COPD disease severity and the risk of venous thromboembolic events: a matched case–control study

BACKGROUND: It is generally accepted that people with chronic obstructive pulmonary disease (COPD) are at increased risk of vascular disease, including venous thromboembolism (VTE). While it is plausible that the risk of arterial and venous thrombotic events is greater still in certain subgroups of patients with COPD, such as those with more severe airflow limitation or more frequent exacerbations, these associations, in particular those between venous events and COPD severity or exacerbation frequency, remain largely untested in large population cohorts. METHODS: A total of 3,594 patients with COPD with a first VTE event recorded during January 1, 2004 to December 31, 2013, were identified from the Clinical Practice Research Datalink dataset and matched on age, sex, and general practitioner practice (1:3) to patients with COPD with no history of VTE (n=10,782). COPD severity was staged by degree of airflow limitation (ie, GOLD stage) and by COPD medication history. Frequent exacerbators were defined as patients with COPD with ≥ 2 exacerbations in the 12-month period prior to their VTE event (for cases) or their selection as a control (for controls). Conditional logistic regression was used to estimate the association between disease severity or exacerbation frequency and VTE. RESULTS: After additional adjustment for nonmatching confounders, including body mass index, smoking, and heart-related comorbidities, there was evidence for an association between increased disease severity and VTE when severity was measured either in terms of lung function impairment (odds ratio [OR](moderate:mild) =1.16; 95% confidence intervals [CIs] =1.03, 1.32) or medication usage (OR(severe:mild/moderate) =1.17; 95% CIs =1.06, 1.26). However, there was no evidence to suggest that frequent exacerbators were at greater risk of VTE compared with infrequent exacerbators (OR =1.06; 95% CIs =0.97, 1.15). CONCLUSION: COPD severity defined by airflow limitation or medication usage, but not exacerbation frequency, appears to be associated with VTE events in people with COPD. This finding highlights the disconnect between disease activity and severity in COPD.