Bronchodilator Use and the Risk of Arrhythmia in COPD: Part 2: Reassessment in the Larger Quebec Cohort

Abstract

A previous study suggested a potential increased risk of cardiac arrhythmia with new use of long-acting β-agonists and ipratropium bromide in patients with COPD, although conclusions were limited by the small cohort size. We reassessed this association in a larger cohort formed from the health-care databases of the province of Quebec, Canada. We identified a cohort of patients with COPD aged ≥ 67 years who began treatment between 1990 and 1999 and followed them until December 2003. A nested case-control approach matched each subject who developed severe arrhythmia during follow-up with 20 control subjects from the cohort on age, sex, and calendar time. The rate ratio (RR) of arrhythmia associated with new use of bronchodilators was estimated using conditional logistic regression, adjusting for COPD disease severity, cardiovascular disease, and other comorbidities. The cohort included 76,661 patients with COPD, of whom 5,307 developed an arrhythmia (10.3 arrhythmias per 1,000 per year), 621 of which were fatal. The rate of cardiac arrhythmias was elevated with the new use of short-acting (RR, 1.27; 95% CI, 1.03-1.57) and long-acting (RR, 1.47; 95% CI, 1.01-2.15) β-agonists. The rate was slightly elevated, although not statistically significantly, with new use of ipratropium bromide (RR, 1.23; 95% CI, 0.95-1.57) and methylxanthines (RR, 1.28; 95% CI, 0.93-1.77). These effects waned with longer-term use. New use of short- and long-acting β-agonists may slightly increase the risk of cardiac arrhythmia in patients with COPD. It remains unclear whether ipratropium bromide also increases this risk, despite the use of a larger study population.