Dosing Algorithms to Predict Warfarin Maintenance Dose in Caucasians and African Americans

Abstract

Objectives-The objective of this study was to determine whether clinical, environmental, and genetic factors can be used to develop dosing algorithms for Caucasians and African Americans that perform better than giving empirical 5 mg/day. Methods-From April 2002 through December 2005, 259 warfarin initiators were prospectively followed until they reached maintenance dose.Results-The Caucasian algorithm included 11 variables (R 2 =0.43). This model (51% within 1 mg) performed better compared with 5 mg/day (29% within 5±1 mg). The African American algorithm included 10 variables (R 2 =0.28). This model predicted 37% of doses within 1 mg of the observed dose; a small improvement compared with 5 mg/day (34%). These results were similar to the results we obtained from testing other (published) algorithms.Conclusions-The dosing algorithms in Caucasians explained <45% of the variability and the algorithms in African Americans performed only marginally better than giving 5 mg empirically.

Prevalence of genetic polymorphisms of CYP2C9 and VKORC1 — Implications for warfarin management and outcome in Croatian patients with acute stroke

“…In Croatian population, the prevalence of variant CYP2C9*2 and *3 alleles is estimated to be 35% (Božina), which is similar to some other data published for Caucasians (41,43).…”

“…Studies of inter-ethnic differences in sensitivity to warfarin confirmed that the VKORC1 polymorphism had significantly greater influence on the variability of dose in Asians and Caucasians than in Afro-Americans as the result of race-specific differences in the frequency of VKORC1 polymorphisms (40)(41)(42)(43). A studies conducted confirmed that this is due to differences in MAFs (minor allele frequency) across racial groups.…”

Warfarin pharmacogenetics: development of a dosing algorithm for Omani patients

“…9,16,22 Furthermore, three genome-wide association studies failed to find any additional genetic loci other than those herein studied (CYP2C9, CYP4F2 and VKORC1) with regard to influence on warfarin dose requirement. 23,24 In conclusion, in this first report on the impact of genetic, clinical and demographic factors involved in warfarin dose requirement in the Omani patients, a significant percentage of variability still (around 37%) awaits explanation.…”

“…Limdi et al, 1 in a recent study demonstrated that VKORC1 3673G4A polymorphism was predictive of warfarin dose across three racial groups, namely Asians, Blacks and Whites, but its contribution varies between 11 and 32% amongst Caucasians, 30% in Asians and 4-10% in African Americans, reflecting its relative frequency in each population. 9,10,15,16 28 (20) 17 (24) n.s.…”

“…9,15 Contribution of the CYP2C9 variant alleles to warfarin dose variability differed widely across geographical groups collectively classified as Whites (2.5-18.3 mg per day). 10,11,15,16 Lee et al, 17 in a study from Singapore, showed that the CYP2C9 genotype accounted for 29, 7 and 0% of warfarin dose variance among Indians, Chinese and Malay patients, respectively. Cavallari et al 9 reported that the influence of CYP2C9 variant alleles on warfarin dose was around 15% in a predominantly African American population and inclusion of the CYP2C9*5, *6, *8 and *11 alleles further improved the predictive ability beyond that seen with CYP2C9*2 and *3.…”