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Risk of Severe Cardiovascular Events From Add-On Tiotropium in Chronic Obstructive Pulmonary Disease

      Abstract

      Objective

      To examine the risk of cardiovascular disease (CVD) from tiotropium added to inhaled long-acting β2 agonists (LABAs) and inhaled corticosteroids (ICSs) in a nationwide population with chronic obstructive pulmonary disease (COPD).

      Patients and Methods

      This nested case-control study included 65,966 patients with COPD treated with LABAs and ICSs identified from the Taiwan nationwide health care claims database from January 1, 2007, through June 30, 2011. Cases were all patients with a first primary diagnosis of ischemic heart disease, heart failure, stroke, or arrhythmia from inpatient or emergency care settings during follow-up, and each was matched with 4 disease risk score–matched controls from risk sets. The use of tiotropium in the year before the index/event date was measured, stratified by duration since therapy initiation, concomitant COPD medications, and dosage form. Conditional logistic regression models were used to estimate odds ratios of the CVD risk from add-on tiotropium therapy.

      Results

      From the study cohort, with a mean age of 70.3 years (interquartile range, 61.8-79.4 years), 3188 CVD cases (incidence rate, 6.2 [95% CI, 6.0-6.4] cases per 100 person-years) and 12,349 matched controls were identified. The new use of tiotropium was associated with a 1.88-fold (95% CI, 1.44-2.46) increased CVD risk within 30 days of therapy initiation, and the association was sustained up to 60 days after treatment initiation (adjusted odds ratio, 1.71; 95% CI, 1.08-2.70). The risk persisted across all tiotropium regimens, with a case-crossover analysis, and in comparison with new add-on theophylline therapy.

      Conclusion

      Tiotropium newly added to LABA/ICS combination therapy was associated with an increased cardiovascular risk in patients with COPD.

      Abbreviations and acronyms:

      COPD (chronic obstructive pulmonary disease), CVD (cardiovascular disease), DRS (disease risk score), ED (emergency department), ICD-9 (International Classification of Diseases, Ninth Edition), ICS (inhaled corticosteroid), LABA (long-acting β2 agonist), LAMA (long-acting antimuscarinic agent), NHI (National Health Insurance), NHIRD (National Health Insurance Research Database), OR (odds ratio), RCT (randomized controlled trial), SABA (short-acting β2 agonist)
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