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Balancing ischaemia and bleeding risks with novel oral anticoagulants

An Erratum to this article was published on 02 December 2014

This article has been updated

Key Points

  • Novel oral anticoagulants (NOACs) provide the greatest net clinical benefit in the management of patients with atrial fibrillation, followed by those with venous thromboembolism or acute coronary syndrome

  • In patients with atrial fibrillation, NOACs reduce the risk of intracranial haemorrhage compared with warfarin, but have more variable effects on gastrointestinal haemorrhage

  • In the treatment of venous thromboembolism, NOACs have a safer profile than warfarin and similar efficacy

  • In patients with acute coronary syndrome, NOACs are associated with an incremental risk of bleeding when added to dual antiplatelet therapy, without a reduction in thrombotic risk

Abstract

Vitamin K antagonists (VKAs) have long been the standard of care for treatment of venous thromboembolism (VTE), and thromboprophylaxis in atrial fibrillation (AF). Despite their efficacy, their use requires frequent monitoring and is complicated by drug–drug interactions and the need to maintain a narrow therapeutic window. Since 2009, novel oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, have become alternative options to VKAs owing to their predictable and safe pharmacological profiles. The overall clinical effect of these drugs, which is a balance between ischaemic benefit and bleeding harm, varies according to the clinical scenario. As adjunctive therapy to dual antiplatelet therapy in patients with acute coronary syndrome, NOACs are associated with incremental bleeding risks and modest benefits. For treatment of VTE, NOACs have a safer profile than VKAs and a similar efficacy. In thromboprophylaxis in AF, NOACs are associated with the greatest benefits by reducing both ischaemic events and haemorrhagic complications and might reduce mortality compared with VKAs. The role of NOACs continues to evolve as these drugs are evaluated in different patient populations, including those with renal impairment or with AF and undergoing percutaneous coronary intervention.

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Figure 1: Effect of clinical adverse events (ischaemic stroke, and intracranial and extracranial bleeding) on 30-day mortality.70,71
Figure 2: Net clinical benefit of apixaban, dabigatran, rivaroxaban, and warfarin in prevention of ischaemic stroke and intracranial haemorrhage stratified by risk of ischaemic stroke (CHADS2 score) and bleeding (HAS-BLED score).74
Figure 3: NNT and NNH calculated for the novel oral anticoagulants.
Figure 4: Safety and efficacy of novel oral anticoagulants in the treatment of acute coronary syndrome, venous thromboembolism, and atrial fibrillation.

Change history

  • 02 December 2014

    In the version of this article initially published online and in print, the text "NNH (intracranial haemorrhage)" in the key of Figure 3 should have read "NNT (intracranial haemorrhage)". The error has been corrected for the HTML and PDF versions of the article.

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All the authors researched data for the article, discussed its content, and wrote, reviewed, and edited the manuscript before submission.

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R.M. declares that she is or has been a consultant for Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, CSL Behring, Janssen Pharmaceuticals, Maya Medical, Merck, Regado Biosciences, and Sanofi-Aventis; a member of the Advisory Board for Covidien, Janssen Pharmaceuticals, and Sanofi-Aventis; and has received institutional research grant support from Bristol-Myers Squibb, CardioKinetix, Daiichi Sankyo, Lilly, and Sanofi-Aventis, and The Medicines Company. The other authors declare no competing interests.

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Baber, U., Mastoris, I. & Mehran, R. Balancing ischaemia and bleeding risks with novel oral anticoagulants. Nat Rev Cardiol 11, 693–703 (2014). https://doi.org/10.1038/nrcardio.2014.170

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