Risk of Recurrent Venous Thrombosis: A Validation Study of the Vienna Prediction Model

Venous thromboembolism (VTE) is a common disease with an incidence of 12/1000 persons per year. VTE is a chronic disease with a considerable risk of recurrence. Patients with unprovoked VTE, i.e. VTE in the absence of a temporary risk factor including surgery, cancer or immobilisation, have a recurrence risk as high as 30% within 5 years after stopping anticoagulation with a case-fatality of recurrence between 3.6%-10%. According to recent guidelines, indefinite anticoagulation is recommended in these patients. However, anticoagulation confers a considerable bleeding risk with an incidence of fatal bleedings of 0.10.5% per year. It is therefore of utmost clinical importance to identify those patients, who will not benefit from indefinite anticoagulation, i.e. patients, in whom the bleeding risk during anticoagulation is higher than the recurrence risk. Several attempts to discriminate high and low risk patients such as screening for acquired and inherited risk factors of recurrence or measurement of coagulation activation markers have either failed (thrombophilia screening) or were only moderately successful (stratification according to D-Dimer only). We developed a scoring model (Vienna Prediction Model, Eichinger et al, Circulation 2010), which can be used to stratify patients with unprovoked VTE according to their recurrence risk based on 3 parameters: sex, location of VTE and D-Dimer measured 3 weeks after stopping anticoagulation. This prediction model is simple to use also by general practitioners and in daily routine care as it requires only easily obtainable clinical data and a widely available inexpensive laboratory assay. Before implementation of this model into routine clinical practice an independent prospective validation is required which is the rationale of this study: to test the hypothesis that patients with a first unprovoked VTE who score low in our model will not benefit from indefinite anticoagulation because the risk of bleeding will outweigh the recurrence risk. In these patients anticoagulation will be discontinued after 3-6 months and the recurrence risk will be calculated by use of the Vienna Prediction Model 3 weeks thereafter. Low risk patients defined by a score of equal or less than 180 (which corresponds to a recurrence rate of 4.4% at 1 year and 17.7% at 5 years) comprise 60% of our study population and will be included and will be left untreated. Patients with a score of more than 180 will not be included and their management will follow current guidelines and will be left at the discretion of the treating physician. Follow-up will be two years and the endpoint will be objectively diagnosed recurrent symptomatic VTE. To ensure the inclusion of a sufficient number of patients in a limited period of time the study will be performed nation wide with participation of most thrombosis centers across the country.

Venous thromboembolism (VTE) is a common disease (12/1000 persons per year). VTE is a chronic disease as it tends to recur. Patients with unprovoked VTE have a particularly high recurrence risk (up to 10%/year), and international experts recommend long-term anticoagulation to all these patients. However, the risk of recurrent VTE varies considerably. Many patients will stay recurrence free but are exposed to an unnecessary bleeding risk if these guidelines are applied. It is therefore important to identify subgroups of patients with unprovoked VTE who have a low recurrence risk and in whom it is safe to stop anticoagulant therapy. We developed a risk assessment model (Vienna Prediction Model, VPM), which can be used to classify patients with a first unprovoked VTE according to their recurrence risk by combining sex, location of VTE and D-Dimer. In a systematic review of all available studies the VPM was rated as the most promising because of its strong development methodology, its applicability and because results from external validation are already available. With the support of the Austrian Science Fund (KLIF 316) we initiated in 2014 a cohort management study (VALID study) in order to externally and prospectively validate the VPM. In patients with a first unprovoked VTE anticoagulation is discontinued after 3-7 months and the recurrence risk is calculated by use of the VPM. Low risk patients are included in the study and do not receive further anticoagulant treatment. Patients with a high risk are not included in the study and their management is left to the discretion of the treating physician. Follow-up is two years and the endpoint is objectively diagnosed recurrent symptomatic VTE. The performance of the study as regards patient recruitment, number of participating centers, number of losses to follow-up, and requirement to keep within recurrence rate boundaries is excellent. The study has been performed under stringent financial considerations. Currently, about 600 of the foreseen 800 patients have been recruited. We will continue recruitment for proper prospective validation of the VPM, to complete follow-up of all patients, and to analyse the data and present the findings. At present, all patients with an unprovoked VTE shall receive long-term anticoagulation which presents a burden to the patient (bleeding risk, psychologic) and to the healthcare system. It is the ultimate goal to discriminate between patients with an unprovoked VTE in need of long-term thromboprophylaxis from those in whom a short course of anticoagulation is sufficient.