Major bleeding risk associated with oral anticoagulant in real clinical practice. A multicentre 3-year period population-based prospective cohort study.

AIMS: The objective was to compare major bleeding risk of DOACs (per type and dose) with VKAs, irrespective of indication, using real-world data. METHODS: A population-based prospective cohort study, using the French national health data system (SNIIRAM), identified 47,469 adults living within five well-defined geographical areas, who were new users of oral anticoagulants in the period 2013-2015: 20,205 VKA users, 19,579 rivaroxaban users, 4,225 dabigatran users and 3,460 apixaban users. From all emergency departments within these areas, clinical data for all adults referred for bleeding was collected and medically validated. The databases were linked for common key variables. The main outcome measure was major bleeding: intracranial haemorrhage, major gastrointestinal bleeding and other major bleeding events. Hazard ratios were derived from adjusted Cox proportional hazard models. We used propensity score weighting as a sensitivity analysis, with separate analyses according to indications (atrial fibrillation or venous thromboembolism). RESULTS: Compared to VKAs, high and low-dose DOACs were associated with a reduced risk of intracranial haemorrhage (adjusted hazard ratio 0.55, 95% confidence interval 0.37 to 0.82 and 0.54, 0.26 to 1.12 respectively), and a reduced risk of other major bleeding events (0.41, 0.29 to 0.58 and 0.41, 0.22 to 0.79 respectively), irrespective of duration and indication. Neither DOAC dose evidenced any significant difference from VKAs in terms of risk of major gastrointestinal bleeding. CONCLUSIONS: There is a clear benefit of using DOACs with regard to intracranial haemorrhage. The study provides new insight into major gastrointestinal and other major bleeding events.