title: Inhaled Pharmacotherapy and Stroke Risk in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Population Based Study Using Two-Stage Approach.
abstract: OBJECTIVE
  Patients with chronic obstructive pulmonary disease (COPD) are at higher risk of stroke than those without COPD. This study aims to explore the impact of inhaled pharmacotherapy on stroke risk in COPD patients during a three-year follow-up, using a nationwide, population-based study and a matched cohort design.
  
  
  METHODS
  The study cohort comprised 10,413 patients who had received COPD treatment between 2004 and 2006; 41,652 randomly selected subjects comprised the comparison cohort. Cox proportional hazard regressions and two-stage propensity score calibration were performed to determine the impact of various inhaled therapies including short-acting muscarinic antagonists, long-acting muscarinic antagonists, short-acting β-agonists (SABAs), long-acting β-agonists (LABAs), and LABA plus inhaled corticosteroid (ICS), on the risk after adjustment for patient demographic characteristics and comorbid disorders.
  
  
  RESULTS
  Of the 52,065 sampled patients, 2,689 (5.2%) developed stroke during follow-up, including 727 (7.0%) from the COPD cohort and 1,962 (4.7%) from the comparison cohort (p < 0.001). Treatment with SABA was associated with 1.67-fold (95% CI 1.45-1.91; p < 0.001) increased risk of stroke in COPD patients. By contrast, the cumulative incidence of stroke was significantly lower in those treated with LABA plus ICS than those treated without (adjusted hazard ratio 0.75, 95% CI 0.60-0.94, p = 0.014).
  
  
  CONCLUSIONS
  Among COPD patients, the use of inhaled SABA is associated with an increased risk of stroke, and combination treatment with inhaled LABA and ICS relates to a risk reduction. Further prospective research is needed to verify whether LABA plus ICS confers protection against stroke in patients with COPD.
authors.affiliation: Department of Mathematics, Soochow University, Taipei, Taiwan.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Lin
authors.affiliation: School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Chung
authors.affiliation: Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: You Shuei
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Department of Neurology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Yu
authors.affiliation: School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chun-Nin
authors.initials: CN
authors.lastname: Lee
authors.affiliation: School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Mauo-Ying
authors.initials: MY
authors.lastname: Bien
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D015331:Cohort Studies; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012306:Risk; D020521:Stroke / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D016019:Survival Analysis
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D018727:Muscarinic Antagonists