Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation

Stroke. 2014 May;45(5):1304-12. doi: 10.1161/STROKEAHA.113.004506. Epub 2014 Apr 17.

Abstract

Background and purpose: Intracranial hemorrhage (ICH) is a life-threatening complication of anticoagulation.

Methods: We investigated the rate, outcomes, and predictors of ICH in 14 264 patients with atrial fibrillation from Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Cox proportional hazards modeling was used.

Results: During 1.94 years (median) of follow-up, 172 patients (1.2%) experienced 175 ICH events at a rate of 0.67% per year. The significant, independent predictors of ICH were race (Asian: hazard ratio, 2.02; 95% CI, 1.39-2.94; black: hazard ratio, 3.25; 95% CI, 1.43-7.41), age (1.35; 1.13-1.63 per 10-year increase), reduced serum albumin (1.39; 1.12-1.73 per 0.5 g/dL decrease), reduced platelet count below 210×10(9)/L (1.08; 1.02-1.13 per 10×10(9)/L decrease), previous stroke or transient ischemic attack (1.42; 1.02-1.96), and increased diastolic blood pressure (1.17; 1.01-1.36 per 10 mm Hg increase). Predictors of a reduced risk of ICH were randomization to rivaroxaban (0.60; 0.44-0.82) and history of congestive heart failure (0.65; 0.47-0.89). The ability of the model to discriminate individuals with and without ICH was good (C-index, 0.69; 95% CI, 0.64-0.73).

Conclusions: Among patients with atrial fibrillation treated with anticoagulation, the risk of ICH was higher among Asians, blacks, the elderly, and in those with previous stroke or transient ischemic attack, increased diastolic blood pressure, and reduced platelet count or serum albumin at baseline. The risk of ICH was significantly lower in patients with heart failure and in those who were randomized to rivaroxaban instead of warfarin. The external validity of these findings requires testing in other atrial fibrillation populations.

Keywords: anticoagulation; atrial fibrillation; intracranial hemorrhage; risk prediction.

Publication types

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

MeSH terms

  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Asian People / ethnology
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / epidemiology
  • Black People / ethnology
  • Double-Blind Method
  • Embolism / prevention & control
  • Factor Xa Inhibitors
  • Female
  • Humans
  • Intracranial Hemorrhages / blood
  • Intracranial Hemorrhages / chemically induced
  • Intracranial Hemorrhages / epidemiology*
  • Intracranial Hemorrhages / physiopathology
  • Male
  • Morpholines / administration & dosage
  • Morpholines / adverse effects*
  • Prospective Studies
  • Rivaroxaban
  • Stroke / prevention & control
  • Thiophenes / administration & dosage
  • Thiophenes / adverse effects*
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors
  • Warfarin / administration & dosage
  • Warfarin / adverse effects*

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Morpholines
  • Thiophenes
  • Vitamin K
  • Warfarin
  • Rivaroxaban