Risk of stroke associated with inhaled ipratropium bromide in chronic obstructive pulmonary disease: a population-based nested case-control study

Int J Cardiol. 2012 Jul 12;158(2):279-84. doi: 10.1016/j.ijcard.2012.02.012. Epub 2012 Mar 3.


Background: Cardiovascular safety concerns about inhaled ipratropium bromide have recently been raised. Nonetheless, the specific stroke risk associated with ipratropium use has not been evaluated thoroughly.

Methods: This was a population-based nested case-control study analyzing data from the National Health Insurance Research Database in Taiwan. A cohort of 15,396 newly-diagnosed chronic obstructive pulmonary disease (COPD) patients was included between 2001 and 2007, in which 1477 cases of incident hospitalization for stroke were identified. Each case was individually matched to four randomly-selected controls based on age, sex, and cohort entry date. Conditional logistic regressions were used to estimate the odds ratio (OR) for risk of stroke-related hospitalization associated with ipratropium use.

Results: Any use of ipratropium within the 6 months before the index date was associated with an increased risk of stroke compared with nonuse (adjusted OR, 2.02; 95% CI, 1.71 to 2.41). The observed risk remained significant regardless of accumulated doses. Additionally, use of ipratropium within 30 days before the index date resulted in the greatest risk (adjusted OR, 2.97 95% CI, 2.27 to 3.88). Furthermore, an increased risk of stroke was found for ipratropium regimens involving concomitant use of inhaled short-acting β(2)-agonists (SABAs; adjusted OR, 2.18; 95% CI, 1.81 to 2.62) or theophyllines (adjusted OR, 1.79; 95% CI, 1.42 to 2.26).

Conclusions: Use of ipratropium is associated with an increased risk of stroke in COPD patients. Clinicians should be alert to that risk when prescribing ipratropium, especially for those receiving ipratropium more recently or those with concomitant use of SABAs or theophyllines.

MeSH terms

  • Administration, Inhalation
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Humans
  • Ipratropium / administration & dosage
  • Ipratropium / adverse effects*
  • Male
  • Middle Aged
  • Population Surveillance* / methods
  • Pulmonary Disease, Chronic Obstructive / epidemiology*
  • Retrospective Studies
  • Risk Factors
  • Stroke / chemically induced*
  • Stroke / epidemiology*


  • Ipratropium