title: Warfarin maintenance dose in older patients: higher average dose and wider dose frequency distribution in patients of African ancestry than those of European ancestry.
abstract: Studies report that warfarin doses required to maintain therapeutic anticoagulation decrease with age; however, these studies almost exclusively enrolled patients of European ancestry. Consequently, universal application of dosing paradigms based on such evidence may be confounded because ethnicity also influences dose. Therefore, we determined if warfarin dose decreased with age in Americans of African ancestry, if older African and European ancestry patients required different doses, and if their daily dose frequency distributions differed. Our chart review examined 170 patients of African ancestry and 49 patients of European ancestry cared for in our anticoagulation clinic. We calculated the average weekly dose required for each stable, anticoagulated patient to maintain an international normalized ratio of 2.0 to 3.0, determined dose averages for groups <70, 70-79, and >80 years of age and plotted dose as a function of age. The maintenance dose in patients of African ancestry decreased with age (P<0.001). In addition, older patients of African ancestry required higher average weekly doses than patients of European ancestry: 33% higher in the 70- to 79-year-old group (38.2+/-1.9 vs. 28.8+/-1.7 mg; P=0.006) and 52% in the >80-year-old group (33.2+/-1.7 vs. 21.8+/-3.8 mg; P=0.011). Therefore, 43% of older patients of African ancestry required daily doses >5mg and hence would have been under-dosed using current starting-dose guidelines. The dose frequency distribution was wider for older patients of African ancestry compared to those of European ancestry (P<0.01). The higher doses required by older patients of African ancestry indicate that strategies for initiating warfarin therapy based on studies of patients of European ancestry could result in insufficient anticoagulation and thereby potentially increase their thromboembolism risk.
authors.affiliation: Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA. cgarwood@wayne.edu
authors.forename: Candice L
authors.initials: CL
authors.lastname: Garwood
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Clemente
authors.forename: George N
authors.initials: GN
authors.lastname: Ibe
authors.forename: Vijay A
authors.initials: VA
authors.lastname: Kandula
authors.forename: Kristy D
authors.initials: KD
authors.lastname: Curtis
authors.forename: Peter
authors.initials: P
authors.lastname: Whittaker
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D044383:Black People; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014859:Warfarin / Q000008:administration & dosage* / Q000627:therapeutic use; D044465:White People
chemical_list: D000925:Anticoagulants; D014859:Warfarin