Daily azithromycin prevented acute exacerbations of chronic obstructive pulmonary disease when it was added to usual treatment in a 1-year study, thus improving patients’ quality of life, according to a report in the Aug. 25 issue of the New England Journal of Medicine.
The drug also cut the colonization of certain respiratory pathogens. On the downside, it increased colonization with macrolide-resistant organisms and induced hearing decrements in approximately 5% of patients, said Dr. Richard K. Albert, professor of medicine at the University of Colorado at Denver and chief of medicine at Denver Health, and his associates.
"Given the deleterious effects of acute exacerbations of COPD with respect to the risk of death, quality of life, loss of lung function, and cost of care, adding azithromycin to the treatment regimen [of at-risk patients] is a valuable option," they noted.
However, QTc prolongation is a contraindication to the drug, and patients who are at risk for the cardiac disorder should be monitored if they are given azithromycin. Hearing also should be monitored in all patients. "In addition, it should be recognized that the long-term effects of this treatment on microbial resistance in the community are not known," the investigators said.
Macrolide antibiotics like azithromycin have immunomodulatory and anti-inflammatory properties in addition to their antibacterial action. Several small studies have examined their use in preventing acute exacerbations of COPD, with conflicting results. "Accordingly, we conducted a large, randomized trial to test the hypothesis that azithromycin decreases the frequency of acute exacerbations of COPD when added to the usual care of these patients," said Dr. Albert and his colleagues in the COPD Clinical Research Network.
The prospective study involved 1,142 patients aged 40 years and older who were at risk for acute exacerbations and were randomly assigned to receive either 250 mg of oral azithromycin (570 subjects) or an identical-looking placebo (572 subjects) once daily for 1 year. All were already using inhaled glucocorticoids, long-acting beta-agonists, muscarinic antagonists, and/or continuous supplemental oxygen.
These subjects were followed at 17 sites associated with academic health centers across the United States.
The primary outcome measure – time to the first acute exacerbation of COPD – was significantly increased in the patients taking azithromycin (266 days), compared with those taking placebo (174 days). The hazard ratio of having an acute exacerbation per patient-year was 0.73 in the azithromycin group, compared with the placebo group.
These differences remained significant after the data were adjusted to account for differences between the two groups in sex, forced expiratory volume in 1 second (FEV1), age, and smoking status, the researchers said (N. Engl. J. Med. 2011;365:689-98).
There were 1,641 acute exacerbations of COPD during the study, and the number was significantly lower in the active-treatment group (741) than in the placebo group (900). "The number needed to treat to prevent one acute exacerbation of COPD was 2.86," they said.
More patients in the azithromycin group than in the placebo group showed significant improvements in quality of life scores.
Benefits Appear to Outweigh Risks
The finding that the interval before the first acute exacerbation of COPD was almost twice as long in patients taking azithromycin as in those taking placebo "tips the scales toward the benefits of treatment," Dr. Nikolas M. Siafakas said.
The risk of microbial resistance associated with long-term use of the drug "must be considered," but does not outweigh the benefits. "Acute exacerbations of COPD are devastating, life-threatening events; the 30-day mortality is greater than that with acute MI (26% vs. 7.8%)." Exacerbations also dramatically change the course of COPD, with a rapid decline in lung function and worsening quality of life. "They also represent a substantial economic burden to society," he noted.
Dr. Siafakas is in the department of thoracic medicine at the University of Crete, Heraklion, Greece. He reported ties to Boehringer Ingelheim, GlaxoSmithKline, Chiesi, AstraZeneca, ELPEN, HELP, and Nycomed. These remarks were adapted from his editorial accompanying Dr. Albert’s report (N. Engl. J. Med. 2011;365:753-4).
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