Journal of Neurology

, Volume 262, Issue 3, pp 516–522

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

  • Daniel Caldeira
  • Márcio Barra
  • Fausto J. Pinto
  • Joaquim J. Ferreira
  • João Costa
Review

DOI: 10.1007/s00415-014-7462-0

Cite this article as:
Caldeira, D., Barra, M., Pinto, F.J. et al. J Neurol (2015) 262: 516. doi:10.1007/s00415-014-7462-0

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 I2 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; I2 = 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; I2 = 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; I2 = 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.

Keywords

Intracranial hemorrhagesAnticoagulantsMeta-analysis

Supplementary material

415_2014_7462_MOESM1_ESM.tif (164 kb)
Supplementary Fig. 1: Flowchart of studies selection (TIFF 163 kb)
415_2014_7462_MOESM2_ESM.tif (455 kb)
Supplementary Fig. 2: Risk of bias table (TIFF 454 kb)
415_2014_7462_MOESM3_ESM.tif (85 kb)
Supplementary Fig. 3: Funnel plot of included studies (TIFF 85 kb)
415_2014_7462_MOESM4_ESM.pdf (198 kb)
Supplementary Table 1: Characteristics of included studies (PDF 197 kb)
415_2014_7462_MOESM5_ESM.pdf (124 kb)
Supplementary material 5 (PDF 124 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Daniel Caldeira
    • 1
    • 2
    • 3
  • Márcio Barra
    • 2
  • Fausto J. Pinto
    • 4
  • Joaquim J. Ferreira
    • 1
    • 2
  • João Costa
    • 1
    • 2
    • 5
    • 6
  1. 1.Clinical Pharmacology UnitInstituto de Medicina MolecularLisbonPortugal
  2. 2.Laboratory of Clinical Pharmacology and Therapeutics, Faculty of MedicineUniversity of LisbonLisbonPortugal
  3. 3.Cardiology DepartmentHospital Garcia de OrtaAlmadaPortugal
  4. 4.Cardiology Department, CCUL, CAML, Faculty of MedicineLisbonPortugal
  5. 5.Evidence Based Medicine Centre, Faculty of MedicineUniversity of LisbonLisbonPortugal
  6. 6.Portuguese Collaborating Centre of the Cochrane Iberoamerican Network, Faculty of MedicineUniversity of LisbonLisbonPortugal