title: History of bleeding and outcomes with apixaban versus warfarin in patients with atrial fibrillation in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.
abstract: OBJECTIVE
  History of bleeding strongly influences decisions for anticoagulation in atrial fibrillation (AF). We analyzed outcomes in relation to history of bleeding and randomization in ARISTOTLE trial patients.
  
  
  RESULTS
  The on-treatment safety population included 18,140 patients receiving at least 1 dose of study drug (apixaban) or warfarin. Centrally adjudicated outcomes in relation to bleeding history were analyzed using a Cox proportional hazards model adjusted for randomized treatment and established risk factors. Efficacy end points were analyzed on the randomized (intention to treat) population. A bleeding history was reported at baseline in 3,033 patients (16.7%), who more often were male, with a history of prior stroke/transient ischemic attack/systemic embolism and diabetes; higher CHADS2 scores, age, and body weight; and lower creatinine clearance and mean systolic blood pressure. Major (but not intracranial) bleeding occurred more frequently in patients with versus without a history of bleeding (adjusted hazard ratio 1.35, 95% CI 1.14-1.61). There were no significant interactions between bleeding history and treatment for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding, with fewer outcomes with apixaban versus warfarin for all of these outcomes independent of the presence/absence of a bleeding history.
  
  
  CONCLUSIONS
  In patients with AF in a randomized clinical trial of oral anticoagulants, a history of bleeding is associated with several risk factors for stroke and portends a higher risk of major-but not intracranial-bleeding, during anticoagulation. However, the beneficial effects of apixaban over warfarin for stroke, hemorrhagic stroke, death, or major bleeding remains consistent regardless of history of bleeding.
authors.affiliation: Institute of Cardiology and Center of Excellence on Aging, G. d'Annunzio University, Chieti, Italy. Electronic address: rdecater@unich.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Andersson
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Sana M
authors.initials: SM
authors.lastname: Al-Khatib
authors.affiliation: INECO Neurociencias Oroño, Rosario, Santa Fe, Argentina.
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Bahit
authors.affiliation: Tokai University School of Medicine, Isehara, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.affiliation: J.W. Goethe-University, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hohnloser
authors.affiliation: Boston University Medical Center, Boston, MA.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.affiliation: Universidad de La Frontera, Temuco, Chile.
authors.forename: Fernando
authors.initials: F
authors.lastname: Lanas
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: Hospital Universitario La Paz, IdiPaz Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: López-Sendón
authors.affiliation: Institute of Cardiology and Center of Excellence on Aging, G. d'Annunzio University, Chieti, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Renda
authors.affiliation: Queen Elizabeth Hospital, Adelaide, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Horowitz
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Durham, NC.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications*; D016903:Drug Monitoring; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010043:Outcome and Process Assessment, Health Care; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin