Risk of major bleeding and stroke associated with the use of vitamin K antagonists, nonvitamin K antagonist oral anticoagulants and aspirin in patients with atrial fibrillation: a cohort study

Br J Clin Pharmacol. 2017 Aug;83(8):1844-1859. doi: 10.1111/bcp.13265. Epub 2017 Mar 24.

Abstract

Aims: Nonvitamin K antagonist oral anticoagulants (NOACs) are now available for the prevention of stroke in patients with atrial fibrillation (AF) as an alternative to vitamin K antagonists (VKA) and aspirin. The comparative effectiveness and safety in daily practice of these different drug classes is still unclear. The objective of this study was to evaluate the risk of major bleeding and stroke in AF patients using NOACs, VKAs or aspirin.

Methods: A retrospective cohort study was conducted among AF patients using the UK Clinical Practice Research Datalink (March 2008-October 2014). New users of VKAs, NOACs and low dose aspirin were followed from the date of first prescription of an antithrombotic drug until the occurrence of stroke or major bleeding. Analyses were adjusted for a history of comorbidities and drug use with Cox regression analysis.

Results: A total of 31 497 patients were eligible for the study. The hazard ratio (HR) of major bleeding was 2.07 [95% confidence interval (CI) 1.27-3.38] for NOACs compared with VKAs, which was mainly attributed by the increased risk of gastrointestinal bleeding (HR 2.63, 95% CI 1.50-4.62). This increased bleeding risk was restricted to women (HR 3.14, 95% CI 1.76-5.60). Aspirin showed a similar bleeding risk as VKAs. NOACs showed equal effectiveness as VKA in preventing ischaemic stroke (HR 1.22, 95% CI 0.67-2.19). VKAs were more effective than aspirin (HR 2.18, 95% CI 1.83-2.59).

Conclusions: NOACs were associated with a higher risk on gastrointestinal bleeding, particularly in women. The use of NOACs in patients who are vulnerable for this type of bleeding should be carefully considered. NOACs and VKAs are equally effective in preventing stroke. Aspirin was not effective in the prevention of stroke in AF.

Keywords: anticoagulants; aspirin; atrial fibrillation; gastrointestinal haemorrhage; intracranial haemorrhage; stroke.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects*
  • Aspirin / adverse effects
  • Atrial Fibrillation / drug therapy*
  • Female
  • Follow-Up Studies
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / epidemiology*
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / adverse effects*
  • Retrospective Studies
  • Risk Factors
  • Stroke / epidemiology*
  • Stroke / prevention & control
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors*
  • Young Adult

Substances

  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Vitamin K
  • Aspirin

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