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Fecal Hemoglobin Excretion in Elderly Patients With Atrial Fibrillation: Combined Aspirin and Low-Dose Warfarin vs Conventional Warfarin Therapy

Fecal Hemoglobin Excretion in Elderly Patients With Atrial Fibrillation: Combined Aspirin and... Abstract Background: Antithrombotic prophylaxis using combined aspirin and low-dose warfarin is under evaluation in several clinical trials. However, combination therapy may result in increased gastrointestinal blood loss and clinical bleeding vs conventional single-agent antithrombotic therapy. Methods: To assess differences in gastrointestinal blood loss, we measured quantitative fecal hemoglobin equivalents (HemoQuant, Mayo Medical Laboratory, Rochester, Minn) in 117 patients, mean age 71 years, 1 month after initiation of assigned therapy in the Stroke Prevention in Atrial Fibrillation III Study. Sixty-three of these patients who had characteristics for high risk of stroke were randomly assigned to conventional adjusted-dose warfarin therapy (international normalized ratio, 2.0 to 3.0) or low-dose combined therapy (warfarin [international normalized ratio, <1.5] plus 325 mg/d of entericcoated aspirin). The remaining 54 patients with low risk of stroke received 325 mg/d of enteric-coated aspirin. Results: Among the 63 patients at high risk of stroke, abnormal values (>2 mg of hemoglobin per gram of stool) were detected in 11% and values greater than 4 mg of hemoglobin per gram of stool were found in 8%. Mean (±SD) values were more for those randomly assigned to receive combined therapy (1.7±3.3 mg of hemoglobin per gram of stool vs adjusted-dose warfarin therapy, 1.0± 1.9 mg/g; P=.003). The 54 nonrandomized patients with low risk of stroke receiving aspirin alone had a mean (±SD) Hemo-Quant value of 0.8±0.7 mg of hemoglobin per gram of stool 1 month after entry in the study. Conclusions: Abnormal levels of fecal hemoglobin excretion were common in elderly patients with high risk of atrial fibrillation 1 month after randomization to prophylactic antithrombotic therapy. Combined warfarin and aspirin therapy was associated with greater fecal hemoglobin excretion than standard warfarin therapy, suggesting the potential for increased gastrointestinal hemorrhage.(Arch Intern Med. 1996;156:658-660) References 1. Becker RC, Ansell J. Antithrombotic therapy: an abbreviated reference for clinicians . Arch Intern Med. 1955;155:149-161.Crossref 2. Levine MN, Hirsh J, Landefeld S, Raskob G. Hemorrhagic complications of anticoagulant treatment . Chest. 1992;102:352S-363S.Crossref 3. Stein PD, Alpert JS, Copeland J, Dalen JE, Goldman S, Turpie AGG. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves . Chest. 1992;102:445S-455S.Crossref 4. Meade TW, Howarth DJ, Brennan PJ. Effects of low intensity antithrombotic regimes on the haemoglobin level . Thromb Haemost. 1994;71:284-285. 5. 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.Crossref 6. Landefeld CS, Rosenblatt MW, Goldman L. Bleeding in outpatients treated with warfarin: relation to the prothrombin time and important remediable lesions . Am J Med. 1989;87:153-159.Crossref 7. Second Report of the Sixty Plus Reinfarction Study Research Group. Risks of long-term oral anticoagulant therapy in elderly patients after myocardial infarction . Lancet. 1982;1:64-68. 8. Forfar JC. Prediction of hemorrhage during long-term oral coumarin anticoagulation by excessive prothrombin ratio . Am Heart J. 1982;103:445-446.Crossref 9. Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin . Ann Intern Med. 1994;120:897-902.Crossref 10. Schwartz S, Dahl J, Ellefson M, Ahlquist DA. The HemoQuant test: a specific and quantitative determination of heme (hemoglobin) in feces and other materials . Clin Chem. 1983;29:2061-2067. 11. Ahlquist DA, Wiand HS, Moertel CG, et al. Accuracy of fecal occult blood screening for colorectal neoplasia: a prospective study using Hemoccult and Hemo- Quant. JAMA. 1993;269:1262-1267.Crossref 12. Major Ongoing Stroke Trials. Stroke. 1994;25:2112-2116. 13. Turpie AGG, Gent M, Laupacis A, et al. A comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement . N Engl J Med. 1993;329:524-529.Crossref 14. Benjamin EJ, Levy D, Vaziri SM, D'Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort: The Framingham Heart Study . JAMA. 1994;271:840-844.Crossref 15. Atrial Fibrillation Investigators. 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;154:1449-1457.Crossref 16. Wolf PA, Lewis A. Conner Lecture: contributions of epidemiology to the prevention of stroke . Circulation. 1993;88:2471-2478.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Fecal Hemoglobin Excretion in Elderly Patients With Atrial Fibrillation: Combined Aspirin and Low-Dose Warfarin vs Conventional Warfarin Therapy

