Blood Pressure Control and Risk of Stroke or Systemic Embolism in Patients With Atrial Fibrillation: Results From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial

J Am Heart Assoc. 2015 Dec 1;4(12):e002015. doi: 10.1161/JAHA.115.002015.


Background: Patients with atrial fibrillation (AF) and hypertension are at high risk for stroke. Previous studies have shown elevated risk of stroke in patients with AF who have a history of hypertension (regardless of blood pressure [BP] control) and in patients with elevated BP. We assessed the association of hypertension and BP control on clinical outcomes.

Methods and results: In ARISTOTLE (n=18 201), BP was evaluated as history of hypertension requiring treatment and elevated BP (systolic ≥140 and/or diastolic ≥90 mm Hg) at study entry and any point during the trial. Hazard ratios (HRs) were derived from Cox proportional hazards models including BP as a time-dependent covariate. A total of 15 916 (87.5%) patients had a history of hypertension requiring treatment. In patients with elevated BP measurement at any point during the trial, the rate of stroke or systemic embolism was significantly higher (HR, 1.53; 95% confidence interval [CI], 1.25-1.86), as was hemorrhagic stroke (HR 1.85; 95% CI, 1.26-2.72) and ischemic stroke (HR, 1.50; 95% CI, 1.18-1.90). Rates of major bleeding were lower in patients with a history of hypertension (HR, 0.80; 95% CI, 0.66-0.98) and nonsignificantly lower in patients with elevated BP at study entry (HR, 0.89; 95% CI, 0.77-1.03). The benefit of apixaban versus warfarin on preventing stroke or systemic embolism was consistent among patients with and without a history of hypertension (P interaction=0.27), BP control at baseline (P interaction=0.43), and BP control during the trial (P interaction=0.97).

Conclusions: High BP measurement at any point during the trial was independently associated with a substantially higher risk of stroke or systemic embolism. These results strongly support efforts to treat elevated BP as an important strategy to optimally lower risk of stroke in patients with AF.

Clinical trial registration: URL: Unique identifier: NCT00412984.

Keywords: apixaban; atrial fibrillation; blood pressure control; stroke; systemic embolism.

Publication types

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

MeSH terms

  • Aged
  • Atrial Fibrillation / complications*
  • Brain Ischemia / etiology
  • Brain Ischemia / prevention & control
  • Double-Blind Method
  • Factor Xa Inhibitors / therapeutic use*
  • Female
  • Humans
  • Hypertension / prevention & control*
  • Intracranial Hemorrhages / etiology
  • Intracranial Hemorrhages / prevention & control
  • Male
  • Middle Aged
  • Pyrazoles / therapeutic use*
  • Pyridones / therapeutic use*
  • Risk Factors
  • Stroke / etiology
  • Stroke / prevention & control*
  • Thromboembolism / etiology
  • Thromboembolism / prevention & control*
  • Treatment Outcome


  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban

Associated data