Death and disability from warfarin-associated intracranial and extracranial hemorrhages

Abstract

Objectives: Little is known about the outcomes of patients who have hemorrhagic complications while receiving warfarin therapy. We examined the rates of death and disability resulting from warfarin-associated intracranial and extracranial hemorrhages in a large cohort of patients with atrial fibrillation.

Methods: We assembled a cohort of 13,559 adults with nonvalvular atrial fibrillation and identified patients hospitalized for warfarin-associated intracranial and major extracranial hemorrhage. Data on functional disability at discharge and 30-day mortality were obtained from a review of medical charts and state death certificates. The relative odds of 30-day mortality by hemorrhage type were calculated using multivariable logistic regression.

Results: We identified 72 intracranial and 98 major extracranial hemorrhages occurring in more than 15,300 person-years of warfarin exposure. At hospital discharge, 76% of patients with intracranial hemorrhage had severe disability or died, compared with only 3% of those with major extracranial hemorrhage. Of the 40 deaths from warfarin-associated hemorrhage that occurred within 30 days, 35 (88%) were from intracranial hemorrhage. Compared with extracranial hemorrhages, intracranial events were strongly associated with 30-day mortality (odds ratio 20.8 [95% confidence interval, 6.0-72]) even after adjusting for age, sex, anticoagulation intensity on admission, and other coexisting illnesses.

Conclusions: Among anticoagulated patients with atrial fibrillation, intracranial hemorrhages caused approximately 90% of the deaths from warfarin-associated hemorrhage and the majority of disability among survivors. When considering anticoagulation, patients and clinicians need to weigh the risk of intracranial hemorrhage far more than the risk of all major hemorrhages.

Figure 1

Risk of death 30 days after hospitalization for warfarin-associated intracranial hemorrhage versus major extracranial hemorrhage; 95% confidence intervals (CIs) (vertical bars). P value refers to the chi-square comparison of mortality rate of intracranial versus extracranial hemorrhage.

Figure 2

Functional deficit at the time of discharge resulting from warfarin-associated intracranial hemorrhage versus major extracranial hemorrhage in hospitalized patients with atrial fibrillation. P value refers to chi-square comparison of discharge deficit between intracranial and extracranial hemorrhage events. Analysis excludes 13 patients whose discharge deficit was not known.