Clopidogrel (Plavix) is a platelet aggregation inhibitor (TAH) and is used, among other things, for the treatment of coronary disease with acute coronary syndrome and after percutaneous coronary intervention. Clopidogrel is a pro-drug and is only converted into the active active substance by the CYP2C19 enzyme.
Depending on origin, between 18-47% of the population are carriers of at least one CYP2C19 variant, which results in reduced enzyme activity. About 2% of the Caucasian population (about 11% of Asians) are homozygous carriers of a CYP2C19 variant, resulting in a poor metabolizer phenotype (PM) with little to no enzyme activity [1] [2]. Approximately 14% of the Caucasian population (36% in Asians) are heterozygous carriers of a CYP2C19 variant and result in an intermediate metabolizer phenotype (IM) with reduced enzyme activity. CYP2C19 is the main enzyme in the conversion of clopidogrel into the active substance. In CYP2C19 poor metabolizers, there is therefore no or only insufficient inhibition of platelet aggregation, with potentially serious consequences for the patient. Numerous studies have shown the connection between a significantly poorer treatment outcome when using clopidogrel in patients with reduced or absent CYP2C19 enzyme activity. The FDA warns in the prescribing information that clopidogrel is less effective and more likely to cause complications in CYP2C19 poor metabolizers [3].The CPIC (Clinical Pharmacogenetic Implementation Consortium) guidelines recommend the choice of an alternative antiplatelet agent for CYP2C19 IM or PM [1].
- Before starting clopidogrel therapy.
- To clarify molecular causes for the ineffectiveness of clopidogrel therapy.
In CYP2C19 intermediate metabolizers, the dosage should be increased or, if possible, an alternative drug (prasugrel or ticagrelor) should be prescribed. In poor metabolizers, an alternative drug (prasugrel or ticagrelor) should be prescribed if possible.
[1] Simon T, Verstuyft C and Mary-Krause M, "Genetic determinants of response to clopidogrel and cardiovascular events", New England Journal of Medicine, The, vol. 360, no. 4, pp. 363-375, 2 2009. [2] Scott SA, Sangkuhl K and Stein CM, "Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update [review]," Clinical Pharmacology and Therapeutics, vol. 94, no. 3, pp. 317-323, 2013. [3] "PLAVIX- clopidogrel bisulfate tablet, film coated," 10 2018. [Online]. Available: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=01b14603-8f29-4fa3-8d7e-9d523f802e0b [Accessed 25 03 2019]. [4] Claassens DMF, Vos GJA, Bergmeijer TO, "A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI," New England Journal of Medicine, The, vol. 381, no. 17, pp. 1621-1631, 10 2019.
