Development of a Contemporary Bleeding Risk Model for Elderly Warfarin Recipients

      Background and purpose

      Develop and validate a contemporary bleeding risk model to guide the clinical use of warfarin in the elderly atrial fibrillation (AF) population.


      Chart-abstracted data from the National Registry of Atrial Fibrillation was combined with Medicare part A claims to identify major bleeding events requiring hospitalization. Using a split-sample technique, candidate variables that provided statistically stable relationships with major bleeding events were selected for model development. Three risk categories were created and validated. The new model was compared to existing bleeding risk models using c-statistics and Kaplan-Meier curves.


      Model development and validation was conducted on 26,345 AF patients who were > 65 years of age and had been discharged from the hospital while receiving warfarin therapy. The following eight variables were included in the final risk score model: age ≥ 70 years; gender; remote bleeding; recent (ie, during index hospitalization) bleeding; alcohol/drug abuse; diabetes; anemia; and antiplatelet use. Bleeding rates were 0.9%, 2.0%, and 5.4%, respectively, for the groups with low, moderate, and high risk, compared to the bleeding rates for groups with moderate risk (1.5% and 1.0%) and high risk (1.8% and 2.5%) from other models.


      Using a nationally derived data set, we developed a model based on contemporary practice standards for determining major bleeding risk among AF patients receiving warfarin therapy. The larger sample size afforded the opportunity to incorporate additional risk factors. In addition, since the majority of our population was > 65 years of age, we had greater ability to stratify risk among the elderly.



