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Reservations against new oral anticoagulants after stroke and cerebral bleeding.

Abstract
Dabigatran, rivaroxaban, and apixaban are the new oral anticoagulants (NOAC) which have been investigated in patients with atrial fibrillation (AF) for primary and secondary prevention of stroke and thromboembolism. In these trials NOAC had a similar efficacy and safety profile compared to traditional vitamin-K-antagonists such as warfarin. We advise caution in the use of NOAC in patients with stroke or cerebral hemorrhage because of the following reasons: 1) Patients with cerebral bleeding were excluded from the trials. 2) Stroke within 14 days and severe stroke within 6 months before screening were exclusion criteria in the trials investigating dabigatran and rivaroxaban. 3) There is no antidote for reversal and no reliable laboratory monitoring of the anticoagulant effect for emergency situations. 4) NOAC are either substrates of the P-glycoprotein (P-gp) or are metabolized by the cytochrome P450 (CYP) system, or both. Drug-drug interactions between NOAC and P-gp and CYP-affecting drugs are largely unknown. 5) Long-term effects of thrombin generation inhibition on the occurrence of infections, malignancies, dementia, and other diseases are unknown. Based on these considerations it is our opinion that studies of NOAC in patients with stroke compared with other prevention strategies, as well as more post marketing surveillance data, are required.
AuthorsClaudia Stöllberger, Josef Finsterer
JournalJournal of the neurological sciences (J Neurol Sci) Vol. 330 Issue 1-2 Pg. 16-7 (Jul 15 2013) ISSN: 1878-5883 [Electronic] Netherlands
PMID23628464 (Publication Type: Journal Article)
CopyrightCopyright © 2013 Elsevier B.V. All rights reserved.
Chemical References
  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Vitamin K
  • Thrombin
Topics
  • Animals
  • Anticoagulants (adverse effects, therapeutic use)
  • Humans
  • International Normalized Ratio
  • Intracranial Hemorrhages (complications)
  • Platelet Aggregation Inhibitors (adverse effects, therapeutic use)
  • Stroke (complications, prevention & control)
  • Thrombin (biosynthesis)
  • Vitamin K (antagonists & inhibitors)

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