title: Cardiovascular safety of inhaled long-acting bronchodilators in individuals with chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  Chronic obstructive pulmonary disease (COPD) is a common and deadly disease. Long-acting inhaled β-agonists and anticholinergics, first-line medications for COPD, have been associated with increased risk of cardiovascular outcomes. When choosing between the medications, patients and physicians would benefit from knowing which has the least risk.
  
  
  OBJECTIVE
  To assess the association of these classes of medications with the risk of hospitalizations and emergency department visits for cardiovascular events.
  
  
  METHODS
  We conducted a nested case-control analysis of a retrospective cohort study. We compared the risk of events between patients newly prescribed inhaled long-acting β-agonists and anticholinergics, after matching and adjusting for prognostic factors.
  
  
  METHODS
  Health care databases from Ontario, the largest province of Canada, with a multicultural population of approximately 13 million.
  
  
  METHODS
  All individuals 66 years or older meeting a validated case definition of COPD, based on health administrative data, and treated for COPD from September 1, 2003, through March 31, 2009.
  
  
  METHODS
  New use of an inhaled long-acting β-agonist or long-acting anticholinergic.
  
  
  METHODS
  An emergency department visit or a hospitalization for a cardiovascular event.
  
  
  RESULTS
  Of 191 005 eligible patients, 53 532 (28.0%) had a hospitalization or an emergency department visit for a cardiovascular event. Newly prescribed long-acting inhaled β-agonists and anticholinergics were associated with a higher risk of an event compared with nonuse of those medications (respective adjusted odds ratios, 1.31 [95% CI, 1.12-1.52; P < .001] and 1.14 [1.01-1.28; P = .03]). We found no significant difference in events between the 2 medications (adjusted odds ratio of long-acting inhaled β-agonists compared with anticholinergics, 1.15 [95% CI, 0.95-1.38; P = .16]).
  
  
  CONCLUSIONS
  Among older individuals with COPD, new use of long-acting β-agonists and anticholinergics is associated with similar increased risks of cardiovascular events. Close monitoring of COPD patients requiring long-acting bronchodilators is needed regardless of drug class.
authors.affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada. andrea.gershon@ices.on.ca
authors.forename: Andrea
authors.initials: A
authors.lastname: Gershon
authors.forename: Ruth
authors.initials: R
authors.lastname: Croxford
authors.forename: Andrew
authors.initials: A
authors.lastname: Calzavara
authors.forename: Teresa
authors.initials: T
authors.lastname: To
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Stanbrook
authors.forename: Ross
authors.initials: R
authors.lastname: Upshur
authors.forename: Thérèse A
authors.initials: TA
authors.lastname: Stukel
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016022:Case-Control Studies; D018680:Cholinergic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D005260:Female; D006333:Heart Failure / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D008297:Male; D008991:Monitoring, Physiologic; D009864:Ontario; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012602:Scopolamine Derivatives / Q000008:administration & dosage* / Q000009:adverse effects; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D012602:Scopolamine Derivatives; D000069447:Tiotropium Bromide