title: Efficacy and safety of apixaban compared with aspirin in patients who previously tried but failed treatment with vitamin K antagonists: results from the AVERROES trial.
abstract: OBJECTIVE
  The AVERROES double-blinded, randomized trial demonstrated that apixaban reduces the risk of stroke or systemic embolism (SSE) by 55% compared with aspirin without an increase in major bleeding in patients with atrial fibrillation either who previously tried but failed vitamin K antagonists (VKA) therapy or who were expected to be unsuitable for VKA therapy. In this pre-specified analysis, we explored the consistency of the results in the subgroup of patients who tried but failed VKA therapy.
  
  
  RESULTS
  Of 5599 patients, 2216 (40%) had previously failed VKA treatment [main reasons: poor international normalized ratio (INR) control 42%, refusal 37%, bleeding on VKA 8%]. Compared with those expected to be unsuitable for VKA therapy, those who had previously failed were older, more often male, had higher body mass index, more likely to have moderate renal impairment and a history of stroke and less likely to have heart failure or to be medically undertreated. The effects of apixaban compared with aspirin were consistent in those who previously failed and those who were expected to be unsuitable, for both SSE (P interaction 0.13) and major bleeding (P interaction 0.74) and were also consistent among different subgroups of patients who had previously failed VKA therapy defined by reasons for unsuitability, age, sex, renal function, CHADS2 score, aspirin dose, duration, indication, and quality of INR control of prior VKA use.
  
  
  CONCLUSIONS
  The efficacy and safety of apixaban compared with aspirin is consistent in subgroups of patients who have previously attempted but failed VKA therapy, irrespective of the reason for discontinuation.
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, ON, Canada Academic Medical Center, Amsterdam, The Netherlands michiel.coppens@phri.ca.
authors.forename: Michiel
authors.initials: M
authors.lastname: Coppens
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: David
authors.initials: D
authors.lastname: Synhorst
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Shestakovska
authors.affiliation: Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Connolly
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control*; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D011720:Pyrazoles; D011728:Pyridones; D014812:Vitamin K; C522181:apixaban; D001241:Aspirin
keywords: Apixaban; Aspirin; Atrial fibrillation; Bleeding; Stroke; Vitamin K antagonists