Optimale duur van secundaire preventie door orale toediening van vitamine K-antagonisten na diep veneuze trombose of longembolie
03 / 2000 - 06 / 2004
Om een recidief van diepveneuze trombose te voorkomen, is behandeling met laag-moleculair-gewicht-heparine veiliger en effectiever dan met ongefractioneerde heparine, concludeert Carlo van Dongen na literatuurstudie. De dosis kan evengoed eenmaal per dag worden gegeven als tweemaal per dag. Na de initiële behandeling met heparine krijgen de patiënten nog enkele maanden vitamine-K-antagonisten. Van Dongen ontwikkelde een beslismodel om de optimale duur van die therapie vast te stellen. Daarin worden niet alleen de medische voor- en nadelen afgewogen, maar wordt ook het oordeel van de patiënt over de behandeling meegenomen.
The usual duration of secondary prevention with oral anticoagulant for recurrent venous thromboembolism in patients with a venous thromboembolic event is 3 months. Recently some publications indicated that prolonged anticoagulation is very effective to prevent recurrent thromboembolism (relative risk reductions varying around 90%). On the basis of a recent meta-analysis, the fatality rate of bleeding appears greater than the fatality rate of recurrent venous thromboembolic events. Also, there are strong indications that the risk of clinically relevant bleeding increases importantly with age. Finally, there is convincing evidence that the risk of recurrent venous thromboembolism depends on the type of initial thrombosis (preceded by a temporary risk factor or different) and decreases over time. When these data are combined, it does not seem adequate to reduce the treatment for every patient to 3 months. However, extending the duration of treatment to 12 months or longer for every patient could lead to disadvantages (for elderly patients) or marginal effects for patients for 40 to 60 years. A major problem with the interpretation of the clinical trial data and the decision analysis is the inadequate knowledge of the utility of the different non-fatal complications (such as bleeds, recurrent thromboembolic events, post-thrombotic syndrome) and the burden of treatment. The current project is aimed at measuring the utilities of non-fatal complications and the burden of treatment itself. A systematic literature review will be conducted to establish the baseline risk for various groups of patients and the efficacy of vitamin K antagonists in relation to time since the thromboembolic event. These data will be combined, using a decision analytic approach, to define an optimal duration of secondary prevention with vitamin K antagonists, based on the characteristics of the individual patient with venous thromboembolism. [Objectives]: The main objective of this project is to define the optimal duration of secondary prevention of recurrent venous thromboembolism with oral vitamin K antagonists in patients with a venous thromboembolic event. This objective is achieved in three steps: Firstly, the risk of recurrent venous thromboembolic event after the usual duration of secondary prevention with oral anticoagulants of 3 months in relation to the patient characteristics and time since event will be assessed, based on a literature review. In addition, the efficacy of oral anticoagulant upon continuation and the risk of bleeding in relation to age will be obtained using a literature review. Secondly, quality of life will be assessed using standard scales and standardized interviews conducted among patients with venous thromboembolic disease with and without non-fatal complications to assess the utilities of these heath states. Finally, this information will be combined in a multi-state decision analytic model. [Relevance for cardiovascular diseases]: This project aims to optimize the use of resources for secondary prevention of thrombotic complications, taking into account both the effects on quality of life of the efficacy and safety aspects of treatment with oral anticoagulants as well as the burden of treatment.