Anti-thrombotic therapy in patients with atrial fibrillation and intracranial hemorrhage

Abstract

Patients with atrial fibrillation have an increased risk of ischemic stroke that can be dramatically lowered by treatment with anticoagulants. The annual rate of major bleeds with warfarin averages about 2%. The rates of intracerebral and intracranial bleeds are significantly reduced with the use of the novel direct oral anticoagulants (DOACs) compared with warfarin. Treatment of anticoagulation-related intracerebral hemorrhage is based on the results of case series and small trials. Resumption of anticoagulation in patients with atrial fibrillation who had an intracerebral bleed depends on the etiology and location of the bleeding and the absolute rate of stroke in the absence of anticoagulation.

Keywords::

• atrial fibrillation
• cerebral hemorrhage
• direct oral anticoagulants
• intracranial hemorrhage
• meta-analysis
• randomized trial
• stroke
• warfarin

Acknowledgements

The authors wish to thank R Hart, Population Health Research Institute/McMaster University David Braley Cardiac, Vascular and Stroke Research Institute (DBCVSRI), London, Ontario, Canada for his critical comments.

Financial & competing interests disclosure

HC Diener received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Abbott, Allergan, AstraZeneca, Bayer Vital, BMS, Boehringer Ingelheim, CoAxia, Corimmun, Covidien, Daichii-Sankyo, D-Pharm, EV3, Fresenius, GlaxoSmithKline, Janssen Cilag, Johnson & Johnson, Knoll, Lilly, MSD, Medtronic, MindFrame, Neurobiological Technologies, Novartis, Novo-Nordisk, Paion, Parke-Davis, Pfizer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, Thrombogenics, WebMD Global, Wyeth and Yamanouchi. Financial support for research projects was provided by Astra/Zeneca, GSK, Boehringer Ingelheim, Lundbeck, Novartis, Janssen-Cilag, Sanofi-Aventis, Syngis and Talecris. A Bakhai participates in clinical trials and acts as a lecturer and advisor for scientific and economic matters for multiple pharma and device companies, to regional and national regulatory bodies and commercial research companies. R Veltkamp has received consulting honoraria, research support, travel grants and speakers’ honoraria from Bayer HealthCare, Boehringer Ingelheim, BMS Pfizer, Roche Diagnostics, CSL Behring, St. Jude Medical and Sanofi Aventis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Patients with atrial fibrillation have an increased risk of ischemic stroke, which can be lowered by treatment with anticoagulants with close monitoring.

• The annual rate of major bleeds with warfarin is around 2%.

• The rate of intracerebral and intracranial bleeds is significantly reduced with the use of the novel direct oral anticoagulants compared with warfarin.

• Treatment of anticoagulation related intracerebral hemorrhage is based on the results of case series and small trials. Randomized controlled trials are needed as well as large observational registries.

• Resumption of anticoagulation in patients with atrial fibrillation who have intracerebral bleeding depends on the etiology and location of the bleeding.