Pharmacogenomic considerations for antiplatelet agents: the era of precision medicine in stroke prevention and neurointerventional practice

Cold Spring Harb Mol Case Stud. 2019 Apr 1;5(2):a003731. doi: 10.1101/mcs.a003731. Print 2019 Apr.

Abstract

Antiplatelet drugs are widely utilized in the setting of primary stroke prevention, secondary stroke prevention, and neuroendovascular device-related stroke prevention. These medications are effective in general, although significant variability in drug activity exists between patients. Although this variation may be related in part to a multitude of factors, a growing body of evidence suggests that individual genotypes are a main contributor. The PharmGKB database was mined to prioritize genetic variants with potential clinical relevance for response to aspirin, clopidogrel, prasugrel, and ticagrelor. Although variants were reported for all drugs, the highest level of evidence was found in cytochrome P450 (CYP450) genotype variation related to clopidogrel response. Individual genetic influences have an impact on the pharmacodynamics of antiplatelet agents. Current clinical practice for stroke prevention is primarily empiric or guided by functional assays; however, there now exists a third potential pathway to base treatment decisions: genotype-guided treatment.

Publication types

  • Review

MeSH terms

  • Clopidogrel / pharmacokinetics
  • Clopidogrel / therapeutic use
  • Cytochrome P-450 Enzyme System / genetics
  • Humans
  • Pharmacogenomic Variants*
  • Platelet Aggregation Inhibitors / pharmacokinetics*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prasugrel Hydrochloride / pharmacokinetics
  • Prasugrel Hydrochloride / therapeutic use
  • Precision Medicine
  • Stroke / genetics
  • Stroke / prevention & control*
  • Ticagrelor / pharmacokinetics
  • Ticagrelor / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Cytochrome P-450 Enzyme System
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticagrelor