Racial and ethnic differences in warfarin response

Area of Science:

• Pharmacogenomics
• Clinical Pharmacology
• Drug Metabolism

Background:

• Warfarin (crystalline warfarin sodium) is a critical anticoagulant for patients with mechanical heart valves and other conditions like stroke and atrial fibrillation.
• It is a narrow therapeutic index agent, requiring careful management to avoid bleeding or thrombosis.
• Individual variability in drug response necessitates consideration of various influencing factors for optimal patient outcomes.

Purpose of the Study:

• To summarize environmental, genetic, and ethnic factors impacting patient response to warfarin.
• To highlight the importance of these factors for achieving optimal patient outcomes in warfarin therapy.

Main Methods:

• A comprehensive Medline search was conducted.
• The search focused on identifying factors that influence a patient's response to warfarin.

Main Results:

• Inter-ethnic differences significantly affect warfarin's efficacy and safety by influencing pharmacokinetics (bioavailability, protein binding, metabolism, elimination).
• Environmental factors and genetic variants in warfarin-metabolizing enzymes contribute to interindividual variations, increasing susceptibility to adverse events.
• These variations can lead to unpredictable dose-response relationships.

Conclusions:

• Warfarin therapy is complex due to unpredictable dose responses influenced by demographics, diet, drug interactions, genetic polymorphisms, and ethnic differences.
• Few clinical trials adequately account for ethnic variations, leaving their impact on warfarin kinetics and efficacy not well-defined.
• Point-of-care testing and patient self-monitoring may enable standardized warfarin monitoring and facilitate the analysis of ethnic variations in diverse populations.