Risk of Fatal Bleeding in Episodes of Major Bleeding with New Oral Anticoagulants and Vitamin K Antagonists: A Systematic Review and Meta-Analysis

Abstract

BackgroundThe reversibility of new/novel oral anticoagulants (NOAC) is not well understood, whereas the reversal strategies for bleeding associated with vitamin k antagonists (VKA), such as warfarin, is well established. It is unknown whether outcomes are different between bleeds occurring with NOAC compared to VKA use.ObjectivesThis systematic review and meta-analysis of randomized controlled trials determines the relative odds of fatal bleeding given that a patient suffered a major bleed while on NOAC versus VKA therapy.Search MethodsData on major and fatal bleeding events was sought from randomized controlled trials of NOAC agents compared to VKAs.Main Results20 trials were included in the meta-analysis. From which, 4056 first-time, major bleeding events were reported and included in the primary analysis. The summary odds ratio for the conditional odds of fatal bleeding given that a major bleeding event occurred was 0.65 [0.52, 0.81] favoring the NOAC agents (p = 0.0001). The reduced odds of fatal bleeding with NOACs was not demonstrated after controlling for bleeding location. Given that an intracranial bleeding event occurred, the summary odds ratio for the conditional odds of fatal bleeding was 0.96 [0.70, 1.32]. For extracranial bleeding events, the summary odds ratio was also statistically insignificant at 0.945 [0.66, 1.35].Author’s ConclusionsThe odds ratio calculated in this meta-analysis showed a reduced odds of death in major bleeding associated with NOAC use. This risk reduction was due to a disproportionate amount of intracranial bleeding in the VKA arms. For any given bleeding site, there was no evidence of a significant difference in fatal outcomes from bleeds associated with NOAC versus VKA use.Protocol RegistrationProtocol registered on PROSPERO under CRD42014013294.

Acute Management of Anticoagulation-Associated Intracerebral Hemorrhage

“…The presumed largest relative increase in the incidence rate is evident in patients who have already suffered an ICH and are treated with anticoagulants due to the high risk of thromboembolism. For this patient cohort, the weight of evidence is not optimal, although possible incidence rates of up to 10 % per year are assumed [10,15,[24][25][26][27][28].…”

Extended Therapy of Venous Thrombosis by Oral Anticoagulants: Focus at Safety

“…Последующие мета-анализы показали, что группа НОАК характеризуется пониженным риском развития больших кровотечений по сравнению с АВК, в особенности при терапии ВТЭО [19]. Аналогичное преимущество было продемонстрировано в отношении риска развития внутричерепных кровоизлия-ний и летальных кровотечений [20,21].…”

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism – still a challenging issue

“…The observed low incidence of fatal bleeding was mainly due to the decrease of intracranial bleeds. It has been speculated that the warfarin role in provoking intracranial bleeding could rely on the ability to inhibit factor VIIa that is lost in the more selective DOAC [53,54,55].…”