Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin

doi:10.1016/S0002-9343(98)00198-3

The American Journal of Medicine

Volume 105, Issue 2, August 1998, Pages 91-99

Presented in part at the Annual Meeting of the Society of General Internal Medicine, May 6, 1995, San Diego, California.

https://doi.org/10.1016/S0002-9343(98)00198-3 Get rights and content

Abstract

PURPOSE: To evaluate the accuracy and clinical utility of the Outpatient Bleeding Risk Index for estimating the probability of major bleeding in outpatients treated with warfarin. The index was previously derived in a retrospective cohort of 556 patients from a different hospital (derivation cohort).

SUBJECTS AND METHODS: We enrolled 264 outpatients starting warfarin (validation cohort) to validate the index prospectively. All patients were identified upon hospital discharge, and physician estimates of the probability of major bleeding were obtained before discharge in the validation cohort.

RESULTS: Major bleeding occurred in 87 of 820 outpatients (6.5%/yr). The index included four independent risk factors for major bleeding: age 65 years or greater; history of gastrointestinal bleeding; history of stroke; and one or more of four specific comorbid conditions. In the validation cohort, the index predicted major bleeding: the cumulative incidence at 48 months was 3% in 80 low-risk patients, 12% in 166 intermediate-risk patients, and 53% in 18 high-risk patients (c index, 0.78). The index performed better than physicians, who estimated the probability of major bleeding no better than expected by chance. Of the 18 episodes of major bleeding that occurred in high-risk patients, 17 were potentially preventable.

CONCLUSIONS: The Outpatient Bleeding Risk Index prospectively classified patients according to risk of major bleeding and performed better than physicians. Major bleeding may be preventable in many high-risk patients by avoidance of over-anticoagulation and nonsteroidal anti-inflammatory agents.

Section snippets

Patients

The Outpatient Bleeding Risk Index was derived in a cohort of 565 patients who started outpatient warfarin therapy upon discharge from Brigham and Women’s Hospital (Boston, Massachusetts) between 1977 and 1983. This derivation cohort was assembled in 1983 and followed through 1985 20, 21. Three patients were lost to follow-up at discharge and 6 patients had incomplete follow-up. Thus, follow-up for major bleeding was available for 556 patients (98%).

The Outpatient Bleeding Risk Index was tested

Results

Patients in the derivation and validation cohorts were similar in age, gender, INR at discharge, and length of outpatient warfarin therapy, but they differed in race, indications for therapy, and comorbid conditions (Table 1).

Major bleeding occurred in 65 of the 556 patients (12%) in the derivation cohort; the average rate of major bleeding was 7% per year of therapy. Ten (2%) patients died from intracranial (n = 7), gastrointestinal (n = 1), or intra-abdominal bleeding (n = 1); 1 patient had

Discussion

This study provides evidence of the accuracy and clinical utility of the Outpatient Bleeding Risk Index for stratifying patients by their risk of major bleeding during outpatient therapy with warfarin. First, the Index prospectively classified patients in the independent validation cohort into three groups with different cumulative risks of major bleeding. The Index discriminated between patients who developed major bleeding and those who did not both in the derivation and validation cohorts,

Acknowledgements

We thank Tracey Flowers for her help in preparing this manuscript.

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^☆: Supported in part by grants from the NIH (#AG-09657, K08-A600712), Claude D. Pepper Older Americans Independent Center (#AG-10418), and the American Federation for Aging Research. Dr. Beyth was a Merck/AFAR Fellow in Geriatric Clinical Pharmacology, and a recipient of an NIA Clinical Investigator Award.

^∗: Access the “Journal Club” discussion of this paper at http://www.elsevier.com/locate/ajmselect/

²: Dr. Landefeld was a Senior Research Associate, Health Services Research and Development Service, Department of Veterans Affairs. Dr. Landefeld is now with the University of California, San Francisco-Mount Zion Center on Aging, the Division of Geriatrics, University of California, San Francisco and the San Francisco Veterans Affairs Medical Center.

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Clinical StudiesProspective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin ∗☆,

Abstract

Section snippets

Patients

Results

Discussion

Acknowledgements

J Am Coll Cardiol

Lancet

J Clin Epidemiol

Mayo Clin Proc

Am J Med

Am J Med

Am J Med

J Clin Epidemiol

Lancet

Am J Med

Am J Cardiol

Am J Med

The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation

NEJM

Prevention of venous thromboembolism

Chest

Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation

NEJM

Trial of different intensities of anticoagulant therapy in patients with substitute heart valves

NEJM

The effect of warfarin on mortality and reinfarction after myocardial infarction

NEJM

Stroke prevention in atrial fibrillation study. Final results

Circulation

Failure to prescribe warfarin to patients with nonrheumatic atrial fibrillation

J Gen Intern Med

Why isn’t warfarin prescribed to patients with nonrheumatic atrial fibrillation? A study of physicians’ opinions and their relationship to clinical characteristics and the physicians’ prescribing practices

J Gen Intern Med

Physician variation in anticoagulating patients with atrial fibrillation

Arch Intern Med

Anticoagulation in atrial fibrillation. Does efficacy in clinical trials translate into effectiveness in practice?

Arch Intern Med

Physicians’ attitudes toward oral anticoagulants and antiplatelet agents for stroke prevention in elderly patients with atrial fibrillation

Arch Intern Med

Physician attitudes about anticoagulation for nonvalvular atrial fibrillation

Arch Intern Med

Anticoagulant therapy in cerebral infarctionreport of cooperative study

Neurology

Clinical Studies
Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin ∗☆,