Effects of tiotropium on the risk of coronary heart disease in patients with COPD: a nationwide cohort study

Inhaled long-acting muscarinic antagonist (LAMA) is recommended for the treatment of chronic obstructive pulmonary disease (COPD). However, there is still concern that LAMA may cause cardiovascular adverse events in COPD patients. Therefore, this study aimed to determine whether the administration of tiotropium, the first commercially available LAMA, could increase the risk of coronary heart disease (CHD) in COPD patients through a nationwide cohort study. We used the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) database between 2002 and 2014 for the analysis. We applied a washout period of COPD diagnosis during 2002–2003 and excluded the patients who used an inhaler before the diagnosis of COPD. We also excluded patients who were diagnosed with CHD before inhaler use. Among a total of 5787 COPD patients, 1074 patients were diagnosed with CHD. In the Cox regression models with time-dependent tiotropium usage, we found that tiotropium significantly increased the risk of CHD in a subgroup of age [Formula: see text] 55 years compared to non-users of tiotropium (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [CI], 1.003–1.54). When analyzed by dividing into tertiles (high/middle/low) according to the cumulative tiotropium exposure, the high tertile exposure group of tiotropium was associated with a higher risk of CHD compared with the low tertile exposure group of tiotropium. Additionally, the risk of CHD was higher in the high tertile exposure group of tiotropium in the age 55 and older group and in the never smoker group. When prescribing tiotropium for COPD patients, particularly those over 55 years of age and never-smokers, it is desirable to evaluate the risk of CHD in advance and closely follow-up for CHD occurrence.