Risk of Arrhythmias Associated with Inhaled Anticholinergics in Young Individuals with Asthma

Context: Asthma is a common chronic condition with significant morbidity. Inhaled anticholinergics (IACs) are being investigated for maintenance therapy in asthma. However, little is known about the cardiovascular safety of these drugs in asthma. Objective: To evaluate the risk of arrhythmias associated with IAC use in young individuals with asthma. Design, Setting, and Patients: A population-based, nested case-control study of new users of asthma controller medications was conducted. Patients aged 5 to 24 years were identified between July 1997 and April 2010 in the IMS LifeLink™ Health Plan Claims Database for inclusion in the study. Cases were newly diagnosed with arrhythmia and were matched with up to 10 controls based on age, gender, geographic region, and quarter and year of first controller medication dispensing. Active use of anticholinergics was defined as days supply for a prescription extending through the event date. Main Outcome Measure: New arrhythmia diagnoses Results: Among 283,429 individuals with asthma, there were 7,656 cases matched to 76,304 controls. The majority of those included were female (58.8%) and older than 12 years (73.3%). Active exposure of IACs was observed in 0.69% of cases and 0.18% of controls. Active use was associated with a 1.56-fold increase in arrhythmia risk compared with non-active/nonusers (Adjusted Odds Ratio (ORadj), 1.56; 95% CI, [1.08–2.25]). Risk was highest among active users of ipratropium (ORadj, 1.59 [1.08–2.33]) compared with tiotropium (ORadj, 1.20 [0.29–4.89]) and combination ipratropium and short-acting beta-agonists (ORadj, 1.20 [0.74–1.94]). Active high dose users of IACs (>0.114mg ipratropium equivalents) had a 69% increase in risk (ORadj, 1.69 [1.10–2.59]) whereas the added risk for active users on low dose (≤ 0.114mg ipratropium equivalents) (ORadj, 1.22 [0.53–2.65]) was not statistically significant. Conclusion: IAC use was associated with an increased risk of arrhythmias in young individuals with asthma