title: 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.
  
  
  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.
  
  
  BACKGROUND
  URL: https://ClinicalTrials.gov/. Unique identifier: NCT00412984.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (M.P.R., D.W., L.T., J.H.A., R.D.L., C.B.G.).
authors.forename: Meena P
authors.initials: MP
authors.lastname: Rao
authors.affiliation: Oslo University Hospital, Oslo, Norway (S.H.).
authors.forename: Sigrun
authors.initials: S
authors.lastname: Halvorsen
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (M.P.R., D.W., L.T., J.H.A., R.D.L., C.B.G.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Wojdyla
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (M.P.R., D.W., L.T., J.H.A., R.D.L., C.B.G.).
authors.forename: Laine
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (M.P.R., D.W., L.T., J.H.A., R.D.L., C.B.G.).
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.affiliation: Boston University Medical Center, Boston, MA (E.M.H.).
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ (M.H.).
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.affiliation: INECO Neurociencias Oroño, Rosario, Santa Fe, Argentina (C.B.).
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Bahit
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (M.P.R., D.W., L.T., J.H.A., R.D.L., C.B.G.).
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: G. D'Annunzio Universita-Chieti and Fondazione Toscana G. Monasterio, Pisa, Italy (R.D.C.).
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: Ankara University, Ankara, Turkey (C.E.).
authors.forename: Cetin
authors.initials: C
authors.lastname: Erol
authors.affiliation: Tokai University School of Medicine, Isehara, Japan (S.G.).
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
authors.affiliation: Universidad de La Frontera, Temuco, Chile (F.L.).
authors.forename: Fernando
authors.initials: F
authors.lastname: Lanas
authors.affiliation: Lady Davis Carmel Medical Center and the Ruth and Bruce Rappaport School of Medicine, Technion-IIT, Haifa, Israel (B.S.L.).
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.affiliation: Hospital UnitWest, Herning/Holstbro, Denmark (S.H.).
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN (B.J.G.).
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden (L.W.).
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (M.P.R., D.W., L.T., J.H.A., R.D.L., C.B.G.).
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000150:complications*; D002545:Brain Ischemia / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000517:prevention & control*; D020300:Intracranial Hemorrhages / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban
keywords: apixaban; atrial fibrillation; blood pressure control; stroke; systemic embolism