The genetic basis of antiplatelet and anticoagulant therapy: A pharmacogenetic review of newer antiplatelets (clopidogrel, prasugrel and ticagrelor) and anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban)

ABSTRACT

Introduction: The study of pharmacogenomics presents the possibility of individualised optimisation of drug therapy tailored to each patients’ unique physiological traits. Both antiplatelet and anticoagulant drugs play a key role in the management of cardiovascular disease. Despite their importance, there is a substantial volume of literature to suggest marked person-to-person variability in their effect.

Areas covered: This article reviews the data available for the genetic cause for this inter-patient variability of antiplatelet and anticoagulant drugs. The genetic basis for traditional antiplatelets (i.e. aspirin) is compared with the newly available antiplatelet medicines (clopidogrel, prasugrel and ticagrelor). Similarly, the pharmacogenetics of warfarin is compared with the newer direct oral anticoagulants (DOACs) in detail.

Expert Opinion: We identify strengths and weaknesses in the research thus far; including shortcomings in trial design and a review of newer analytical techniques. The direction of this research and its real-world implications are discussed.

KEYWORDS:

• Pharmacogenetics
• pharmacogenomics
• antiplatelet
• anticoagulant
• DOAC

Article highlights

• Pharmacogenetics is becoming increasingly recognised as a cause for increased or reduced bioavailability of cardiovascular drugs; with significant genetic polymorphisms being mentioned on the summary of product characteristics of clopidogrel and warfarin.

• Aspirin and clopidogrel are the most-studied antiplatelets regarding genetic polymorphisms and centre around either key platelet proteins including cyclooxygenase and platelet glycopeptides, or cytochrome polymorphisms which impact on drug metabolism to a significant degree.

• The Direct Oral Anticoagulants (as well as warfarin) are potentially susceptible to pharmacogenetic variation in their effect. Published literature has identified p-glycopeptide, breast cancer resistance peptide and carboxylesterase-1 (together with cytochrome polymorphisms) as proteins in DOAC metabolism that have the potential to impact bioavailability.

• Newer analytical techniques allow for more accurate and comprehensive genome-wide association which result in variations in drug effect and/or clinical outcome.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded