Stratifying the risks of oral anticoagulation in patients with liver disease.
BACKGROUND
Chronic liver disease presents a relative contraindication to warfarin therapy, but some patients with liver disease nevertheless require long-term anticoagulation. The goal is to identify which patients with liver disease might safely receive warfarin.


RESULTS
Among 102 134 patients who received warfarin from the Veterans Affairs from 2007 to 2008, International Classification of Diseases-Ninth Revision codes identified 1763 patients with chronic liver disease. Specific diagnoses and laboratory values (albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and cholesterol) were examined to identify risk of adverse outcomes, while controlling for available bleeding risk factors. Outcomes included percent time in therapeutic range, a measure of anticoagulation control, and major hemorrhagic events, by International Classification of Diseases-Ninth Revision codes. Patients with liver disease had lower mean time in therapeutic range (53.5%) when compared with patients without (61.7%; P<0.001) and more hemorrhages (hazard ratio, 2.02; P<0.001). Among patients with liver disease, serum albumin and creatinine levels were the strongest predictors of both outcomes. We created a 4-point score system: patients received 1 point each for albumin (2.5-3.49 g/dL) or creatinine (1.01-1.99 mg/dL), and 2 points each for albumin (<2.5 g/dL) or creatinine (≥2 mg/dL). This score predicted both anticoagulation control and hemorrhage. When compared with patients without liver disease, those with a score of zero had modestly lower time in therapeutic range (56.7%) and no increase in hemorrhages (hazard ratio, 1.16; P=0.59), whereas those with the worst score (4) had poor control (29.4%) and high hazard of hemorrhage (hazard ratio, 8.53; P<0.001).


CONCLUSIONS
Patients with liver disease receiving warfarin have poorer anticoagulation control and more hemorrhages. A simple 4-point scoring system using albumin and creatinine identifies those at risk for poor outcomes.
From the Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial VA Medical Center, Bedford, MA (D.R.B., A.S.A., E.M.H., A.O., J.I.R., S.Z., G.K.J., A.J.R.); Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, MA (L.M.E., D.R.B., A.S.A., E.M.H., A.J.R.); Section of Gastroenterology, Granite Medical Group, Boston University Medical Center, MA (D.S.M.); Department of Health Policy and Management, Boston University School of Public Health, MA (D.R.B., G.K.J.); Division of Biostatistics and Health Services Research, Department of Quantitative Health Sciences, University of Massachusetts School of Medicine, Worcester (A.S.A.); and Biostatistics Section, Boston Children's Hospital, MA (A.O.). lydefi@gmail.com.
Lydia M
LM
Efird
From the Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial VA Medical Center, Bedford, MA (D.R.B., A.S.A., E.M.H., A.O., J.I.R., S.Z., G.K.J., A.J.R.); Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, MA (L.M.E., D.R.B., A.S.A., E.M.H., A.J.R.); Section of Gastroenterology, Granite Medical Group, Boston University Medical Center, MA (D.S.M.); Department of Health Policy and Management, Boston University School of Public Health, MA (D.R.B., G.K.J.); Division of Biostatistics and Health Services Research, Department of Quantitative Health Sciences, University of Massachusetts School of Medicine, Worcester (A.S.A.); and Biostatistics Section, Boston Children's Hospital, MA (A.O.).
Daniel S
DS
Mishkin
From the Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial VA Medical Center, Bedford, MA (D.R.B., A.S.A., E.M.H., A.O., J.I.R., S.Z., G.K.J., A.J.R.); Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, MA (L.M.E., D.R.B., A.S.A., E.M.H., A.J.R.); Section of Gastroenterology, Granite Medical Group, Boston University Medical Center, MA (D.S.M.); Department of Health Policy and Management, Boston University School of Public Health, MA (D.R.B., G.K.J.); Division of Biostatistics and Health Services Research, Department of Quantitative Health Sciences, University of Massachusetts School of Medicine, Worcester (A.S.A.); and Biostatistics Section, Boston Children's Hospital, MA (A.O.).
Dan R
DR
Berlowitz
From the Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial VA Medical Center, Bedford, MA (D.R.B., A.S.A., E.M.H., A.O., J.I.R., S.Z., G.K.J., A.J.R.); Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, MA (L.M.E., D.R.B., A.S.A., E.M.H., A.J.R.); Section of Gastroenterology, Granite Medical Group, Boston University Medical Center, MA (D.S.M.); Department of Health Policy and Management, Boston University School of Public Health, MA (D.R.B., G.K.J.); Division of Biostatistics and Health Services Research, Department of Quantitative Health Sciences, University of Massachusetts School of Medicine, Worcester (A.S.A.); and Biostatistics Section, Boston Children's Hospital, MA (A.O.).
