Incidence of venous thromboembolism in patients with cancer – A cohort study using linked United Kingdom databases

doi:10.1016/j.ejca.2012.10.021

European Journal of Cancer

Volume 49, Issue 6, April 2013, Pages 1404-1413

https://doi.org/10.1016/j.ejca.2012.10.021 Get rights and content

Abstract

Background

Accurate population-based data are needed on the incidence of venous thromboembolism (VTE) in patients with different cancers in order to inform guidelines on which hospitalised and ambulatory cancer patients should receive VTE prophylaxis.

Methods

We conducted a cohort study using data from the Clinical Practice Research Datalink, linked to Hospital Episode Statistics, Cancer Registry data and Office for National Statistics cause of death data. We determined the incidence rates (cases per 1000 person–years) of VTE separately for 24 cancer sites. To determine relative risk, incidence rates were compared to frequency-matched controls (by age) with no record of cancer.

Findings

We identified 83,203 cancer patients and 577,207 controls. New cases of VTE were diagnosed in 3352 cancer patients, and 6353 controls. The absolute rate of VTE in all cancers was 13.9 per 1000 person–years (95% confidence interval [CI] 13.4–14.4), corresponding to an age, sex and calendar year adjusted hazard-ratio of 4.7 (CI 4.5–4.9) between cancer patients and the general population. Rates varied greatly by cancer site (range; 98 (CI 80–119) in pancreatic cancer to 3.1 (CI 1.5–6.5) in thyroid cancer), age (range; 16.9 for patients over 80 years to 4.9 for those under 30 years) and time from diagnosis (range; 75 in the first three months to 8.4, >1 year after diagnosis).

Interpretation

VTE is strongly linked to cancer, but the annual rate varies greatly by cancer site, proximity to diagnosis and age. Prophylaxis guidelines should take account of cancer site and such intervention should also be targeted towards the three months following diagnosis.

Introduction

It is long established that the risk of venous thromboembolism (VTE), which incorporates deep vein thrombosis (DVT) and pulmonary embolism (PE) is increased substantially in cancer patients, with 20% of VTE events occurring in people with cancer.¹ Cancer patients are also known to be at substantially higher risk of death if they have a concurrent VTE diagnosis.² Various factors are known to influence risk of VTE in cancer and non-cancer patients, including age, immobility, surgery and trauma.³ The reasons for the increase in incidence of VTE in cancer patients are myriad, but include pathophysiological changes occurring in cancer treatments and the decreased mobility often associated with cancer diagnosis.⁴

Current United Kingdom (UK) guidelines, published by the National Institute for Health and Clinical Excellence (NICE)⁵ indicate use of thromboprophylaxis in cancer patients with on-going cancer or cancer treatment, but only routinely to those with reduced mobility, and not ambulatory patients. United States (US) guidelines from the National Clinical Cancer Network (NCCN)⁶ are similar in their treatment of inpatients, but have a more detailed assessment of VTE risk factors and suggest that some outpatient chemotherapy patients could also benefit from prophylaxis. The recent American College of Chest Physicians guidelines have also recently changed to suggest thromboprophylaxis in outpatients at high risk of VTE.⁷ While general guidelines may be effective in some cases, potential variation in risk between different patient groups with cancer means that some patients in high risk groups may benefit from VTE prophylaxis while ambulant, whereas some at low risk may suffer net harm from prophylaxis and its associated adverse effects.

While a number of previous attempts have been made to characterise the risk of VTE in cancer in more detail,8, 9, 10, 11, 12 these are limited in the number of cancer types studied, the length of patient follow-up or their assessment of VTE. This study uses the recently linked UK Clinical Practice Research Datalink (CPRD), Hospital Episode Statistics (HES), National Cancer Intelligence Network Cancer Registry data and Office of National Statistics (ONS) death certificate data to provide a more comprehensive and accurate view of risk of VTE in a cancer population, in comparison with a control population.

Section snippets

Patients and data sources

We conducted a cohort study using linked data from four sources. The CPRD, formerly the General Practice Research Database, is a prospectively gathered, anonymised primary care database using data from more than 600 GP practices in the UK from 1987 onwards. It provides all recorded primary care data on patients including clinical diagnoses, treatments and outcomes. Its validity has been tested in numerous studies13, 14, 15, 16 and it is thought to represent the UK population well in terms of

Patients

83,203 patients were identified with cancer along with 577,207 controls. Median follow up time was 2.0 years (interquartile range (IQR) 118 days to 5.7 years) for cancer patients and 2.6 years (IQR 353 days to 5.7 years) for controls. Age was frequency matched in 25 year age categories, though differences in intra group age distribution meant the median age remained slightly higher in cancers (70 years versus 67 years in controls) (Table 1).

VTE incidence in all cancer patients

A total of 3352 cancer patients had a subsequent diagnosis of

Discussion

We found the rate of VTE in people with cancer to be substantial in many cancer sites compared to the general population. Variations in rate due to differences in cancer site and proximity to cancer diagnosis meant estimates ranged from 0.8 per 1000 person years in patients with testicular cancer more than 12 months after diagnosis, to 183 in patients with a metastatic cancer of unknown primary, in the first 3 months after diagnosis. Many cancers, especially those occurring in the abdominal or

Role of the funding source

The funders (Cancer Research UK) had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Conflict of interest statement

The spouse of T.R.C. is an employee of Astrazeneca.

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Incidence of venous thromboembolism in patients with cancer – A cohort study using linked United Kingdom databases

Abstract

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Patients and data sources

Patients

VTE incidence in all cancer patients

Discussion

Role of the funding source

Conflict of interest statement

Chest

J Thromb Haemost

Lancet

Best Pract Res Clin Haematol

Surgery

Crit Rev Oncol Hematol

Eur J Cancer

Am J Med

Best Pract Res Clin Haematol

Ann Thorac Surg

Blood

Blood

Blood

Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study

Arch Intern Med

Prognosis of cancers associated with venous thromboembolism

N Engl J Med

Risk factors for venous thromboembolism

Circulation

Assessing risk of venous thromboembolism in the patient with cancer

J Clin Oncol

Venous thromboembolic disease

J Natl Compr Canc Netw

Malignancies, Prothrombotic mutations, and the risk of venous thrombosis

JAMA

Incidence of venous thromboembolism and its effect on survival among patients with common cancers

Arch Intern Med