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

Abstract

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: https://ClinicalTrials.gov/. Unique identifier: NCT00412984.

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

© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1

Number of patients according to history of hypertension. DBP indicates diastolic blood pressure; SBP, systolic blood pressure.

Figure 2

Adjusted HRs and 95% CI for the association between elevated blood pressure at any point during the trial and efficacy and safety endpoints. *Elevated blood pressure is defined as the mean of 2 most recent blood pressure measurements having an SBP >140 mm Hg and/or DBP >90 mm Hg. Stroke or systemic embolism outcome was adjusted by age, region, weight, diabetes, moderate valvular disease, previous stroke/TIA/embolism, type of AF, and previous VKA use. Death from any cause, cardiovascular death, and myocardial infarction were adjusted by age, sex, region, weight, moderate valvular disease, left BBB, history of MI, previous stroke/TIA/embolism, anemia, smoking status, previous VKA use, NYHA class, CHADS2 score, and renal function. Major bleeding or clinically relevant nonmajor bleeding and any bleeding were adjusting by age, sex, region, CAD, previous MI, history of bleeding, anemia, CHADS2 score, and renal function. AF indicates atrial fibrillation; BBB, bundle branch block; CAD, coronary artery disease; CI, confidence interval; DBP, diastolic blood pressure; HR, hazard ratio; ISTH, International society on Thrombosis and Hemostasis; MI, myocardial infarction; NYHA, New York Heart Association; SBP, systolic blood pressure; TIA, transient ischemic attack; VKA, vitamin K antagonist.