Edoxaban Versus Warfarin Stratified by Average Blood Pressure in 19 679 Patients With Atrial Fibrillation and a History of Hypertension in the ENGAGE AF-TIMI 48 Trial

Hypertension. 2019 Sep;74(3):597-605. doi: 10.1161/HYPERTENSIONAHA.119.13138. Epub 2019 Jul 29.

Abstract

Hypertension is a risk factor for both stroke and bleeding in patients with atrial fibrillation. Data are sparse regarding the interaction between blood pressure and the efficacy and safety of direct oral anticoagulants. In the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48), 19,679 patients with atrial fibrillation and hypertension were categorized according to average systolic blood pressure (SBP) and diastolic blood pressure (DBP). The primary efficacy and safety end points were the time to the first stroke or systemic embolic event and the time to the first International Society of Thrombosis and Hemostasis major bleeding event, respectively. Risk was calculated using Cox proportional hazards models based on average SBP and DBP and adjusting for 18 clinical characteristics. The efficacy and safety of a higher dose edoxaban regimen (60/30 mg) versus warfarin were evaluated with stratification by average SBP and DBP. Stroke/systemic embolic event occurred significantly more frequently in patients with elevated average SBP (hazard ratio, 2.01; 95% CI, 1.50-2.70 for SBP ≥150 mm Hg relative to 130-139 mm Hg) or DBP (hazard ratio, 2.36; 95% CI, 1.76-3.16 for DBP ≥90 mm Hg relative to 75-<85 mm Hg). The higher dose edoxaban regimen reduced stroke/systemic embolic event across the full range of SBP (Pinteraction=0.55) and DBP (Pinteraction=0.44) compared with warfarin. The higher dose edoxaban regimen reduced the risk of major bleeding events, including intracranial hemorrhage, without modification by average SBP (Pinteraction=0.29). The relative safety of edoxaban was most pronounced in patients with elevated DBP (Pinteraction=0.007). The efficacy and safety of edoxaban were consistent across the full range of SBP, while the superior safety of edoxaban was most pronounced among patients with elevated DBP.

Keywords: atrial fibrillation; humans; hypertension; risk factors; stroke.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / epidemiology*
  • Comorbidity
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / epidemiology*
  • Logistic Models
  • Male
  • Patient Safety
  • Prognosis
  • Proportional Hazards Models
  • Pyridines / therapeutic use*
  • Risk Assessment
  • Severity of Illness Index
  • Stroke / epidemiology
  • Stroke / physiopathology
  • Survival Analysis
  • Thiazoles / therapeutic use*
  • Treatment Outcome
  • Warfarin / therapeutic use*

Substances

  • Pyridines
  • Thiazoles
  • Warfarin
  • edoxaban