Prevention and treatment of venous thromboembolism in hospital and the community: a research programme including the ExACT RCT
Fitzmaurice D., Fletcher K., Greenfield S., Jowett S., Ward A., Heneghan C., Knight E., Gardiner C., Roalfe A., Sun Y., Hardy P., McCahon D., Heritage G., Shackleford H., Hobbs FDR.
BACKGROUND:Deep-vein thrombosis and pulmonary embolism, collectively known as venous thromboembolism when clots are formed in the venous circulation, are common disorders that are often unprovoked (i.e. there is no obvious reason for the clot occurring). Some people, after having an unprovoked clot, are at a high risk of developing another, or at risk of developing a secondary clot, most importantly in the lungs. Furthermore, in the long term, some patients will develop circulation problems known as post-thrombotic syndrome. The aim of this programme was to improve the understanding of both the prevention and the treatment of thrombosis in people at the highest risk of recurrence. OBJECTIVES:To clarify if it is possible to identify those people at the highest risk of having a recurrent venous thromboembolism, and if it is possible to prevent this happening by giving anticoagulation treatment for longer. To clarify if it is possible to identify those people at the highest risk of developing post-thrombotic syndrome. To document the current knowledge level about prevention and treatment of venous thromboembolism. To find what the barriers are to implementing measures to prevent venous thromboembolism. To find the most cost-effective means of treating venous thromboembolism. DESIGN:Mixed methods, comprising a randomised controlled trial, qualitative studies, cost-effectiveness analyses and questionnaire studies, including patient preferences. SETTING:UK general practices and hospitals, predominantly from the Midlands and Shropshire. PARTICIPANTS:Adults attending participating anticoagulation clinics with a diagnosis of first unprovoked deep-vein thrombosis or pulmonary embolism, and health-care professionals, patients and other stakeholders who were involved in the prevention and treatment of venous thromboembolism. INTERVENTION:Extended treatment with oral anticoagulation therapy (2 years) versus standard care (treatment with oral anticoagulation therapy for at least 3 months). RESULTS:Work package 1 demonstrated that extended anticoagulation for up to 2 years was clinically effective and cost-effective in reducing the incidence of recurrent venous thromboembolism, with a small increase in the risk of bleeding. There was no difference in post-thrombotic syndrome incidence or severity, or quality of life, between those undergoing the extended treatment and those receiving the standard care. Work package 2 identified five common themes with regard to the prevention of hospital-acquired thrombosis: communication, knowledge, role of primary care, education and training, and barriers to patient adherence. Work package 3 suggested that extended anticoagulation with novel oral anticoagulants was cost-effective only at the £20,000-per-quality-adjusted life-year level for a recurrence rate of between 17.5% and 22.5%, depending on drug acquisition costs, while identifying a strong patient preference for extended anticoagulation based on a fear of recurrent venous thromboembolism. LIMITATIONS:The major limitation was the failure to reach the planned recruitment target for work package 1. CONCLUSIONS:Extended anticoagulation with warfarin for a first unprovoked venous thromboembolism is clinically effective and cost-effective and is strongly preferred by patients to the alternative of not having treatment. There are significant barriers to the implementation of preventative measures for hospital-acquired thrombosis. Further research is required on identifying patients in whom it is safe to discontinue anticoagulation, and at what time point following a first unprovoked venous thromboembolism this should be done. TRIAL REGISTRATION:Current Controlled Trials ISRCTN73819751 and EudraCT 2101-022119-20. FUNDING:This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 8, No. 5. See the NIHR Journals Library website for further project information.