Clinical Research
Heart Rhythm Disorders
A New Risk Scheme to Predict Warfarin-Associated Hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study

https://doi.org/10.1016/j.jacc.2011.03.031Get rights and content
Under an Elsevier user license
open archive

Objectives

The purpose of this study was to develop a risk stratification score to predict warfarin-associated hemorrhage.

Background

Optimal decision making regarding warfarin use for atrial fibrillation requires estimation of hemorrhage risk.

Methods

We followed up 9,186 patients with atrial fibrillation contributing 32,888 person-years of follow-up on warfarin, obtaining data from clinical databases and validating hemorrhage events using medical record review. We used Cox regression models to develop a hemorrhage risk stratification score, selecting candidate variables using bootstrapping approaches. The final model was internally validated by split-sample testing and compared with 6 published hemorrhage risk schemes.

Results

We observed 461 first major hemorrhages during follow-up (1.4% annually). Five independent variables were included in the final model and weighted by regression coefficients: anemia (3 points), severe renal disease (e.g., glomerular filtration rate <30 ml/min or dialysis-dependent, 3 points), age ≥75 years (2 points), prior bleeding (1 point), and hypertension (1 point). Major hemorrhage rates ranged from 0.4% (0 points) to 17.3% per year (10 points). Collapsed into a 3-category risk score, major hemorrhage rates were 0.8% for low risk (0 to 3 points), 2.6% for intermediate risk (4 points), and 5.8% for high risk (5 to 10 points). The c-index for the continuous risk score was 0.74 and 0.69 for the 3-category score, higher than in the other risk schemes. There was net reclassification improvement versus all 6 comparators (from 27% to 56%).

Conclusions

A simple 5-variable risk score was effective in quantifying the risk of warfarin-associated hemorrhage in a large community-based cohort of patients with atrial fibrillation.

Key Words

anticoagulants
atrial fibrillation
hemorrhage
risk prediction
warfarin

Abbreviations and Acronyms

HEMORR2HAGES
hepatic/renal disease, ethanol abuse, malignancy, older age, reduced platelet count, rebleeding risk, hypertension, anemia, genetic factors, excessive fall risk, and stroke
ICD-9
International Classification of Diseases-Ninth Revision, Clinical Modification

Cited by (0)

This study was supported by the National Institute on Aging (R01 AG15478 and K23 AG028978), the National Heart, Lung, and Blood Institute (U19 HL91179 and RC2HL101589), the Eliot B. and Edith C. Shoolman Fund of the Massachusetts General Hospital (Boston, Massachusetts), and a research grant from Daiichi Sankyo, Inc. The funding sources had no role in study design, data collection, data analysis, data interpretation, or preparation of this paper. Dr. Go has received research support from Johnson & Johnson, Inc. Dr. Singer has consulted for Boehringer Ingelheim, Daiichi Sankyo, Inc., Johnson & Johnson, Inc., Merck and Co., Bayer Schering Pharma, and Sanofi-Aventis, Inc., and has received research support from Daiichi Sankyo, Inc. All other authors have reported that they have no relationships to disclose.