AUTHOR: David J. Pierson, MD, Professor Emeritus, Pulmonary and Critical Care Medicine, University of Washington, Seattle; Physician Editor, Critical Care Alert
PEER REVIEWER: WilliamThompson, MD, Associate Professor of Medicine, University of Washington, Seattle
SYNOPSIS: In this study of administrative data from patients admitted to 421 U.S. hospitals with acute chronic obstructive pulmonary disease (COPD) exacerbations, 41% received long-acting bronchodilators, which are not recommended in this setting. Comparison with patients who did not receive the long-acting agents showed no evidence for clinical or economic benefit from their use.
SOURCE: Lindenauer PK, et al. Use and outcomes associated with long-acting bronchodilators among patients hospitalized for chronic obstructive pulmonary disease. Ann Am Thorac Soc 2014 Aug 28. [Epub ahead of print].
This was a retrospective cohort study of 421 U.S. hospitals participating in the Premier Inpatient Database. It focused on patients hospitalized with exacerbations of chronic obstructive pulmonary disease (COPD) between January 1, 2010 and June 30, 2011. Its purpose was to determine the frequency with which long-acting bronchodilators (LABDs, which are approved and recommended for use in long-term management of stable patients) are used in this setting.
The Premier Inpatient Database includes approximately 15% of admissions to acute care U.S. hospitals, and it has been used extensively in comparative effectiveness research for COPD. The authors reviewed data for all patients older than age 40 with a principal discharge diagnosis consistent with acute COPD exacerbation, who were also treated with systemic corticosteroids. Patients were excluded if they were intubated (in which case LABDs could not be administered), transferred, or discharged within 2 days. The primary outcome variable was a composite measure of treatment failure (invasive mechanical ventilation, in-hospital death, or readmission within 30 days); secondary outcomes included length of stay and hospital costs. The authors used propensity score analysis to compare patients who received LABDs to those who did not, in addition to multiple other statistical means for reducing confounders.
Of the 77,378 patients included in the analysis (mean age 69; 58% female; 77% white), 31,725 (41%) received LABDs during their hospital stay. Of the patients, 48% of these received long-acting beta agonists alone, 21% received tiotropium alone, and 31% received both. Treatment failure, as defined for this study, occurred in 13.4% of patients, including 2.2% who required invasive mechanical ventilation, 3.4% who received noninvasive ventilation, 1.8% who died, and 8.6% who were readmitted within 30 days. Patients treated with LABDs tended to be younger, to have a slightly lower comorbidity score, and to have been admitted previously for COPD exacerbations (all statistically significant differences). These patients also received inhaled corticosteroids in the hospital much more often than patients not treated with LABDs (82% vs 12%; P < 0.0001).
In the propensity-matching analysis (which could be done for 81% of the LABD-receiving patients) there were no significant differences in treatment failure, a composite measure of complications, length of stay, or hospital costs between the two groups. Secondary analysis revealed no outcome associations for either type of LABD, separately or in combination, nor for cardiovascular complications, in comparison with patients receiving short-acting bronchodilators alone. The authors conclude that LABDs are commonly prescribed to patients hospitalized with acute COPD exacerbations, but that this is not associated with improved clinical or economic outcomes.
Drugs shown to be effective in, and FDA-approved for, use in one pulmonary condition tend to metastasize to other conditions with similar features for which both evidence for clinical effectiveness and approval for use are lacking. The widespread prescription of montelukast for patients with COPD, and of anticholinergic agents in the long-term management in asthma, come to mind as examples. Long-acting bronchodilators — both beta agonists and anticholinergics — have been shown effective in the long-term management of COPD, but not in acute exacerbations. The present study’s finding that 41% of COPD patients hospitalized for acute exacerbations received long-acting agents suggests that this is another example of this “indication creep.”
A natural tendency to step up pharmacologic management — adding new agents while continuing those already in use — during a worsening of the patient’s condition, as well as administrative pressure to make sure that established outpatient regimens are not lost track of when patients are hospitalized, may contribute to this disappointingly high rate of non-recommended drug administration.