Prediction of significant bleeding during vitamin K antagonist treatment for venous thromboembolism in outpatients

Summary Bleeding is the most concerning complication associated with anticoagulant therapy but poorly characterized and important for risk/benefit assessment. We developed a risk stratification score to predict vitamin K antagonist (VKA)‐associated bleeding in venous thromboembolism (VTE) using the UK Clinical Practice Research Datalink. Significant bleeding events in outpatients consisted of major bleeding and clinically relevant non‐major bleeding requiring hospitalisation (CRNMB‐H) within 90 days of VKA initiation. A scoring scheme for predicting bleeding was developed from subhazard ratios, validated using cross‐validation and expressed by the C‐statistic. The study cohort consisted of 10,010 patients with first VTE receiving initial VKA treatment, mean age 62·2 years. Between 2008 and 2016, 167 significant bleeding events were recorded (1·7%), i.e. incidence rate was 7·4/100 person‐years. Independent predictors for community‐acquired significant bleeding included active cancer, trauma/surgical procedure, male gender, dementia, liver disease, anaemia, history of bleeding, cerebrovascular, renal and chronic pulmonary disease, VTE presenting as pulmonary embolism and age over 75. The overall C‐statistic was 0·68 (95% CI, 0·60–0·76), 0·75 (0·60–0·88) for major bleeding and 0·65 (0·55–0·75) for CRNMB‐H, and higher than in other risk schemes applied to our study population. The developed risk score may identify patients having a significant bleeding risk, in particular major bleeding events, in outpatients.