title: Apixaban with antiplatelet therapy after acute coronary syndrome.
abstract: BACKGROUND
  Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg twice daily, with placebo, in addition to standard antiplatelet therapy, in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events.
  
  
  RESULTS
  The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events. With a median follow-up of 241 days, the primary outcome of cardiovascular death, myocardial infarction, or ischemic stroke occurred in 279 of the 3705 patients (7.5%) assigned to apixaban (13.2 events per 100 patient-years) and in 293 of the 3687 patients (7.9%) assigned to placebo (14.0 events per 100 patient-years) (hazard ratio with apixaban, 0.95; 95% confidence interval [CI], 0.80 to 1.11; P=0.51). The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infarction (TIMI) definition occurred in 46 of the 3673 patients (1.3%) who received at least one dose of apixaban (2.4 events per 100 patient-years) and in 18 of the 3642 patients (0.5%) who received at least one dose of placebo (0.9 events per 100 patient-years) (hazard ratio with apixaban, 2.59; 95% CI, 1.50 to 4.46; P=0.001). A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo.
  
  
  CONCLUSIONS
  The addition of apixaban, at a dose of 5 mg twice daily, to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events. (Funded by Bristol-Myers Squibb and Pfizer; APPRAISE-2 ClinicalTrials.gov number, NCT00831441.).
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27715, USA. john.h.alexander@duke.edu
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.forename: Stefan
authors.initials: S
authors.lastname: James
authors.forename: Rakhi
authors.initials: R
authors.lastname: Kilaru
authors.forename: Yaohua
authors.initials: Y
authors.lastname: He
authors.forename: Puneet
authors.initials: P
authors.lastname: Mohan
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: Shaun
authors.initials: S
authors.lastname: Goodman
authors.forename: Freek W
authors.initials: FW
authors.lastname: Verheugt
authors.forename: Marcus
authors.initials: M
authors.lastname: Flather
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Danny
authors.initials: D
authors.lastname: Liaw
authors.forename: Steen E
authors.initials: SE
authors.lastname: Husted
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Sendon
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.forename: Petr
authors.initials: P
authors.lastname: Jansky
authors.forename: Harald
authors.initials: H
authors.lastname: Darius
authors.forename: Dragos
authors.initials: D
authors.lastname: Vinereanu
authors.forename: Jan H
authors.initials: JH
authors.lastname: Cornel
authors.forename: Frank
authors.initials: F
authors.lastname: Cools
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Leiva-Pons
authors.forename: Matyas
authors.initials: M
authors.lastname: Keltai
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.forename: Prem
authors.initials: P
authors.lastname: Pais
authors.forename: Alexander
authors.initials: A
authors.lastname: Parkhomenko
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyllo
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.forename: Harvey
authors.initials: H
authors.lastname: White
authors.forename: Mikhail
authors.initials: M
authors.lastname: Ruda
authors.forename: Margarida
authors.initials: M
authors.lastname: Geraldes
authors.forename: Jack
authors.initials: J
authors.lastname: Lawrence
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D000789:Angina, Unstable / Q000453:epidemiology / Q000517:prevention & control; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D065427:Factor Xa Inhibitors; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use*; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D065427:Factor Xa Inhibitors; D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D001241:Aspirin