Journal «Angiology and Vascular Surgery» • 

2016 • VOLUME 22 • №4

Algorithm for selection of individual therapy with clopidogrel in vascular surgical practice

Shevela A.I., Slepukhina A.A., Zelenskaya E.M., Seredina T.A., Lifshits G.I.

Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia

For treatment of patients with diseases of lower limb arteries and prevention of cardiovascular complications in high-risk patients (those with diabetes mellitus, arterial hypertension, dyslipidemia, obesity) permanent antiplatelet therapy is indicated. A problem is variable individual sensitivity to therapeutic agents. For antiplatelet therapy in patients with atherosclerosis of lower limb arteries there has been obtained an evidence-supported base concerning efficacy of long-term administration of clopidogrel preparations, unlike patients with acute coronary syndrome, for whom there has been accumulated an evidence-confirmed base of administering clopidogrel preparations, as well as ticagrelor and prasugrel in various clinical situations.

Clopidogrel is currently the best known representative from the group of thienopyridines. It is a pro-drug and has complicated metabolism: two-stage oxidation under the effect of isoforms of cytochrome 2C19. Its active form irreversibly inhibits binding of ADP with P2Y12 receptors of thrombocytes. This is followed by inhibition of binding of fibrinogen with the glycoprotein IIb/IIIa receptor and a decrease of aggregation. Determining blood platelet aggregation with ADP, collagen and arachidonic acid forms the basis of clinical assessment of the functional state of thrombocytic activity and may be a marker of efficacy of treatment with antiaggregants. A complicated mechanism of action of clopidogrel implies individual policy of the attending physician in making a decision concerning the duration of therapy and selection of the dose. These prerequisites resulted in working out a recommended algorithm of individual dosing of clopidogrel (based on the analysis of case histories of patients with atherosclerosis of lower limb arteries by the level of platelet aggregation to a series of inducers) and correction of the dose of the drug based on the results of molecular-genetic testing of the cytochrome CYPC19 gene. The algorithm makes it possible to achieve a maximum level of efficacy and safety of treatment with antiaggregants.

KEY WORDS: atherosclerosis of lower limb arteries, clopidogrel, aspirin, CYP2C19, vascular surgery, antiaggregant therapy, intermittent claudication, resistance to aspirin, resistance to clopidogrel.

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