Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation and Previous Stroke or Transient Ischemic Attack

Stroke. 2017 Aug;48(8):2142-2149. doi: 10.1161/STROKEAHA.117.017474. Epub 2017 Jun 27.

Abstract

Background and purpose: Limited real-world data exist comparing each non-vitamin K antagonist oral anticoagulant (NOAC) to warfarin in patients with nonvalvular atrial fibrillation who have had a previous ischemic stroke or transient ischemic attack.

Methods: Using MarketScan claims from January 2012 to June 2015, we identified adults newly initiated on oral anticoagulation, with ≥2 diagnosis codes for nonvalvular atrial fibrillation, a history of previous ischemic stroke/transient ischemic attack, and ≥180 days of continuous medical and prescription benefits before anticoagulation initiation. Three analyses were performed comparing 1:1 propensity score-matched cohorts of apixaban versus warfarin (n=2514), dabigatran versus warfarin (n=1962), and rivaroxaban versus warfarin (n=5208). Patients were followed until occurrence of a combined end point of ischemic stroke and intracranial hemorrhage (ICH) or major bleed, switch/discontinuation of index oral anticoagulation, insurance disenrollment, or end of follow-up. Mean follow-up was 0.5 to 0.6 years for all matched cohorts.

Results: Using Cox regression, neither apixaban nor dabigatran reduced the combined primary end point of ischemic stroke or ICH (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.33-1.48 and HR, 0.53; 95% CI, 0.26-1.07) and had nonsignificant effect on hazards of major bleeding (HR, 0.79; 95% CI, 0.38-1.64 and HR, 0.58; 95% CI, 0.26-1.27) versus warfarin. Rivaroxaban reduced the combined end point of ischemic stroke or ICH (HR, 0.45; 95% CI, 0.29-0.72) without an effect on major bleeding (HR, 1.07; 95% CI, 0.71-1.61). ICH occurred at rates of 0.16 to 0.61 events per 100 person-years in the 3 NOAC analyses, with no significant difference for any NOAC versus warfarin.

Conclusions: Results from our study of the 3 NOACs versus warfarin in nonvalvular atrial fibrillation patients with a previous history of stroke/transient ischemic attack are relatively consistent with their respective phase III trials and previous stroke/transient ischemic attack subgroup analyses. All NOACs seemed no worse than warfarin in respect to ischemic stroke, ICH, or major bleeding risk.

Keywords: anticoagulants; atrial fibrillation; dabigatran; rivaroxaban; stroke.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Antithrombins / administration & dosage
  • Antithrombins / adverse effects
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / epidemiology
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / diagnosis
  • Cerebral Hemorrhage / epidemiology
  • Cohort Studies
  • Dabigatran / administration & dosage*
  • Dabigatran / adverse effects
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Ischemic Attack, Transient / diagnosis
  • Ischemic Attack, Transient / drug therapy*
  • Ischemic Attack, Transient / epidemiology
  • Male
  • Middle Aged
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects
  • Pyridones / administration & dosage*
  • Pyridones / adverse effects
  • Retrospective Studies
  • Rivaroxaban / administration & dosage*
  • Rivaroxaban / adverse effects
  • Stroke / diagnosis
  • Stroke / drug therapy*
  • Stroke / epidemiology
  • Treatment Outcome
  • Warfarin / administration & dosage*
  • Warfarin / adverse effects
  • Young Adult

Substances

  • Anticoagulants
  • Antithrombins
  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban
  • Warfarin
  • Rivaroxaban
  • Dabigatran