• Yaa-Hui Dong, Chia-Hsuin Chang, Joshua J Gagne, Chia-Lin Hsu, and Mei-Shu Lai.
• Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
• Pharmacotherapy. 2016 Jan 1; 36 (1): 26-37.

Study ObjectiveInhaled 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.DesignRetrospective cohort study.SettingsA population-based health care database from Taiwan.PatientsIndividuals 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.Measurements And Main ResultsWe 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).ConclusionsOur 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.© 2016 Pharmacotherapy Publications, Inc.

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