August 24, 2011 — Azithromycin given daily for 1 year in addition to usual treatment reduces exacerbations and improves quality of life in selected patients with chronic obstructive pulmonary disease (COPD) but causes hearing decrements in a small percentage of patients, according to the results of a randomized controlled trial reported in the August 25 issue of the New England Journal of Medicine.
"Acute exacerbations adversely affect patients with ...COPD," write Richard K. Albert, MD, from Denver Health in Denver, Colorado, and colleagues from the COPD Clinical Research Network. "Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases."
The goal of this study was to examine the association of azithromycin use with frequency of exacerbations in patients with COPD who had an increased risk for exacerbations but no evidence of hearing impairment, resting tachycardia, or risk for corrected QT interval prolongation.
Of 1577 patients screened, 1142 (72%) were randomly assigned to receive, in addition to their usual care, 250 mg of azithromycin daily (n = 570), or daily placebo (n = 572) for 1 year. The 1-year follow-up rate was 89% for patients receiving azithromycin and 90% for those receiving placebo.
In the azithromycin group, the median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 - 313) vs 174 days (95% CI, 143 - 215) in the placebo group (P < .001). There were 1.48 exacerbations per patient-year in the azithromycin group and 1.83 per patient-year in the placebo group (P = .01), with a hazard ratio of 0.73 in the azithromycin group for having an acute COPD exacerbation (95% CI, 0.63 - 0.84; P < .001).
Compared with the placebo group, the azithromycin group had a greater improvement in St. George's Respiratory Questionnaire scores. Mean decrease was 2.8 ± 12.8 vs 0.6 ± 11.4 units (P = .004) on a scale of 0 to 100, with lower scores reflecting better functioning. The azithromycin group also fared better in the percentage of participants with more than the minimal clinically important difference of −4 units (43% vs 36%; P = .03). However, patients in the azithromycin group were more likely to have hearing decrements than those in the placebo group (25% vs 20%; P = .04).
"Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects," the study authors write. "Although this intervention could change microbial resistance patterns, the effect of this change is not known."
Limitations of this study include evaluation of only a single-dose regimen, incomplete collection of sputum samples, and study duration limited to 1 year.
'Do Good, Not Harm'
An accompanying editorial by Nikolaos M. Siafakas, MD, PhD, from the Department of Thoracic Medicine, Medical School at the University of Crete in Crete, Greece, discusses prevention of COPD exacerbations.
"[I]f azithromycin is going to be used in patients who are known to have frequent exacerbations of COPD, then the local antibiotic resistance patterns should be closely monitored," Dr. Siafakas writes. "It also makes sense to ask whether, in such patients, subsequent exacerbations should be treated empirically with a different class of antibiotics. On balance, however, the long-term use of azithromycin to prevent acute exacerbations of COPD would not seem to be at odds with the classical advice of Hippocrates, 'Ωφελέειν ου Βλάπτειν' — 'Do good, not harm.'"
The National Institutes of Health supported this study. The COPD Clinical Research Network is supported by a Cooperative Agreement from the Division of Lung Diseases of the National Heart, Lung, and Blood Institute. Dr. Albert has received consulting fees from Gilead Sciences, fees for expert testimony from the Bruce Fagel Law Firm, and royalties from Elsevier, and being named on a patent pending for a device that provides continuous monitoring of the elevation of the head of the bed (Denver Health and the University of Colorado). The other study authors have disclosed various financial relationships with such commercial entities as Novartis Pharmaceuticals, Forest Pharmaceuticals, Boehringer Ingelheim, Roche, GlaxoSmithKline, Phillips Pharmaceuticals, Theratechnologies, Breathe Technologies, AstraZeneca, and Boston Scientific. A complete description of disclosures is available in the original article.
N Engl J Med. 2011;365:689-698, 753-754.
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