Elsevier

The Lancet

Volume 375, Issue 9715, 20–26 February 2010, Pages 657-663
The Lancet

Articles
Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study

https://doi.org/10.1016/S0140-6736(09)61963-2Get rights and content

Summary

Background

Patients with inflammatory bowel disease who develop deep vein thrombosis or pulmonary embolism often have active disease at the time of thromboembolism. We therefore aimed to quantify the risk of venous thromboembolism prospectively during different activity phases of inflammatory bowel disease.

Methods

From the General Practice Research Database, we matched patients with prospectively recorded inflammatory bowel disease from November, 1987, until July, 2001 with up to five controls by age, sex, and general practice. A flare was defined as the period 120 days after a new corticosteroid prescription. We used Cox regression analysis with time-varying covariates to accommodate changes in the state of inflammatory bowel disease, and whether patients were at high risk of venous thromboembolism after hospitalisation.

Findings

13 756 patients with inflammatory bowel disease and 71 672 matched controls were included in the analysis, and of these 139 patients and 165 controls developed venous thromboembolism. Overall, patients with inflammatory bowel disease had a higher risk of venous thromboembolism than did controls (hazard ratio 3·4, 95% CI 2·7–4·3; p<0·0001; absolute risk 2·6 per 1000 per person-years). At the time of a flare, however, this increase in risk was much more prominent (8·4, 5·5–12·8; p<0·0001; 9·0 per 1000 person-years). This relative risk at the time of a flare was higher during non-hospitalised periods (15·8, 9·8–25·5; p<0·0001; 6·4 per 1000 person-years) than during hospitalised periods (3·2, 1·7–6·3; p=0·0006; 37·5 per 1000 person-years).

Interpretation

Trials of primary prophylaxis of venous thromboembolism are warranted to find out whether this important complication can be prevented.

Funding

National Association for Colitis and Crohn's Disease.

Introduction

Venous thromboembolism in the leg is associated with a short-term mortality rate of about 6%, whereas the rate after embolism in the pulmonary circulation is as high as 20%.1, 2, 3, 4 Infection5 and inflammation are thought to predispose to this life-threatening disease, and people with inflammatory bowel disease seem to be particularly at risk.6 Research suggests that most patients with inflammatory bowel disease have active disease at the time of developing venous thromboembolism.7, 8 The three-fold overall increase in risk9 has led to the use of thromboprophylaxis as the standard of care for patients with active inflammatory bowel disease admitted to hospital. However, the absolute and relative risks in people with active disease who are not admitted to hospital are not known. Such information is important because much less than 50% of venous thromboembolisms arising in inflammatory bowel disease occur in patients who have been hospitalised within the past 3 months.10 If ambulant patients also have an increased risk then optimum avoidance of this disease cannot be achieved without consideration of outpatients. Active inflammatory bowel disease might need to be taken into consideration in the design of clinical models to identify high-risk groups of patients that presently include only a few pre-existing morbidities (including active cancer).11, 12

Although risk of venous thromboembolism increases for a short period after some events (such as admission to hospital,13 long-haul flight,14, 15 or hip fracture4), little is known about how these interact with each other except that some groups of inpatients are at high risk. If we can identify individuals with inflammatory bowel disease at high risk of venous thromboembolism when they are outpatients, then results from thromboprophylaxis in inpatients suggest that much of the associated morbidity and mortality might be preventable.16, 17 Our aim was therefore to assess different potentially interacting periods to separate out the effects of hospital admission and active inflammatory bowel disease on the risk of venous thromboembolism.

Section snippets

Study population

The General Practice Research Database (GPRD) is a large longitudinal UK database that was established in 1987 and contains the anonymised primary-care records of more 8 million patients. Data are audited to ensure at least 95% of medical events and prescriptions are satisfactorily recorded, and have been shown to provide results consistent with other data sources in the UK. The validity of diagnoses of inflammatory bowel disease (and its flares) and venous thromboembolism within this dataset

Results

13 756 patients with inflammatory bowel disease and 71 672 matched controls met our inclusion criteria (table 1). Individuals with inflammatory bowel disease were less likely to be smokers, had a lower mean body-mass index, but were more likely to have a diagnosis of cancer (before or during the study), and have a history of venous thromboembolism than were controls (all p<0·0001). Patients with inflammatory bowel disease contributed a total of 53 535 person-years to the analysis (mean 3·9

Discussion

Inflammatory bowel disease was associated with a roughly three-fold increase in the risk of venous thromboembolism. Compared with the general population while ambulatory, the risk of venous thromboembolism was increased about 16-fold for non-hospitalised patients with active inflammatory bowel disease. Despite the low absolute risks during non-hospitalised periods, these results suggest that active inflammatory bowel disease in ambulatory patients might be a far greater risk factor for venous

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