title: Long-acting Inhaled Bronchodilator and Risk of Vascular Events in Patients With Chronic Obstructive Pulmonary Disease in Taiwan Population.
abstract: A combination of long-acting anticholinergic agents (LAACs) and long-acting β2-adrenergic receptor agonist (LABA) is effective in improving lung function in chronic obstructive pulmonary disease (COPD) compared with monotherapy. However, evidence on whether this combination increases the incidence of stroke or other cardiac events remains sparse. The objective of the present study was to investigate the incidence of stroke and other cardiovascular diseases in COPD patients treated with LAAC, LABA, or a combination of the 2.We conducted this population-based study using the Taiwan National Health Insurance Research Database (1997-2008), identifying COPD patients and their prescribed medication from the International Classification of Disease, Ninth Revision codes 490-492 or 496. A multivariate Cox proportional-hazards model was used to compare the risk of stroke and other cardiovascular diseases over the 11-year period after treatment with LAAC or LABA only or in combination.Of the 596 COPD patients (mean age 70 y), 196 were treated with LAAC, 318 with LABA, and 82 were treated with a combination. The overall incidence of stroke (8.53%) significantly increased in the combination group compared with LAAC (2.04%) or LABA (1.26%) only. In the Cox regression analysis, the adjusted hazard ratio over the 11-year survey period for stroke in patients treated with the combination compared with LABA only was 1.04 (95% confidence interval, 1.06-2.99) and for LAAC, it was 0.31 (95% confidence interval, 0.02-2.32).This cohort study using a large health insurance database showed that treating patients with COPD, with a combination of LAAC and LABA, may be associated with an increased hazard of stroke compared with treatment with either agent alone. We should be particularly cautious about comedication of LAAC and LABA in patients with COPD.
authors.affiliation: From the Department of Neurology, China Medical University Hospital (M-JT); School of Medicine, Medical College, China Medical University, Taichung (M-JT); Department of Neurology, China Medical University An-Nan Hospital, Tainan (M-JT); Department of Pharmacy, Kaohsiung Medical University Hospital (C-YC, Y-BH); School of Pharmacy, Master Program in Clinical Pharmacy, Kaohsiung Medical University, Kaohsiung (C-YC, Y-BH, P-CL, Y-HT); Department of Pharmacy, Chi Mei Medical Center, Tainan (H-CC); Department of Respiratory Therapy, Kaohsiung Medical University, Kaohsiung (C-JY); and Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC (P-CL).
authors.forename: Ming-Jun
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Yaw-Bin
authors.initials: YB
authors.lastname: Huang
authors.forename: Hsiao-Chung
authors.initials: HC
authors.lastname: Chao
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Yang
authors.forename: Pei-Chin
authors.initials: PC
authors.lastname: Lin
authors.forename: Yi-Hung
authors.initials: YH
authors.lastname: Tsai
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000069502:Budesonide, Formoterol Fumarate Drug Combination / Q000008:administration & dosage / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005260:Female; D000068297:Fluticasone-Salmeterol Drug Combination / Q000008:administration & dosage / Q000009:adverse effects; D000068759:Formoterol Fumarate / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D000068299:Salmeterol Xinafoate / Q000008:administration & dosage / Q000009:adverse effects; D020521:Stroke / Q000139:chemically induced; D013624:Taiwan / Q000453:epidemiology; D000069447:Tiotropium Bromide / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D000069502:Budesonide, Formoterol Fumarate Drug Combination; D018680:Cholinergic Antagonists; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D000068297:Fluticasone-Salmeterol Drug Combination; D000068299:Salmeterol Xinafoate; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide