Clinical research study
Death and Disability from Warfarin-Associated Intracranial and Extracranial Hemorrhages

https://doi.org/10.1016/j.amjmed.2006.07.034Get rights and content

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.

Section snippets

Cohort Assembly and Ascertainment of Patient Characteristics

The AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) Study is a cohort of 13,559 adults with diagnosed nonvalvular atrial fibrillation who received care within Kaiser Permanente of Northern California, a large integrated health care delivery system. Details of the cohort assembly have been described.9 Cohort members were identified by searching automated inpatient, outpatient, and electrocardiographic databases for physician-assigned International Classification of Diseases,

Results

During the study period, we identified 72 patients hospitalized with a validated warfarin-associated intracranial hemorrhage during 15,370 person-years of follow-up on warfarin therapy (unadjusted annualized rate 0.47%, 95% confidence interval [CI], 0.37%-0.59%). Of these, 51 (71%) were intracerebral, 15 (21%) were subdural, and 6 were other or unknown types of intracranial hemorrhages. We also identified 98 patients with a validated warfarin-associated major extracranial hemorrhage during

Discussion

Intracranial hemorrhages accounted for approximately 90% of the deaths caused by warfarin-associated hemorrhage, and most of the functional disability among survivors in this cohort of patients taking warfarin for atrial fibrillation. Although the overall rate of hemorrhagic events in the cohort was relatively low, of those patients who sustained a complication from warfarin, intracranial hemorrhage was the primary determinant of death and disability.

The approximately 50% mortality rate from

Conclusion

Intracranial hemorrhages are the primary determinant of poor outcomes from warfarin-associated hemorrhage, resulting in substantially higher rates of death and disability than major extracranial hemorrhages. As a consequence, rather than basing the anticoagulation decision on a patient’s risk for hemorrhage of all types, clinicians should depend primarily on a comparison of the patient’s ischemic stroke risk without warfarin therapy with the risk of intracranial hemorrhage with warfarin

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    This work was supported by Public Health Services research grant AG15478 from the National Institute on Aging, the Eliot B. and Edith C. Shoolman Fund of Massachusetts General Hospital, and a Hartford Geriatrics Health Outcomes Research Scholars Award from the AGS Foundation for Health in Aging.

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