Intracranial hemorrhage risk with the new oral anticoagulants: a systematic review and meta-analysis

Abstract

The new oral anticoagulants/non-vitamin K antagonists oral anticoagulants (NOACs) have recently reached the market and less is known about their safety in comparison to their efficacy. Therefore, we aimed to evaluate intracranial hemorrhage (ICH) risk with NOACs, the most feared adverse event of anticoagulation treatment. This is a systematic review and meta-analysis of phase III randomized controlled trials (RCTs) comparing NOACs versus any control and reporting ICH events. Studies were searched through Medline and Cochrane Library (April 2014). Reviews and reference lists were also screened. Random effects' meta-analysis was performed to derive pooled estimates expressed as relative risk (RR) and 95 % CI. Number needed to treat/harm (NNT/NNH) taking into account the baseline risk was also calculated. Heterogeneity was evaluated with I (2) test. 18 RCTs evaluating 148,149 patients were included. NOAC significantly reduced ICH risk compared to vitamin K antagonists (VKA) (RR 0.44; 95 % CI 0.36-0.54; I (2) = 37 %; NNT: 137 during 2 years) and to sequential treatment with low molecular weight heparin and VKA (RR 0.28; 95 % CI 0.12-0.65; I (2) = 0 %; NNT: 463 patients during 7 months). Compared to placebo, NOACs were associated with an increased ICH risk (RR 3.31; 95 % CI 1.59-6.90; I (2) = 0 %; NNH: 433 during 1 year). Results were similar for the different NOAC drugs and across the different clinical conditions. In patients requiring anticoagulation treatment, the risk of ICH is about half with the NOACs in comparison to standard antithrombotic treatment. This safer profile found in RCTs should be confirmed in real-world database studies.

Current knowledge on assessing the effects of and managing bleeding and urgent procedures with direct oral anticoagulants

“…1,2 The agents currently available include the direct thrombin inhibitor dabigatran and the direct factor Xa (FXa) inhibitors rivaroxaban, apixaban, and edoxaban. In general, observations from clinical trials and subsequent meta-analyses have suggested similar or lower major bleeding rates with the DOACs when compared with warfarin, [3][4][5][6][7] particularly for central nervous system (CNS) bleeding events. 8 One exception may be gastrointestinal bleeding events, as higher rates have been observed in patients receiving DOACs when com- …”

Non-vitamin K antagonist oral anticoagulants in the cardioversion of patients with atrial fibrillation: systematic review and meta-analysis

“…In contrast to VKAs, NOACs have a lower risk of major bleeding events such as intracranial hemorrhage [4], a faster onset of action, a predictable dose-response relationship, and does not require frequent anticoagulation intensity evaluation, similar to INR testing in patients treated with VKA [5]. Different from ximelagatran (an oral anti-IIa inhibitor withdrawn due to the high risk of liver injury), recent NOACs did not show increased risk of drug-induced liver injury [6].…”

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].…”