Arlene S
AS
Ash
From the Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial VA Medical Center, Bedford, MA (D.R.B., A.S.A., E.M.H., A.O., J.I.R., S.Z., G.K.J., A.J.R.); Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, MA (L.M.E., D.R.B., A.S.A., E.M.H., A.J.R.); Section of Gastroenterology, Granite Medical Group, Boston University Medical Center, MA (D.S.M.); Department of Health Policy and Management, Boston University School of Public Health, MA (D.R.B., G.K.J.); Division of Biostatistics and Health Services Research, Department of Quantitative Health Sciences, University of Massachusetts School of Medicine, Worcester (A.S.A.); and Biostatistics Section, Boston Children's Hospital, MA (A.O.).
Elaine M
EM
Hylek
From the Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial VA Medical Center, Bedford, MA (D.R.B., A.S.A., E.M.H., A.O., J.I.R., S.Z., G.K.J., A.J.R.); Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, MA (L.M.E., D.R.B., A.S.A., E.M.H., A.J.R.); Section of Gastroenterology, Granite Medical Group, Boston University Medical Center, MA (D.S.M.); Department of Health Policy and Management, Boston University School of Public Health, MA (D.R.B., G.K.J.); Division of Biostatistics and Health Services Research, Department of Quantitative Health Sciences, University of Massachusetts School of Medicine, Worcester (A.S.A.); and Biostatistics Section, Boston Children's Hospital, MA (A.O.).
Al
A
Ozonoff
From the Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial VA Medical Center, Bedford, MA (D.R.B., A.S.A., E.M.H., A.O., J.I.R., S.Z., G.K.J., A.J.R.); Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, MA (L.M.E., D.R.B., A.S.A., E.M.H., A.J.R.); Section of Gastroenterology, Granite Medical Group, Boston University Medical Center, MA (D.S.M.); Department of Health Policy and Management, Boston University School of Public Health, MA (D.R.B., G.K.J.); Division of Biostatistics and Health Services Research, Department of Quantitative Health Sciences, University of Massachusetts School of Medicine, Worcester (A.S.A.); and Biostatistics Section, Boston Children's Hospital, MA (A.O.).
Joel I
JI
Reisman
From the Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial VA Medical Center, Bedford, MA (D.R.B., A.S.A., E.M.H., A.O., J.I.R., S.Z., G.K.J., A.J.R.); Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, MA (L.M.E., D.R.B., A.S.A., E.M.H., A.J.R.); Section of Gastroenterology, Granite Medical Group, Boston University Medical Center, MA (D.S.M.); Department of Health Policy and Management, Boston University School of Public Health, MA (D.R.B., G.K.J.); Division of Biostatistics and Health Services Research, Department of Quantitative Health Sciences, University of Massachusetts School of Medicine, Worcester (A.S.A.); and Biostatistics Section, Boston Children's Hospital, MA (A.O.).
Shibei
S
Zhao
From the Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial VA Medical Center, Bedford, MA (D.R.B., A.S.A., E.M.H., A.O., J.I.R., S.Z., G.K.J., A.J.R.); Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, MA (L.M.E., D.R.B., A.S.A., E.M.H., A.J.R.); Section of Gastroenterology, Granite Medical Group, Boston University Medical Center, MA (D.S.M.); Department of Health Policy and Management, Boston University School of Public Health, MA (D.R.B., G.K.J.); Division of Biostatistics and Health Services Research, Department of Quantitative Health Sciences, University of Massachusetts School of Medicine, Worcester (A.S.A.); and Biostatistics Section, Boston Children's Hospital, MA (A.O.).
Guneet K
GK
Jasuja
From the Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial VA Medical Center, Bedford, MA (D.R.B., A.S.A., E.M.H., A.O., J.I.R., S.Z., G.K.J., A.J.R.); Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, MA (L.M.E., D.R.B., A.S.A., E.M.H., A.J.R.); Section of Gastroenterology, Granite Medical Group, Boston University Medical Center, MA (D.S.M.); Department of Health Policy and Management, Boston University School of Public Health, MA (D.R.B., G.K.J.); Division of Biostatistics and Health Services Research, Department of Quantitative Health Sciences, University of Massachusetts School of Medicine, Worcester (A.S.A.); and Biostatistics Section, Boston Children's Hospital, MA (A.O.).
Adam J
AJ
Rose
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D005260:Female; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008107:Liver Diseases / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
D000925:Anticoagulants; D012709:Serum Albumin; D014859:Warfarin; D003404:Creatinine
anticoagulants; hemorrhage; liver; warfarin