walter Alexander

SAN FRANCISCO—Accumulating evidence points to use of long-acting bronchodilators as the mainstay of chronic obstructive pulmonary disease (COPD) treatment. These agents are safe and help alleviate the hyperinflation that is increasingly being seen as a key COPD element, reported experts at the American Thoracic Society annual meeting.

"Short-acting bronchodilators should be reserved for rescue medication," stated symposium moderator Anthony Anzueto, MD, professor of medicine, University of Texas, San Antonio, adding that the short-acting agents do not prevent COPD progression.

Bartolome R. Celli, MD, professor of medicine at Tufts University, Boston, sought to answer this question: Although it is clear that antiinflammatory drugs help in COPD by reducing the characteristic bronchial inflammation of exacerbations, why is it that bronchodilators also reduce exacerbations?

Dr Celli suggested that bronchodilators help mediate the hyperinflation that ensues when the progression of disease, over years and decades, leads to the loss of lung elastic recoil, air trapping, and static hyperinflation, and the patient is breathing at a higher lung volume. During an exacerbation, triggering of systemic inflammation stimulates a syndrome that is not too dissimilar to exercise in the lab. "The only difference is that the patient can't get off the bike.But?it is possible that if we can influence hyperinflation, you may be able to decrease the threshold level at which patients perceive shortness of breath."

Other experts at the meeting echoed Dr Celli's emphasis on the role oflong-acting beta-agonists in relieving hyperinflation. "Long-acting bronchodilators," stated James Donahue, MD, professor of medicine, University of North Carolina, Chapel Hill, "don't just improve airflow, they deflate the lung."

Regular closing of the airways takes energy, requires more rescue medication, and may lead to more symptoms. "It's better to keep the airways open the whole time—that's the advantage of the 24-hour agents," he said.

Dr Donahue presented results of a 12-month clinical trial comparing once-daily bronchodilation with the recently approved arformoterol (Brovana), administered via nebulization (50 μg; n = 528), versus twice-daily dosing with the bronchodilator salmeterol (42 μg by metered-dose inhaler; n = 265).

All patients (aged ≥35 years) had a confirmed diagnosis of COPD. The study looked at adverse events and changes in forced expiratory volume in 1 second (FEV₁). Mean FEV₁ at baseline was 38.9% in the arformoterol group and 37.0% in the salmeterol group. The once-daily arformoterol dose used in the study was 1.7 times greater than the approved dose of 15 mg twice daily.

Overall, the frequency of adverse events was similar with arformoterol and salmeterol, as was the frequency of serious adverse events (12.7% and 12.5%, respectively), and serious adverse respiratory events (5.5% and 5.7%). COPD exacerbations did not increase in frequency over 12 months. Stable decreases in rescue albuterol use occurred in both groups (arformoterol: approximately ?1.1 d/wk, approximately ?1.0 puffs/d; salmeterol: approximately ?0.9 d/wk, approximately ?0.9 puffs/d).

Although serial spirometry, which measures FEV₁ predose and then 1, 2, 3, and 4 hours postdose at weeks 0, 13, 26, 39, and 52, demonstrated slightly higher favorable peak percent change in FEV₁ with arformoterol from predose over 4 hours, this finding was not clinically significant, Dr Donohue said. A total of 3 deaths occurred in the arformoterol group compared with 2 in the salmeterol group.

Dr Donahue said, "The use of long-acting bronchodilators was not associated with loss of COPD control over 12 months, as indicated by stability in rescue medication use and frequency of COPD exacerbations."

IMWR

He told, "This higher dose would work once a day, no question. With all the concerns about beta-agonist safety, this study is reassuring."

KEY POINTS

• Long-acting bronchodilators are the mainstay of COPD therapy.
• Short-acting bronchodilators should only be used as a rescue medication.