Antithrombotic prophylaxis - treatment according to guidelines or according to the patient's needs ?

Implementing the knowledge of pharmacogenetics into the treatment of cardiovascular diseases has moved from the phase of theoretical

assumptions to that of practical use, which is particularly true for antithrombotic treatment. Polymorphism of transformation

enzymes, the transport systems governing the fate of drugs in the organism, as well as of receptors, enzymes or signalling molecules

affecting drug action usually underlies the interindividual differences in the effects of drugs. In antithrombotic treatment, polymorphism

of transport proteins (P-glycoprotein) in resorption or polymorphism of CYP2C19 isoenzyme involved in clopidogrel bioactivation, in

particular, are of clinical significance. P-glycoprotein (P-gp) genotyping is important in order to determine the bioavailability of clopidogrel;

the 3435CC genotype is associated with low P-gp activity and with a higher bioavailability of clopidogrel, thus with a more re liable

antithrombotic effect. The determination of the CYP2C19 genotype, particularly of CYP2C19*2 or CYP2C19*3, is also of importance;

clopidogrel bioactivation is slower in carriers of these alleles and more of the prodrug is degraded by esterases. Similarly, genotyping of

vitamin K reductase and CYP2C9 which determine the effect and speed of biodegradation of warfarin is important in persons at risk.

Keywords: polymorphism, clopidogrel, warfarin, CYP isoenzymes, transport proteins, pharmacogenetics