title: Effect of apixaban on brain infarction and microbleeds: AVERROES-MRI assessment study.
abstract: BACKGROUND
  Clinical and subclinical (covert) stroke is a cause of cognitive loss and functional impairment. In the AVERROES trial, we performed serial brain magnetic resonance imaging (MRI) scans in a subgroup to explore the effect of apixaban, compared with aspirin, on clinical and covert brain infarction and on microbleeds in patients with atrial fibrillation.
  
  
  METHODS
  We performed brain MRI (T1, T2, fluid-attenuated inversion recovery, and T2* gradient echo sequences) in 1,180 at baseline and in 931 participants at follow-up. Mean interval from baseline to follow-up MRI scans was 1.0 year. The primary outcome was a composite of clinical ischemic stroke and covert embolic pattern infarction (defined as infarction >1.5 cm, cortical-based infarction, or new multiterritory infarction). Secondary outcomes included new MRI-detected brain infarcts and microbleeds and change in white matter hyperintensities.
  
  
  RESULTS
  Baseline MRI scans revealed brain infarct(s) in 26.2% and microbleed(s) in 10.5%. The rate of the primary outcomes was 2.0% in the apixaban group and 3.3% in the aspirin group (hazard ratio [HR] 0.55; 0.27-1.14) from baseline to follow-up MRI scan (mean duration of follow-up: 1 year). In those who completed baseline and follow-up MRI scans, the rate of new infarction detected on MRI was 2.5% in the apixaban group and 2.2% in the aspirin group (HR 1.09; 0.47-2.52), but new infarcts were smaller in the apixaban group (P = .03). There was no difference in proportion with new microbleeds on follow-up MRI (HR 0.92; 0.53-1.60) between treatment groups.
  
  
  CONCLUSIONS
  Apixaban treatment was associated with a nonsignificant trend toward reduction in the composite of clinical ischemic stroke and covert embolic-pattern infarction and did not increase the number of microbleeds in patients with atrial fibrillation compared with aspirin.
authors: Population Health Research Institute, McMaster University, and Hamilton Health Sciences, Hamilton, ON, Canada; HRB-Clinical Research Facility, NUI Galway, Galway, Ireland. Electronic address: odonnm@mcmaster.ca.
authors: Martin J
authors: MJ
authors: O'Donnell
authors: Population Health Research Institute, McMaster University, and Hamilton Health Sciences, Hamilton, ON, Canada.
authors: John W
authors: JW
authors: Eikelboom
authors: Population Health Research Institute, McMaster University, and Hamilton Health Sciences, Hamilton, ON, Canada.
authors: Salim
authors: S
authors: Yusuf
authors: Department of Neurology, University Hospital, Essen, Germany.
authors: Hans-Christoph
authors: HC
authors: Diener
authors: Population Health Research Institute, McMaster University, and Hamilton Health Sciences, Hamilton, ON, Canada.
authors: Robert G
authors: RG
authors: Hart
authors: Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
authors: Eric E
authors: EE
authors: Smith
authors: Department of Neurology, University of Toronto, Toronto, ON, Canada.
authors: David J
authors: DJ
authors: Gladstone
authors: Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors: Mukul
authors: M
authors: Sharma
authors: Estudios Clinicos Latinoamerica, Rosario, Argentina.
authors: Rafael
authors: R
authors: Dias
authors: University of Missouri, Colombia, MO.
authors: Greg
authors: G
authors: Flaker
authors: Instituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil.
authors: Alvaro
authors: A
authors: Avezum
authors: Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Jun
authors: J
authors: Zhu
authors: Population Health Research Institute, McMaster University, and Hamilton Health Sciences, Hamilton, ON, Canada.
authors: Gayle
authors: G
authors: Lewis
authors: Population Health Research Institute, McMaster University, and Hamilton Health Sciences, Hamilton, ON, Canada.
authors: Stuart
authors: S
authors: Connolly
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D001921:Brain / Q000000981:diagnostic imaging; D020520:Brain Infarction / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000000981:diagnostic imaging; D004617:Embolism / Q000209:etiology / Q000517:prevention & control; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011720:Pyrazoles / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*
chemical_list: D065427:Factor Xa Inhibitors; D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D001241:Aspirin