Racial and ethnic differences in warfarin response

Abstract

Background and aim of the study: Variability of drug response among individuals is a well-recognized problem that may result in either under- or overtreatment of patients receiving similar drug concentrations. Patients with mechanical heart valves are dependent on adequate anticoagulation to prevent thrombosis development. 'Crystalline warfarin sodium' (warfarin) is the most common antithrombotic drug prescribed to control blood hemostasis in those patients, and also in those with indications such as stroke, myocardial infarction, pulmonary embolism and atrial fibrillation. Warfarin is a narrow therapeutic index agent; a small change in systemic concentration of the drug may lead to significant changes in pharmacodynamic response. Careful clinical management is required to balance the risks of bleeding (over-anticoagulation) with those of thrombosis (under-anticoagulation). The study aim was to summarize environmental, genetic and ethnic factors that affect a patient's response to warfarin and which must be considered for optimal patient outcome.

Methods: A Medline search was carried out to summarize various factors that influence a patient's response to warfarin.

Results: Inter-ethnic differences may have profound implications for the efficacy and safety of warfarin. Ethnic differences can affect pharmacokinetic features such as bioavailability, protein binding and volume of distribution, as well as hepatic metabolism and renal elimination. Environmental factors and genetic variants in human enzymes that metabolize warfarin also contribute to interindividual variations and may render some patients more susceptible to serious or life-threatening adverse events.

Conclusion: Warfarin use is complicated by an unpredictable dose response that depends on factors such as demographics, diet, interacting drugs, genetic polymorphism and ethnic differences. The impact of racial differences on the kinetics of dose response or on drug efficacy is not well defined, as few clinical trials take ethnic variation into account. The use of the point of care and frequent patient self-testing may permit standardized warfarin monitoring across diverse geographical regions and facilitate analysis of ethnic variation among subpopulations.