PURPOSE: Studies suggest an association between inhaled short-acting β2-agonists and the risk of cardiovascular events (CVEs). The cardiovascular safety of inhaled long-acting β2-agonists (LABAs) in patients with chronic obstructive pulmonary disease (COPD) remains unclear.
METHODS: To assess the association between LABAs and the risk of CVEs (acute coronary syndrome, heart failure or cardiac dysrhythmia) in COPD patients, we performed a nested case-control study within a cohort of Veterans Affairs patients 40-100 years of age, newly diagnosed with COPD between October 1, 1998 and September 30, 2003(n=104,459). Subjects were followed-up until the earliest of a CVE, death or September 30, 2004. Cases were subjects hospitalized with a primary diagnosis of CVE. For each case, we randomly selected 5 controls matched with cases on age group (5-year intervals) and time since diagnosis of COPD. Cumulative LABA exposure was calculated as the number of 30-day LABA equivalents (50mcg salmeterol or 12mcg formoterol b.i.d for 30 days), split at the median, and grouped into 0, ≤ 4 and >4 LABA equivalents. Separate conditional logistic regression models were used to estimate the rate ratio (RR) and 95% confidence interval associated with ever exposure and cumulative exposure. We adjusted for age, fiscal year of COPD diagnosis, and use of theophylline, inhaled corticosteroids, anticholinergics and oral or nebulized b2-agonists.
RESULTS: 6,954 cases were matched with 34,770 controls. The population was predominantly male (cases=98.6%; controls=97.5%), the average age was 69.8years(SD=10.25) and average follow-up time was 1.47years. The adjusted RR comparing those ever exposed versus never exposed to LABAs was 1.02 (95% CI 0.90 to 1.15) and the adjusted RR associated with grouped cumulative exposure was 1.01 (95% CI 0.93 to 1.09).
CONCLUSION: LABAs do not appear to significantly increase the risk of CVEs in COPD patients. Understanding how risk factors such as hypertension, diabetes, hyperlipidemia, and preexisting cardiovascular disease affect this association is an important next step.
CLINICAL IMPLICATIONS: When prescribing LABAs for patients with COPD, clinicians should consider the potential for an increased risk of CVEs.
DISCLOSURE: Sarika Ogale, None.