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Pharmacogenetic and Clinical Predictors of Clopidogrel Insufficiency in a Patient with Atherosclerosis Obliterans of the Lower Extremities: Clinical Case

https://doi.org/10.20996/1819-6446-2018-14-5-699-702

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Abstract

The considered clinical case of combination of multifocal atherosclerotic vascular lesion with type 2 diabetes mellitus and liver fibrosis demonstrates a combination of polyvalent risk factors  for resistance to antiplatelet therapy with clopidogrel. The decrease in the effectiveness of prolonged therapy with P2Y12  inhibitor was clinically manifested by repeated thrombotic events and was confirmed by laboratorial VerifyNow P2Y12  Assay test system as a low percentage of inhibition of ADP-induced platelet aggregation. We established probable genetic predictors of the decrease in the effectiveness of antiplatelet therapy in this patient, namely, the  carriage of polymorphic markers  of the  ABCB1 CT, CES1 CA and  CYP3A4*22 CT genes  that determine the decrease in absorption, excessive hydrolysis of the drug and reduced activity of isoenzymes and transporters, that leads to disorders of active clopidogrel metabolite formation. A potential contribution of hepatic dysfunction to reduction in antiaggregant effect of P2Y12 inhibitor was demonstrated. Variant of drug interaction of clopidogrel and an inhibitor/substrate of P450 CYP2C19 – omeprazole, accompanied by a decrease in the effectiveness of antiplatelet therapy, was also considered.

About the Authors

M. A. Andreyanova
Russian Medical Academy of Continuous Professional Education
Russian Federation

Maria A. Andreyanova – MD, Assistant, Chair of Therapy and Adolescent Medicine.

Barrikadnaya ul. 2/1, Moscow, 123995.

 



K. B. Mirzaev
Russian Medical Academy of Continuous Professional Education
Russian Federation

Karin B. Mirzaev – MD, PhD, Junior Researcher,  Group of Clinico-Pharmacological Technologies, Research Center.

Barrikadnaya ul. 2/1, Moscow, 123995.

 



D. A. Sychev
Russian Medical Academy of Continuous Professional Education
Russian Federation

Dmitry A. Sychev – MD, PhD, Professor, Corresponding Member of the Russian Academy of Sciences, Head of Chair of Clinical Pharmacology and Therapy; Leading Researcher,  Group of Clinico-Pharmacological Technologies, Research Center.

Barrikadnaya ul. 2/1, Moscow, 123995.

 



K. A. Ryzhikova
Russian Medical Academy of Continuous Professional Education
Russian Federation

Kristina A. Ryzhikova – Junior Researcher,  Group of Clinico-Pharmacological Technologies, Research Center.

Barrikadnaya ul. 2/1, Moscow, 123995.

 



A. V. Pokrovsky
A.V. Vishnevsky Institute of Surgery
Russian Federation

Alexander V. Pokrovsky – MD, PhD, Professor, Head of Department of Cardiovascular Surgery.

Bolshaya Serpukhovskaya ul. 27,  Moscow, 117997.

 



A. F. Kharazov
A.V. Vishnevsky Institute of Surgery
Russian Federation

Alexander F. Kharazov – MD, PhD, Associate Professor, Senior Researcher.

Bolshaya Serpukhovskaya ul. 27,  Moscow, 117997.

 



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For citation:


Andreyanova M.A., Mirzaev K.B., Sychev D.A., Ryzhikova K.A., Pokrovsky A.V., Kharazov A.F. Pharmacogenetic and Clinical Predictors of Clopidogrel Insufficiency in a Patient with Atherosclerosis Obliterans of the Lower Extremities: Clinical Case. Rational Pharmacotherapy in Cardiology. 2018;14(5):699-702. (In Russ.) https://doi.org/10.20996/1819-6446-2018-14-5-699-702

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)