Lee TA (Hines VA Hospital), Pickard AS
(Hines VA Hospital), Bartle B
(Hines VA Hospital), Weiss KB
(Hines VA Hospital)
Safety questions have been raised about several medications used in treating chronic obstructive pulmonary disease (COPD). Our objective was to examine the association between medication use and risk of cause-specific mortality, namely respiratory-related and cardiovascular-related deaths.
We used a nested case-control study in patients with new diagnoses (to minimize COPD severity differences) of COPD from 1999 to 2003 that received COPD medications from the VA. We identified 32,130 patients that died prior to September 2004 and randomly sampled 40% to ascertain cause of death from National Death Index Plus data. Cases were those with respiratory-related or cardiovascular-related deaths. Up to ten controls, matched on sex, age, region of the country, and diagnosis year were selected per case. Analyses were done separately for cardiovascular and respiratory-related deaths. Exposure to COPD medications, specifically long-acting beta-agonists (LABAs), inhaled corticosteroids (ICS), ipratropium (IPRA) and theophylline (THEO) was defined in the six months preceding the event date. Mortality risk associated with medications was assessed using conditional logistic regression, while adjusting for comorbidities, health service use, and markers of COPD severity.
From 11,897 cases with cause of death data, the underlying cause was respiratory-related in 2,361 persons and cardiovascular-related in 3,159. Adjusted odds of respiratory-related mortality associated with medications were: LABA OR=1.19 (95% CI, 1.03, 1.37); ICS OR=0.94 (0.84, 1.05); IPRA OR=1.11 (1.00, 1.24); THEO OR=1.81 (1.54, 2.12). For cases with cardiovascular-related death, adjusted odds for COPD medications were: LABA OR=0.92 (0.81, 1.05); ICS OR=0.78 (0.71, 0.86); IPRA OR=1.43 (1.31, 1.57); THEO OR=1.16 (0.99, 1.35). When restricted to those 65 years and older, results were similar to the full cohort.
We found an increased risk of respiratory-related mortality among patients treated with LABAs and theophylline. In addition, ipratropium was associated with a significant increase in the risk of cardiovascular-related mortality, while inhaled corticosteroids were associated with a marked decrease in the risk of cardiovascular deaths.
The results of this study raise important questions about the safety of medications used in treating COPD. Better understanding of the risks involved with these medications can help clinicians and patients make more informed decisions.