title: Comparative Cardiovascular and Cerebrovascular Safety of Inhaled Long-Acting Bronchodilators in Patients with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study.
abstract: OBJECTIVE
  Inhaled long-acting bronchodilators are commonly used as maintenance therapy in chronic obstructive pulmonary disease (COPD). We compared the risk of cardiovascular and cerebrovascular events among patients with COPD treated with inhaled long-acting bronchodilator monotherapy and combination therapy.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  A population-based health care database from Taiwan.
  
  
  METHODS
  Individuals with COPD who initiated long-acting muscarinic antagonists (LAMAs) alone, long-acting β-2 agonists (LABA) alone, and LABA and LAMA in combination between 2001 and 2010.
  
  
  RESULTS
  We used Cox regression models to compare a composite cardiovascular outcome, defined as hospitalization for acute myocardial infarction, congestive heart failure, and cerebrovascular diseases among the three treatment groups, adjusting for potential confounders. Among a cohort of 3458 study-eligible patients, we identified 505 composite cardiovascular events during 10,590 patient-years of follow-up. In the primary analysis which considered first exposure carried forward, LABA alone and LAMA alone were associated with similar risks of the composite outcome (hazard ratio [HR] 1.09; 95% confidence interval [CI] 0.87-1.37). The HR comparing LABA and LAMA in combination with LAMA alone was 1.13 (95% CI 0.60-2.13) and to LABA alone was 1.03 (95% CI 0.55-1.92). The secondary analysis in which we allowed patients to reenter the cohort upon treatment change yielded similar results, but with slightly higher HRs comparing LABA and LAMA in combination with LAMA alone (HR 1.26, 95% CI 0.74-2.15) and to LABA alone (HR 1.31, 95% CI 0.80-2.13).
  
  
  CONCLUSIONS
  Our results suggest similar cardiovascular and cerebrovascular safety of LABA and LAMA when agents are used alone. Additional studies are needed to rule out potential risk associated with inhaled long-acting bronchodilator combination therapy.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.|Center of Comparative Effectiveness Research, National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yaa-Hui
authors.initials: YH
authors.lastname: Dong
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Hsuin
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Gagne
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Hsu
authors.affiliation: Center of Comparative Effectiveness Research, National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei, Taiwan.|Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Mei-Shu
authors.initials: MS
authors.lastname: Lai
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002561:Cerebrovascular Disorders / Q000139:chemically induced*; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D012189:Retrospective Studies
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D018727:Muscarinic Antagonists
keywords: cardiovascular safety; cerebrovascular safety; chronic obstructive pulmonary disease; cohort study; inhaled long-acting bronchodilators