Lee TA (Hines VA Hospital), Ogale SS
(University of Washington), Sullivan SD
(University of Washington), Au D
(VA Puget Sound HCS)
Chronic obstructive pulmonary disease (COPD) is one of the most prevalent conditions among veterans older than 40 years of age. The safety of long-acting beta-agonists (LABAs) in the treatment of asthma has been questioned. The evidence regarding the risk of LABAs in patients with COPD is inconclusive. The objective of this study was to examine the risk of mortality in veterans with COPD who were exposed to LABAs.
We performed a cohort study of veterans greater than 40 years of age, newly diagnosed with COPD between October 1998 and September 2003. Subjects were followed until they died or September 30, 2004. We used Cox regression with time-dependent covariates to estimate the risk of all-cause mortality associated with exposure to LABAs within the past year, and to adjust for potential confounders including markers of COPD severity and cardiovascular risk. We explored effect-modification by inhaled corticosteroid (ICS) use within the past year, pre-existing cardiovascular disease (CVD), and race.
We identified a total of 104,354 persons with a diagnosis of COPD (mean age = 66.7 yrs). Patients were followed an average of 3 years and there were 23,364 deaths. The adjusted hazard ratio (HR) of all-cause mortality comparing patients exposed vs. unexposed to LABAs within the past year was 1.07 (95% CI 1.01 to 1.14). Effect modification by ICS use within the past year was statistically significant (HR (95% CI), ICS users: 1.00 (0.92 to 1.09) and ICS non-users: 1.14 (1.05 to 1.24). Effect modification by pre-existing CVD and race was not statistically significant.
We found an increased risk of all-cause mortality associated with the use of LABAs within the past year in patients with COPD. The increased risk was limited to patients who had not used ICS within the past year.
The findings from this analysis raise important questions about the safety of LABAs in the treatment of COPD when not used in combination with inhaled corticosteroids. This information is important for patients and providers when making decisions on treatment options for COPD.