Warfarin maintenance dose in older patients: Higher average dose and wider dose frequency distribution in patients of African ancestry than those of European ancestry

Garwood, Candice L.; Clemente, Jennifer L.; Ibe, George N.; Kandula, Vijay A.; Curtis, Kristy D.; Whittaker, Peter

doi:10.1016/j.bcmd.2010.03.006

Cited by 12 publications

(11 citation statements)

References 22 publications

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“…We and others have shown that maintenance dose variability is as marked in older patients as in younger patients (i.e. 15-to 20fold) [1,18,25]. The characteristics of our study participants were representative of frail elderly inpatients, with a mean age of 85 years, substantial comorbidities, and numerous concomitant medications.…”

Section: Discussionmentioning

confidence: 99%

Predicting the warfarin maintenance dose in elderly inpatients at treatment initiation: accuracy of dosing algorithms incorporating or not VKORC1/CYP2C9 genotypes

Moreau

Pautas

Gouin‐Thibault

et al. 2011

Journal of Thrombosis and Haemostasis

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Summary. Background: Initiating warfarin is challenging in frail elderly patients because of low-dose requirements and interindividual variability. Objectives: We investigated whether incorporating VKORC1 and CYP2C9 genotype information in different models helped to predict the warfarin maintenance dose when added to clinical data and INR values at baseline (Day 0), and during warfarin induction. Patients: We prospectively enrolled 187 elderly inpatients (mean age, 85.6 years), all starting on warfarin using the same Ôgeriatric dosing-algorithmÕ based on the INR value measured on the day after three 4-mg warfarin doses (INR 3 ) and on INR 6 ± 1 . Results: On Day 0, the clinical model failed to accurately predict the maintenance dose (R 2 < 0.10). Adding the VKORC1 and CYP2C9 genotypes to the model increased R 2 to 0.31. On Day 3, the INR 3 value was the strongest predictor, completely embedding the VKORC1 genotype, whereas the CYP2C9 genotype remained a significant predictor (model-R 2 0.55). On Day 6 ± 1, none of the genotypes predicted the maintenance dose. Finally, the simple Ôgeriatric dosing-algorithmÕ was the most accurate algorithm on Day 3 (R 2 0.77) and Day 6 (R 2 0.81), underestimating ( ‡ 1 mg) and over-estimating the dose ( ‡ 1 mg) in fewer than 10% and 2% of patients, respectively. Clinical models and the Ôgeriatric dosing-algorithmÕ were validated on an independent sample. Conclusions: Before starting warfarin therapy, the VKORC1 genotype is the best predictor of the maintenance dose. Once treatment is started using induction doses tailored for elderly patients, the contribution of VKORC1 and CYP2C9 genotypes in dose refinement is negligible compared with two INR values measured during the first week of treatment.

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Section: Discussionmentioning

confidence: 99%

Predicting the warfarin maintenance dose in elderly inpatients at treatment initiation: accuracy of dosing algorithms incorporating or not VKORC1/CYP2C9 genotypes

Moreau

Pautas

Gouin‐Thibault

et al. 2011

Journal of Thrombosis and Haemostasis

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“…For example, our patients were almost exclusively of African ancestry, a population typically associated with higher warfarin dose requirement than patients of European ancestry. 10,14 In contrast, slightly more than one-half of the patients in 1 of these prior studies were of African ancestry; however, they were not evenly distributed among the groups. Kidney Disease, Anticoagulation Stability, and the Effect on Patient Management Kidney disease was associated with decreased anticoagulation stability, indicated by the significant decrease in TTR and the proportion of visits at which INR was within the target range versus the comparison group.…”

Section: Kidney Disease and Warfarin Dosementioning

confidence: 91%

“…We selected patients from a database (n = 219) compiled for a previous study. 10 This database included patients who had an INR target range of 2.0-3.0, were older than 18 years, had attended the clinic for more than 3 months, and had at least 8 visits after achievement of therapeutic anticoagulation (defined as 2 consecutive INRs within target range). Patients treated with amiodarone, which has a well-established and large effect on warfarin dose, and patients who required dialysis were excluded from the database.…”

Section: What Is Already Known About This Subjectmentioning

confidence: 99%

Effect of Chronic Kidney Disease on Warfarin Management in a Pharmacist-Managed Anticoagulation Clinic

Kleinow¹,

Garwood²,

Clemente³

et al. 2011

JMCP

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“… 47 A chart review comparing older African-American and Caucasian patients found that although the dose of warfarin required to maintain a therapeutic INR decreased with age, African-Americans required a higher maintenance dose than Caucasians. 48 Therefore, strategies for initiating warfarin therapy based on studies of patients of European ancestry could result in insufficient anticoagulation of older African-American patients, thereby potentially increasing their risk of thromboembolism. 48 …”

Section: Differences In Treatment By Race/ethnicitymentioning

confidence: 99%

Use of oral anticoagulants in African-American and Caucasian patients with atrial fibrillation: is there a treatment disparity?

Akinboboye¹

2015

JMDH

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Atrial fibrillation (AF) is a very common cardiac arrhythmia, and its prevalence is increasing along with aging in the developed world. This review discusses racial differences in the epidemiology and treatment of AF between African-American and Caucasian patients. Additionally, the effect of race on warfarin and novel oral anticoagulant use is discussed, as well as the role that physicians and patients play in achieving optimal treatment outcomes. Despite having a lower prevalence of AF compared with Caucasians, African-Americans suffer disproportionately from stroke and its sequelae. The possible reasons for this paradox include poorer access to health care, lower health literacy, and a higher prevalence of other stroke-risk factors among African-Americans. Consequently, it is important for providers to evaluate the effects of race, health literacy, access to health care, and cultural barriers on the use of anticoagulation in the management of AF. Warfarin-dose requirements vary across racial groups, with African-American patients requiring a higher dose than Caucasians to maintain a therapeutic international normalized ratio; the novel oral anticoagulants (dabigatran, rivaroxaban, and apixaban) seem to differ in this regard, although data are currently limited. Minority racial groups are not proportionally represented in either real-world studies or clinical trials, but as more information becomes available and other social issues are addressed, the treatment disparities between African-American and Caucasian patients should decrease.

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Warfarin maintenance dose in older patients: Higher average dose and wider dose frequency distribution in patients of African ancestry than those of European ancestry

Cited by 12 publications

References 22 publications

Predicting the warfarin maintenance dose in elderly inpatients at treatment initiation: accuracy of dosing algorithms incorporating or not VKORC1/CYP2C9 genotypes

Predicting the warfarin maintenance dose in elderly inpatients at treatment initiation: accuracy of dosing algorithms incorporating or not VKORC1/CYP2C9 genotypes

Effect of Chronic Kidney Disease on Warfarin Management in a Pharmacist-Managed Anticoagulation Clinic

Use of oral anticoagulants in African-American and Caucasian patients with atrial fibrillation: is there a treatment disparity?

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