Target international normalized ratio values for preventing thromboembolic and hemorrhagic events in Japanese patients with non-valvular atrial fibrillation: results of the J-RHYTHM Registry

Circ J. 2013;77(9):2264-70. doi: 10.1253/circj.cj-13-0290. Epub 2013 May 25.

Abstract

Background: Target anticoagulation levels for warfarin in Japanese patients with non-valvular atrial fibrillation (NVAF) are unclear.

Methods and results: Of 7,527 patients with NVAF, 1,002 did not receive warfarin (non-warfarin group), and the remaining patients receiving warfarin were divided into 5 groups based on their baseline international normalized ratio (INR) of prothrombin time (≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0). Patients were followed-up prospectively for 2 years. Primary endpoints were thromboembolic events (cerebral infarction, transient ischemic attack, and systemic embolism), and major hemorrhage requiring hospital admission. During the follow-up period, thromboembolic events occurred in 3.0% of non-warfarin group, but at lower frequencies in the warfarin groups (2.0, 1.3, 1.5, 0.6, and 1.8%/2 years for INR values of ≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0, respectively; P=0.0059). Major hemorrhage occurred more frequently in warfarin groups (1.5, 1.8, 2.4, 3.3, and 4.1% for INR values ≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0, respectively; P=0.0041) than in non-warfarin group (0.8%/2 years). These trends were maintained when the analyses were confined to patients aged ≥70 years.

Conclusions: An INR of 1.6-2.6 is safe and effective at preventing thromboembolic events in patients with NVAF, particularly patients aged ≥70 years. An INR of 2.6-2.99 is also effective, but associated with a slightly increased risk in major hemorrhage. (UMIN Clinical Trials Registry UMIN000001569)

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants* / administration & dosage
  • Anticoagulants* / adverse effects
  • Asian Continental Ancestry Group
  • Atrial Fibrillation* / drug therapy
  • Atrial Fibrillation* / epidemiology
  • Female
  • Follow-Up Studies
  • Hemorrhage* / chemically induced
  • Hemorrhage* / epidemiology
  • Humans
  • International Normalized Ratio*
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Thromboembolism* / epidemiology
  • Thromboembolism* / etiology
  • Thromboembolism* / prevention & control
  • Warfarin* / administration & dosage
  • Warfarin* / adverse effects

Substances

  • Anticoagulants
  • Warfarin