• Todd A Lee, A Simon Pickard, David H Au, Brian Bartle, and Kevin B Weiss.
• Hines Veterans Affairs Hospital, Hines, Illinois 60141, USA. todd.lee@va.gov
• Ann. Intern. Med. 2008 Sep 16; 149 (6): 380390380-90.

BackgroundConcerns exist regarding increased risk for mortality associated with some chronic obstructive pulmonary disease (COPD) medications.ObjectiveTo examine the association between various respiratory medications and risk for death in veterans with newly diagnosed COPD.DesignNested case-control study in a cohort identified between 1 October 1999 and 30 September 2003 and followed through 30 September 2004 by using National Veterans Affairs inpatient, outpatient, pharmacy, and mortality databases; Centers for Medicare & Medicaid Services databases; and National Death Index Plus data. Cause of death was ascertained for a random sample of 40% of those who died during follow-up. Case patients were categorized on the basis of all-cause, respiratory, or cardiovascular death. Mortality risk associated with medications was assessed by using conditional logistic regression adjusted for comorbid conditions, health care use, and markers of COPD severity.SettingU.S. Veterans Health Administration health care system.Participants32 130 case patients and 320 501 control participants in the all-cause mortality analysis. Of 11 897 patients with cause-of-death data, 2405 case patients had respiratory deaths and 3159 case patients had cardiovascular deaths.MeasurementsAll-cause mortality; respiratory and cardiovascular deaths; and exposure to COPD medications, inhaled corticosteroids, ipratropium, long-acting beta-agonists, and theophylline in the 6 months preceding death.ResultsAdjusted odds ratios (ORs) for all-cause mortality were 0.80 (95% CI, 0.78 to 0.83) for inhaled corticosteroids, 1.11 (CI, 1.08 to 1.15) for ipratropium, 0.92 (CI, 0.88 to 0.96) for long-acting beta-agonists, and 1.05 (CI, 0.99 to 1.10) for theophylline. Ipratropium was associated with increased cardiovascular deaths (OR, 1.34 [CI, 1.22 to 1.47]), whereas inhaled corticosteroids were associated with reduced risk for cardiovascular death (OR, 0.80 [CI, 0.72 to 0.88]). Results were consistent across sensitivity analyses.LimitationsCurrent smoking status and lung function were not measured. Misclassification of cause-specific mortality is unknown.ConclusionThe possible association between ipratropium and elevated risk for all-cause and cardiovascular death needs further study.

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