Clopidogrel and warfarin pharmacogenetic tests: what is the evidence for use in clinical practice?

Abstract

Purpose of review: To review the most promising genetic markers associated with the variability in the safety or efficacy of warfarin and clopidogrel and highlight the verification and validation initiatives for translating clopidogrel and warfarin pharmacogenetic tests to clinical practice.

Recent findings: Rapid advances in pharmacogenetics, continuous decrease in genotyping cost, development of point-of-care devices and the newly established clinical genotyping programs at several institutions hold the promise of individualizing clopidogrel and warfarin based on genotype. Guidelines have been established to assist clinicians in prescribing clopidogrel or warfarin dose based on genotype. However, the clinical utility of clopidogrel and warfarin is still limited. Accordingly, large randomized clinical trials are underway to define the role of clopidogrel and warfarin pharmacogenetics in clinical practice.

Summary: Pharmacogenetics has offered compelling evidence toward the individualization of clopidogrel and warfarin therapies. The rapid advances in technology make the clinical implementation of clopidogrel and warfarin pharmacogenetics possible. The clinical genotyping programs and the ongoing clinical trials will help in overcoming some of the barriers facing the clinical implementation of clopidogrel and warfarin pharmacogenetics.

FIGURE 1

Clopidogrel pharmacokinetics and pharmacodynamics.

FIGURE 2

Evidence-based clopidogrel dosing based on CYP2C19 genotype in acute coronary syndrome / percutaneous coronary intervention patients (ACS/PCI), adapted from CPIC guidelines [44▪▪] with revisions based on more recent literature. UM, ultra metabolizer; EM, extensive metabolizer; IM, intensive metabolizer; PM, poor metabolizer. ^aIt is preferable to use the alternative antiplatelet (prasugrel or ticagrelor) as a first option unless there are any contraindications to its use. Giving a clopidogrel dose of 225 mg per day to CYP2C19*2 heterozygote carriers was reported to be sufficient for getting similar levels of platelet reactivity achieved by noncarriers taking 75 mg per day of clopidogrel [74▪]. However, further studies are still needed to confirm this finding.

FIGURE 3

Status of clopidogrel and warfarin pharmacogenetics: from identification toward clinical implementation. GWAS, genome-wide association studies.