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Publisher
American Medical Association
Copyright
Copyright © 1996 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1996.00440060086010
Publisher site
See Article on Publisher Site

Abstract

Abstract Background: Antithrombotic prophylaxis using combined aspirin and low-dose warfarin is under evaluation in several clinical trials. However, combination therapy may result in increased gastrointestinal blood loss and clinical bleeding vs conventional single-agent antithrombotic therapy. Methods: To assess differences in gastrointestinal blood loss, we measured quantitative fecal hemoglobin equivalents (HemoQuant, Mayo Medical Laboratory, Rochester, Minn) in 117 patients, mean age 71 years, 1 month after initiation of assigned therapy in the Stroke Prevention in Atrial Fibrillation III Study. Sixty-three of these patients who had characteristics for high risk of stroke were randomly assigned to conventional adjusted-dose warfarin therapy (international normalized ratio, 2.0 to 3.0) or low-dose combined therapy (warfarin [international normalized ratio, <1.5] plus 325 mg/d of entericcoated aspirin). The remaining 54 patients with low risk of stroke received 325 mg/d of enteric-coated aspirin. Results: Among the 63 patients at high risk of stroke, abnormal values (>2 mg of hemoglobin per gram of stool) were detected in 11% and values greater than 4 mg of hemoglobin per gram of stool were found in 8%. Mean (±SD) values were more for those randomly assigned to receive combined therapy (1.7±3.3 mg of hemoglobin per gram of stool vs adjusted-dose warfarin therapy, 1.0± 1.9 mg/g; P=.003). The 54 nonrandomized patients with low risk of stroke receiving aspirin alone had a mean (±SD) Hemo-Quant value of 0.8±0.7 mg of hemoglobin per gram of stool 1 month after entry in the study. Conclusions: Abnormal levels of fecal hemoglobin excretion were common in elderly patients with high risk of atrial fibrillation 1 month after randomization to prophylactic antithrombotic therapy. Combined warfarin and aspirin therapy was associated with greater fecal hemoglobin excretion than standard warfarin therapy, suggesting the potential for increased gastrointestinal hemorrhage.(Arch Intern Med. 1996;156:658-660) References 1. Becker RC, Ansell J. Antithrombotic therapy: an abbreviated reference for clinicians . Arch Intern Med. 1955;155:149-161.Crossref 2. Levine MN, Hirsh J, Landefeld S, Raskob G. Hemorrhagic complications of anticoagulant treatment . Chest. 1992;102:352S-363S.Crossref 3. Stein PD, Alpert JS, Copeland J, Dalen JE, Goldman S, Turpie AGG. Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves . Chest. 1992;102:445S-455S.Crossref 4. Meade TW, Howarth DJ, Brennan PJ. Effects of low intensity antithrombotic regimes on the haemoglobin level . Thromb Haemost. 1994;71:284-285. 5. 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.Crossref 6. Landefeld CS, Rosenblatt MW, Goldman L. Bleeding in outpatients treated with warfarin: relation to the prothrombin time and important remediable lesions . Am J Med. 1989;87:153-159.Crossref 7. Second Report of the Sixty Plus Reinfarction Study Research Group. Risks of long-term oral anticoagulant therapy in elderly patients after myocardial infarction . Lancet. 1982;1:64-68. 8. Forfar JC. Prediction of hemorrhage during long-term oral coumarin anticoagulation by excessive prothrombin ratio . Am Heart J. 1982;103:445-446.Crossref 9. Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin . Ann Intern Med. 1994;120:897-902.Crossref 10. Schwartz S, Dahl J, Ellefson M, Ahlquist DA. The HemoQuant test: a specific and quantitative determination of heme (hemoglobin) in feces and other materials . Clin Chem. 1983;29:2061-2067. 11. Ahlquist DA, Wiand HS, Moertel CG, et al. Accuracy of fecal occult blood screening for colorectal neoplasia: a prospective study using Hemoccult and Hemo- Quant. JAMA. 1993;269:1262-1267.Crossref 12. Major Ongoing Stroke Trials. Stroke. 1994;25:2112-2116. 13. Turpie AGG, Gent M, Laupacis A, et al. A comparison of aspirin with placebo in patients treated with warfarin after heart-valve replacement . N Engl J Med. 1993;329:524-529.Crossref 14. Benjamin EJ, Levy D, Vaziri SM, D'Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort: The Framingham Heart Study . JAMA. 1994;271:840-844.Crossref 15. Atrial Fibrillation Investigators. 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;154:1449-1457.Crossref 16. Wolf PA, Lewis A. Conner Lecture: contributions of epidemiology to the prevention of stroke . Circulation. 1993;88:2471-2478.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Mar 25, 1996

References