A three-year prospective study of the presentation and clinical outcomes of major bleeding episodes associated with oral anticoagulant use in the UK (ORANGE study)

Abstract

The outcomes of patients developing major bleeding while on oral anticoagulants remain largely unquantified. The objectives of this study were to: (i) describe the burden of major hemorrhage associated with all available oral anticoagulants in terms of proportion of bleeds which are intracranial hemorrhages, in-hospital mortality and duration of hospitalization following major bleeding; (ii) identify risk factors for mortality; and (iii) compare the characteristics of major hemorrhage between cases treated with warfarin and direct oral anticoagulants for the subgroups of patients with atrial fibrillation or venous thromboembolism. This was a multicenter, 3-year prospective cohort study of patients aged ≥18 years on oral anticoagulants who developed major hemorrhage leading to hospitalization. The patients were followed up for 30 days or until discharge or death, whichever occurred first. In total 2,192 patients (47% female, 81% on warfarin, median age 80 years) were reported between October 2013 and August 2016 from 32 hospitals in the UK. Bleeding sites were intracranial (44%), gastrointestinal (33%), and other (24%). The in-hospital mortality was 21% (95% CI: 19%-23%) overall, and 33% (95% CI: 30%-36%) for patients with intracranial hemorrhage. Intracranial hemorrhage, advanced age, spontaneous bleeding, liver failure and cancer were risk factors for death. Compared to warfarin-treated patients, patients treated with direct oral anticoagulants were older and had lower odds of subdural/epidural, subarachnoid and intracerebral bleeding. The mortality rate due to major bleeding was not different between patients being treated with warfarin or direct oral anticoagulants. Major bleeding while on oral anticoagulant therapy leads to considerable hospital stays and short-term mortality.

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

“…Gastrointestinal and intracranial bleeding were most commonly associated with mortality. The frequency of bleeding in the different sites was consistent with other recent studies (Green et al, 2018). We examined the first three months of anticoagulation with VKA because the risk of bleeding is highest over that time period, and particularly high in the first month (Kearon et al, 2016).…”

Major bleeding with antithrombotic agents: a 2012–2015 study using the French nationwide Health Insurance database linked to emergency department records within five areas – rationale and design of SACHA study

“…These criteria were anyway close to each other, and we considered that a fall in haemoglobin level of 20 g/L or more was a tricky criterion to estimate when recruiting in emergency rooms as the baseline haemoglobin level was not often available. These same criteria were used in other observational studies . Otherwise, considering indication bias when comparing VKA to NOAC, we plan a sensitivity analysis on ‘common’ indications.…”

“…Since 2014, several real‐world observational studies investigated the bleeding risk of NOAC in many countries . Annex 10 reports some characteristics of these postapproval published studies and shows heterogeneity for many aspects: most of them used retrospective data from nationwide administrative or insurance databases with limited clinical information – no access for patient's mortality .…”

“…Annex 10 reports some characteristics of these postapproval published studies and shows heterogeneity for many aspects: most of them used retrospective data from nationwide administrative or insurance databases with limited clinical information – no access for patient's mortality . Few studies were prospective . Medical validation of patient's bleeding events was scarce .…”

“…International multicentre trials have shown noninferiority to warfarin in patients with AF with lower risk of intracranial haemorrhage but a higher risk of gastrointestinal bleeding . Several reports from registries and analysis of claims databases have recently suggested, compared with VKA, a similar safety profile of NOAC in the community and in randomized trials. However, meta‐analyses highlighted inconsistency among those observational studies using different designs: Weeda et al.…”