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Is concomitant aspirin helping novel oral anticoagulants? Focus on apixaban
  1. James J DiNicolantonio1,
  2. Ales Tomek2,
  3. Pascal Meier3,4,
  4. James H O'Keefe1,
  5. Fabrizio D'Ascenzo5,
  6. Enrico Cerrato5,
  7. Saurav Chatterjee6 and
  8. Giuseppe Biondi-Zoccai7
  1. 1Mid America Heart Institute, St. Luke's Hospital, Kansas City, Missouri, USA
  2. 2Department of Neurology, Charles University in Prague, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic
  3. 3The Heart Hospital, University College London Hospitals UCLH, London, UK
  4. 4Yale Medical School, New Haven, Connecticut, USA
  5. 5Division of Cardiology, University of Turin, Città Della Salute e Della Scienza, Torino, Italy
  6. 6St Luke's Roosevelt Hospital Center, New York, New York, USA
  7. 7Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
  1. Correspondence to Dr James J DiNicolantonio; jjdinicol{at}

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Apixaban is the third novel oral anticoagulant approved by the Food and Drug Administration for the reduction in the risk of stroke in patients with atrial fibrillation. Apixaban showed a significant reduction in mortality as well as a reduction in strokes compared with warfarin in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.1 However, it is unclear how much of this ‘benefit’ was derived from the negative benefit to risk ratio (RR) when combining aspirin with warfarin compared with warfarin alone. Approximately one-third of patients received combination warfarin-acetylsalicylic acid (ASA) therapy in ARISTOTLE at baseline (31.3% on apixaban, 30.5% on warfarin), with approximately 20–25% of patients receiving aspirin with long-term anticoagulation,2 despite the fact that only 14% of patients randomised to warfarin had a definitive indication for concomitant aspirin therapy (ie, patients having a previous myocardial infarction (MI)). Most patients receiving aspirin had arterial vascular disease, but the majority did not have a recent MI, which is a more appropriate indication for concomitant warfarin-ASA therapy (ie, a history of MI <6 months, depending on the stent used). The high percentage of warfarin-ASA use in ARISTOTLE, despite no clear indication for many of these individuals, introduces a significant confounder. Did aspirin increase the harm in patients on warfarin over and above what would be seen in patients receiving apixaban?


A total of 20–25% of patients were on combination warfarin-ASA in the ARISTOTLE trial, despite the fact that only 14% and 16% of patients had a history or occurrence of MI before …

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