title: Modification of outcomes with aspirin or apixaban in relation to female and male sex in patients with atrial fibrillation: a secondary analysis of the AVERROES study.
abstract: OBJECTIVE
  The main objective of the present analysis was to assess the effect of treatment with aspirin compared with apixaban on ischemic stroke and major bleeding in women compared with men. Female patients with atrial fibrillation are at increased stroke risk compared with male patients, and the underlying reasons for higher risk are uncertain.
  
  
  METHODS
  Ancillary analysis of the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial, comparing aspirin and apixaban, focused on sex differences. Mean follow-up was 1.1 years.
  
  
  RESULTS
  Women compared with men tended to be older (aspirin, 71.8 versus 68.8 years; apixaban, 71.4 versus 68.6 years), with a higher proportion of those aged≥75 years. Also, women had less peripheral artery disease (aspirin, 2.4% versus 3.7%; apixaban, 1.4% versus 3.0%), more heart failure, and higher mean CHADS2 (congestive heart failure, hypertension, age of 75 years or older, diabetes [1 point each], stroke or transient ischemic attack [2 points]) scores (aspirin, 2.2 versus 2.0; apixaban, 2.1 versus 2.0). Women compared with men had higher ischemic stroke rates (aspirin, 3.99% versus 2.28%; apixaban, 1.55% versus 0.82%) but similar bleeding rates (aspirin, 1.29% versus 1.22%; apixaban, 1.15% versus 1.36%). The relative effect of apixaban compared with aspirin was similar in men and women for both ischemic stroke (women, 3.99% versus 1.55%; hazard ratio, 0.39; 95% confidence interval, 0.23-0.64; men, 2.28% versus 0.82%; hazard ratio, 0.36; 95% confidence interval, 0.19-0.63; Pint=0.84) and major bleeding (women, 1.29% versus 1.15%; hazard ratio, 1.15; 95% confidence interval, 0.59-2.23; men, 1.36% versus 1.22%; hazard ratio, 1.13; 95% confidence interval, 0.64-2.02; Pint=0.96).
  
  
  CONCLUSIONS
  Female patients with atrial fibrillation had higher ischemic stroke rates compared with male patients, but the relative effects of apixaban compared with aspirin on both ischemic stroke and bleeding were similar in men and women.
authors.affiliation: From the University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); and Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (J.E., S.Y., O.S., R.G.H., S.C.). g.y.h.lip@bham.ac.uk.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: From the University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); and Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (J.E., S.Y., O.S., R.G.H., S.C.).
authors.forename: John
authors.initials: J
authors.lastname: Eikelboom
authors.affiliation: From the University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); and Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (J.E., S.Y., O.S., R.G.H., S.C.).
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.affiliation: From the University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); and Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (J.E., S.Y., O.S., R.G.H., S.C.).
authors.forename: Olga
authors.initials: O
authors.lastname: Shestakovska
authors.affiliation: From the University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); and Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (J.E., S.Y., O.S., R.G.H., S.C.).
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hart
authors.affiliation: From the University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); and Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (J.E., S.Y., O.S., R.G.H., S.C.).
authors.forename: Stuart
authors.initials: S
authors.lastname: Connolly
mesh_terms: D000367:Age Factors; D000368:Aged; D001241:Aspirin / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D002545:Brain Ischemia / Q000139:chemically induced* / Q000517:prevention & control; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D015897:Comorbidity; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011720:Pyrazoles / Q000009:adverse effects*; D011728:Pyridones / Q000009:adverse effects*; D012737:Sex Factors; D020521:Stroke / Q000139:chemically induced* / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D001241:Aspirin
keywords: aspirin; atrial fibrillation; hemorrhage; stroke