      AF (atrial fibrillation), HR (hazard ratio), INR (international normalized ratio), MI (myocardial infarction), NSAID (nonsteroidal antiinflammatory drug), OBRI (Outpatient Bleeding Risk Index), ROC (receiver operating characteristic)
      To read this article in full you will need to make a payment
      Subscribe to CHEST
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials.
        Arch Intern Med. 1994; 154 (Atrial Fibrillation Investigators): 1449-1457
        • Stafford RS
        • Singer DE
        Recent national patterns of warfarin use in atrial fibrillation.
        Circulation. 1998; 97: 1231-1233
        • Gage BF
        • Boechler M
        • Doggette AL
        • et al.
        Adverse outcomes and predictors of underuse of antithrombotic therapy in Medicare beneficiaries with chronic atrial fibrillation.
        Stroke. 2000; 31: 822-827
        • Jencks SF
        • Cuerdon T
        • Burwen DR
        • et al.
        Quality of medical care delivered to Medicare beneficiaries: a profile at state and national levels.
        JAMA. 2000; 284: 1670-1676
        • Jencks SF
        • Huff ED
        • Cuerdon T
        Change in the quality of care delivered to Medicare beneficiaries, 1998–1999 to 2000–2001.
        JAMA. 2003; 289: 305-312
        • McCrory DC
        • Matchar DB
        • Samsa G
        • et al.
        Physician attitudes about anticoagulation for nonvalvular atrial fibrillation in the elderly.
        Arch Intern Med. 1995; 155: 277-281
        • Landefeld CS
        • Goldman L
        Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy.
        Am J Med. 1989; 87: 144-152
        • Beyth RJ
        • Quinn LM
        • Landefeld CS
        Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin.
        Am J Med. 1998; 105: 91-99
        • Wells PS
        • Forgie MA
        • Simms M
        • et al.
        The Outpatient Bleeding Risk Index: validation of a tool for predicting bleeding rates in patients treated for deep venous thrombosis and pulmonary embolism.
        Arch Intern Med. 2003; 163: 917-920
        • Aspinall SL
        • De Sanzo BE
        • Trilli LE
        • et al.
        Bleeding risk index in an anticoagulation clinic: assessment by indication and implications for care.
        J Gen Intern Med. 2005; 20: 1008-1013
        • Kuijer PMM
        • Hutten BA
        • Prins MH
        • et al.
        Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism.
        Arch Intern Med. 1999; 159: 457-460
        • Howard PA
        • Ellerbeck EF
        • Engelman KK
        • et al.
        Warfarin for stroke prevention in octogenarians with atrial fibrillation.
        Am J Geriatr Cardiol. 2001; 10: 139-144
        • van der Meer FJM
        • Rosendaal FR
        • Vandenbroucke JP
        • et al.
        Bleeding complications in oral anticoagulant therapy: an analysis of risk factors.
        Arch Intern Med. 1993; 153: 1557-1562
        • Hylek EM
        • Singer DE
        Risk factors for intracranial hemorrhage in outpatients taking warfarin.
        Ann Intern Med. 1994; 120: 897-902
        • Fihn SD
        • McDonell M
        • Martin D
        • et al.
        Risk factors for complications of chronic anticoagulation.
        Ann Intern Med. 1993; 118: 511-520
      2. The Stroke Prevention in Atrial Fibrillation Investigators. Bleeding during antithrombotic therapy in patients with atrial fibrillation.
        Arch Intern Med. 1996; 156: 409-416
        • Fihn SD
        • Callahan CM
        • Martin DC
        • et al.
        The risk for and severity of bleeding complications in elderly patients treated with warfarin.
        Ann Intern Med. 1996; 124: 970-979
        • Wehinger C
        • Stollberger C
        • Langer T
        • et al.
        Evaluation of risk factors for stroke/embolism and of complications due to anticoagulant therapy in atrial fibrillation.
        Stroke. 2001; 32: 2246-2252
        • Pengo V
        • Legnani C
        • Noventa F
        • et al.
        Oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and risk of bleeding: a multicenter inception cohort study.
        Thromb Haemost. 2001; 85: 418-422
        • Howard PA
        • Dunn MI
        Update on drug interactions: warfarin and anti-infective agents.
        J Respir Dis. 1998; 19: 1037-1046
        • Freedman MD
        • Olatidoye AG
        Clinically significant drug interactions with the oral anticoagulants.
        Drug Saf. 1994; 10: 381-394
        • Howard PA
        • Ellerbeck EF
        • Engelman KK
        • et al.
        The nature and frequency of potential warfarin drug interactions that increase the risk of bleeding in patients with atrial fibrillation.
        Pharmacoepidemiol Drug Saf. 2002; 11: 569-576
        • Quilliam BJ
        • Lapane KL
        • Eaton CB
        • et al.
        Effects of antiplatelet and anticoagulant agents on risk of hospitalization for bleeding among a population of elderly nursing home stroke survivors.
        Stroke. 2001; 32: 2299-2304
        • Shireman TI
        • Howard PA
        • Kresowik TF
        • et al.
        Combined anticoagulant-antiplatelet use and major bleeding events in elderly atrial fibrillation patients.
        Stroke. 2004; 35: 2362-2367
        • Fisher ES
        • Wennberg JE
        • Stukel TA
        • et al.
        Hospital readmission rates for cohorts of Medicare beneficiaries in Boston and New Haven.
        N Engl J Med. 1994; 331: 989-995
        • Tirschwell DL
        • Longstreth WT
        Validating administrative data in stroke research.
        Stroke. 2002; 33: 2465-2470
        • Hosmer DW
        • Lemeshow S
        Applied logistic regression. John Wiley & Sons, New York, NY2000 (2nd ed.)
        • Rao PV
        Statistical research methods in the life sciences. Brooks/Cole Publishing Company, Pacific Grove, CA1998
      3. SAS Institute Inc.
        SAS/STAT 9.1 user's guide. 2004; (SAS Institute Inc. Cary, NC:)
        • Klein JP
        • Moeschberger ML
        Survival analysis: techniques for censored and truncated data. Springer-Verlag New York, New York, NY1997
        • Gasse C
        • Hollowell J
        • Meier CR
        • et al.
        Drug interactions and risk of acute bleeding leading to hospitalisation or death in patients with chronic atrial fibrillation treated with warfarin.
        Thromb Haemost. 2005; 94: 537-543
        • Lip GY
        • Varughese GL
        Diabetes mellitus and atrial fibrillation: perspectives on epidemiological and pathophysiological links.
        Int J Cardiol. 2005; 105: 319-321
        • Ostgren CJ
        • Merlo J
        • Rastam L
        • et al.
        Atrial fibrillation and its association with type 2 diabetes and hypertension in a Swedish community.
        Diabetes Obes Metab. 2004; 6: 367-374
        • Di Marco JP
        • Flaker G
        • Waldo AL
        • et al.
        Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.
        Am Heart J. 2005; 149: 650-656
        • McMahan DA
        • Smith DM
        • Carey MA
        • et al.
        Risk of major hemorrhage for outpatients treated with warfarin.
        J Gen Intern Med. 1998; 13: 311-316
        • White RH
        • Beyth RJ
        • Zhou H
        • et al.
        Major bleeding after hospitalization for deep-venous thrombosis.
        Am J Med. 1999; 107: 414-424
        • Steffensen FH
        • Kristensen K
        • Ejlersen E
        • et al.
        Major haemorrhagic complications during oral anticoagulant therapy in a Danish population-based cohort.
        J Intern Med. 1997; 242: 497-503
        • Matchar DB
        • Samsa GP
        Secondary and tertiary prevention of stroke: patient outcomes research team; excerpts, seventh progress report. 1995; (Center for Health Policy Research and Education, Duke University. Durham, NC:)
        • Albers GW
        • Dalen JE
        • Laupacis A
        • et al.
        Antithrombotic therapy in atrial fibrillation.
        Chest. 2001; 119: 194S-206S
        • Lip GYH
        • Zarifis J
        • Watson RDS
        • et al.
        Physician variation in the management of patients with atrial fibrillation.
        Heart. 1996; 75: 200-205