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Ipratropium associated with increase risk of CV events

Clinical Question:
Is the use of ipratropium for chronic obstructive pulmonary disease associated with adverse cardiovascular events?

Bottom Line:
Recent exposure to inhaled ipratropium is associated with an increased risk of hospitalization for cardiovascular disease. The overall risk was 2.2 events per 100 patient-years, so the 29% increase in risk seen in this study amounts to fewer than 1 additional event per 100 person years. (LOE = 2b)

Reference:
Ogale SS, Lee TA, Au DH, Boudreau DM, Sullivan SD. Cardiovascular events associated with ipratropium bromide in COPD. Chest 2010;137(1):13-19  [PMID:19363211]

Study Design:
Cohort (prospective)

Funding:
Government

Setting:
Outpatient (any)

Synopsis:
Previous studies have found an association between use of inhaled anticholinergic agents, such as ipratropium bromide, and cardiovascular events and mortality. The authors of this VA study used a cohort of 82,717 patients who had a new diagnosis of chronic obstructive pulmonary disease and followed them up until their first hospitalization for a cardiovascular event or death or until the end of the study period, whichever came first. The average duration of follow up was 3.3 years. Only 0.024% of prescriptions were for tiotropium, so the results of the study apply to ipratropium only. Patients were classified by how much and how recently they had taken ipratropium. The mean age of patients was 67 years and 97% were men (this was a VA study, after all). In their analysis, the authors adjusted for cardiovascular risk factors, use of other medications, and measures of disease severity. This is important, because in an observational study it is possible that sicker patients were more likely to be given ipratropium. They found an increased risk of cardiovascular events (admission for acute coronary syndrome, heart failure, or arrhythmia) in patients with exposure to anticholinergics (hazard ratio = 1.29; 95% CI, 1.21-38). This increased risk was only seen among patients with exposure within the past 6 months, and not among those with more distant exposure. The association remained statistically significant regardless of history of prior cardiovascular disease or any use of inhaled corticosteroids in the past year.

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