Mortality risk in atrial fibrillation: the role of aspirin, vitamin K and non-vitamin K antagonists

Emilie Gieling, Frank de Vries*, Rachael Williams, Hein A W van Onzenoort, Anthonius de Boer, Vincent Ten Cate, Cornelis Kramers, Andrea Burden

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background As an alternative to vitamin K antagonist and low-dose aspirin (< 325 mg), non-vitamin K oral anticoagulants are available for the prevention of stroke in patients with atrial fibrillation. However, the mortality risk associated with these drugs in daily practice remains unclear. Objective To evaluate the risk of all-cause mortality associated with non-Vitamin K antagonist oral anticoagulants, vitamin K antagonists or aspirin in patients with atrial fibrillation. Setting A cohort study conducted among atrial fibrillation patients using the UK Clinical Practice Research Datalink (March 2008-October 2014). Method New users of vitamin K antagonists, non vitamin K oral anticoagulants, low-dose aspirin, or combination therapy were followed from the date of first prescription to the date of death, as recorded in the UK datalink. Cox proportional hazard models estimated the hazard ratio (HR) of all-cause mortality for users of NOACs, aspirin, or combination use, as compared to vitamin K antagonist. Analyses were adjusted for confounders. Main outcome measure All-cause mortality. Results We identified 31,497 patients. Non vitamin K antocoagulant use (adjusted HR [aHR] = 1.42; 95% Confidence Interval [CI] 1.18-1.71) and aspirin use (aHR = 1.64; 95% CI 1.57-1.77) were both significantly associated with a higher mortality risk than use of vitamin K antagonists. The higher mortality risk for the non vitamin K anticoagulant use was observed in men (aHR = 1.72; 95% CI 1.25-2.36), but not in women (aHR = 1.28; 95% CI 0.92-1.79. Compared to vitamin K antagonists, mortality risk associated with the non vitamin K anticoagulants and aspirin use was significantly increased in patients with higher stroke risk (CHA2DS2-VASc > 2). Conclusion Non vitamin K oral anticoagulants are associated with a higher risk on all-cause mortality, particularly in men and in patients with higher stroke risk.

Original languageEnglish
Pages (from-to)1536-1544
Number of pages9
JournalInternational Journal of Clinical Pharmacy
Issue number6
Early online date8 Oct 2019
Publication statusPublished - Dec 2019


  • Anticoagulants
  • Atrial fibrillation
  • Coumarins
  • Mortality
  • NOACs
  • Non vitamin K oral anticoagulants
  • Vitamin K antagonists

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