Comparative Cardiovascular and Cerebrovascular Safety of Inhaled Long-Acting Bronchodilators in Patients with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study.

STUDY 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.

DESIGN

Retrospective cohort study.

SETTINGS

A population-based health care database from Taiwan.

PATIENTS

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.

MEASUREMENTS AND MAIN 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.