Prediction models for recurrence and bleeding in patients with venous thromboembolism: A systematic review and critical appraisal

Abstract

INTRODUCTION: Prediction models for recurrence and bleeding are infrequently used when deciding on anticoagulant treatment duration after venous thromboembolism (VTE) due to concerns about performance and validity. Our aim was to critically appraise these models by systematically summarizing data from derivation and validation studies. MATERIALS AND METHODS: MEDLINE and CENTRAL were searched until November 15th, 2019. Studies on prediction models for recurrence or bleeding after at least 3 months of anticoagulation in adult patients with VTE were included. The PROBAST, ROBINS-I and RoB2 tools were used to assess risk of bias and applicability. RESULTS: Selection yielded 18 studies evaluating 8 models for recurrence (7 on development; 9 on validation; 1 update). Generally, models for recurrent VTE appeared to perform poorly to moderately in external validation studies (C-statistics 0.39-0.66, one 0.83). However, impact studies show that HERDOO2 and Vienna prediction model may identify patients with unprovoked VTE at low recurrence risk. Sixteen studies evaluating 14 models for anticoagulation-related bleeding were identified (7 on development; 9 on validation). Although some models seemed promising in development studies, their predictive performance was poor to moderate in external validation (C-statistics 0.52-0.71). All but 3 studies were considered at high risk of bias, mainly due to limitations in the statistical analysis. CONCLUSIONS: Prognostic models for recurrence and anticoagulation-related bleeding risk often have important methodological limitations and insufficient predictive accuracy. These findings do not support their use in clinical practice to weigh risks of recurrence and bleeding when deciding on continuing anticoagulation after initial treatment of VTE.