title: Rivaroxaban in patients with a recent acute coronary syndrome.
abstract: BACKGROUND
  Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis. Since factor Xa plays a central role in thrombosis, the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome.
  
  
  METHODS
  In this double-blind, placebo-controlled trial, we randomly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months. The primary efficacy end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke.
  
  
  RESULTS
  Rivaroxaban significantly reduced the primary efficacy end point, as compared with placebo, with respective rates of 8.9% and 10.7% (hazard ratio in the rivaroxaban group, 0.84; 95% confidence interval [CI], 0.74 to 0.96; P=0.008), with significant improvement for both the twice-daily 2.5-mg dose (9.1% vs. 10.7%, P=0.02) and the twice-daily 5-mg dose (8.8% vs. 10.7%, P=0.03). The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes (2.7% vs. 4.1%, P=0.002) and from any cause (2.9% vs. 4.5%, P=0.002), a survival benefit that was not seen with the twice-daily 5-mg dose. As compared with placebo, rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) and intracranial hemorrhage (0.6% vs. 0.2%, P=0.009), without a significant increase in fatal bleeding (0.3% vs. 0.2%, P=0.66) or other adverse events. The twice-daily 2.5-mg dose resulted in fewer fatal bleeding events than the twice-daily 5-mg dose (0.1% vs. 0.4%, P=0.04).
  
  
  CONCLUSIONS
  In patients with a recent acute coronary syndrome, rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding. (Funded by Johnson & Johnson and Bayer Healthcare; ATLAS ACS 2-TIMI 51 ClinicalTrials.gov number, NCT00809965.).
authors.affiliation: Thrombolysis in Myocardial Infarction Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. jmega@partners.org
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Mega
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wiviott
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bassand
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Paul
authors.initials: P
authors.lastname: Burton
authors.forename: Marc
authors.initials: M
authors.lastname: Cohen
authors.forename: Nancy
authors.initials: N
authors.lastname: Cook-Bruns
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.forename: Alexei N
authors.initials: AN
authors.lastname: Plotnikov
authors.forename: David
authors.initials: D
authors.lastname: Schneider
authors.forename: Xiang
authors.initials: X
authors.lastname: Sun
authors.forename: Freek W A
authors.initials: FW
authors.lastname: Verheugt
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D015994:Incidence; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069552:Rivaroxaban; D055502:Secondary Prevention; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban