Apixaban following acute coronary syndromes in patients with prior stroke: Insights from the APPRAISE-2 trial

Am Heart J. 2018 Mar;197:1-8. doi: 10.1016/j.ahj.2017.09.020. Epub 2017 Oct 24.


Background and purpose: Patients with prior stroke are at greater risk for recurrent cardiovascular events post-acute coronary syndromes (ACS) and may have a different risk/benefit profile with antithrombotic therapy than patients without prior stroke.

Methods: We studied 7391 patients with ACS from APPRAISE-2, stratified by the presence or absence of prior stroke. Baseline characteristics and outcomes of cardiovascular death, myocardial infarction (MI), or stroke were compared between groups. Interactions between prior stroke, treatment assignment (apixaban vs placebo), and outcomes were tested before and after multivariable adjustment with Cox proportional hazards models.

Results: A total of 902 patients (12%) had prior stroke. Those with prior stroke were older (69 vs 67 years), had more hypertension (91% vs 77%), peripheral vascular disease (22% vs18%), and impaired renal function (38% vs 30%) but less diabetes (44% vs 48%) than those without prior stroke. Patients with prior stroke vs no prior stroke had higher unadjusted rates of cardiovascular death (4.8% vs 4.0%), MI (11.2% vs 7.1%), and ischemic stroke (3.2% vs 0.9%). Patients with prior stroke assigned to apixaban had similar rates of the composite of cardiovascular death, MI, or stroke compared with those assigned to placebo (HR 1.39; 95% CI 0.92-2.08). Patients without prior stroke assigned to apixaban had similar rates of cardiovascular death, MI, or ischemic stroke compared with those assigned to placebo (HR 0.87; 95% CI 0.73-1.04; P-interaction=.041). Median follow-up was 240 days.

Conclusions: Patients with prior stroke are at higher risk for recurrent cardiovascular events post-ACS and had a differential risk/benefit profile with oral anticoagulation.

Trial registration: ClinicalTrials.gov NCT00831441.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / mortality
  • Acute Coronary Syndrome / prevention & control
  • Aged
  • Blood Coagulation / drug effects*
  • Cause of Death
  • Diabetes Mellitus / epidemiology
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / adverse effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction* / diagnosis
  • Myocardial Infarction* / mortality
  • Myocardial Infarction* / prevention & control
  • Outcome Assessment, Health Care
  • Pyrazoles* / administration & dosage
  • Pyrazoles* / adverse effects
  • Pyridones* / administration & dosage
  • Pyridones* / adverse effects
  • Risk Assessment
  • Risk Factors
  • Secondary Prevention / methods
  • Secondary Prevention / statistics & numerical data
  • Stroke* / blood
  • Stroke* / diagnosis
  • Stroke* / therapy


  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban

Associated data

  • ClinicalTrials.gov/NCT00831441