Clopidogrel resistance in patients with acute coronary syndrome


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Abstract

Aim: to reveal the frequency of clopidogrel resistance in patients with acute coronary syndrome (ACS) and its impact on prognosis in these patients.
Subjects and methods. Seventy-five clopidogrel-treated patients with ACS were followed up. Optical aggregometry was conducted using ADP 20 μmol. The resistance criteria were baseline platelet aggregation, platelet aggregation on day 7, % < 10%. Inflammatory markers (IL-6, IL-10, and C-reactive protein) were determined. Genetic polymorphisms (the IIIa subunit gene - Leu33Pro, the receptor P2Y12 C18T and G36T gene, and the CYP3*A4(A-293G) gene) were studied.
Results. According to the accepted resistance criteria, 54 (72%) patients were sensitive to clopidogrel and 21 (28%) were resistant to the agent. The resistance was revealed in 7 (23%) of the patients with ECG ST-segment elevation and in 14 (31%) of those with ST-segment elevation. Before admission to the clinic, the unresponsive patients had significantly more frequently received the loading clopidogrel dose of 300 mg while that latter was 600 mg in the responsive patients. As compared with the responsive patients, the unresponsive ones showed a significantly lower baseline antibody level that was increased on day 7. The clopidogrel resistance determined by this criterion had no impact on prognosis. On dividing the patients by aggregation quartile values, poor manifestations insignificantly more frequently occurred in the third and fourth quartiles. No clear correlation was found between the occurrence of clopidogrel resistance and the activation of an inflammatory process. The monozygous variant of the receptor P2Y12 CT18T gene was insignificantly more frequently encountered in the unresponsive patients.
Conclusion. The laboratory phenomenon of clopidogrel resistance exists. Large multicenter studies of this issue are needed to identify simple and least expensive resistance methods and clear diagnostic criteria that enable the findings to be compared.

About the authors

N S Frolova

A. L. Myasnikov Institute of Clinical Cardiology, Russian Cardiology Research-and-Production Complex, Russian Agency for Medical Technologies

Email: frolik78@mail.ru
A. L. Myasnikov Institute of Clinical Cardiology, Russian Cardiology Research-and-Production Complex, Russian Agency for Medical Technologies

R M Shakhnovich

A. L. Myasnikov Institute of Clinical Cardiology, Russian Cardiology Research-and-Production Complex, Russian Agency for Medical Technologies

Email: shakhnovich@mail.ru
A. L. Myasnikov Institute of Clinical Cardiology, Russian Cardiology Research-and-Production Complex, Russian Agency for Medical Technologies

O V Sirotkina

B.P. Konstantinov Saint Petersburg Institute of Nuclear Physics, Russian Academy of Sciences

Email: olga_stirotkina@mail.ru
B.P. Konstantinov Saint Petersburg Institute of Nuclear Physics, Russian Academy of Sciences

A B Dobrovolsky

A. L. Myasnikov Institute of Clinical Cardiology, Russian Cardiology Research-and-Production Complex, Russian Agency for Medical Technologies

Email: abdobrovolsky@inbox.ru
A. L. Myasnikov Institute of Clinical Cardiology, Russian Cardiology Research-and-Production Complex, Russian Agency for Medical Technologies

M Ya Ruda

A. L. Myasnikov Institute of Clinical Cardiology, Russian Cardiology Research-and-Production Complex, Russian Agency for Medical Technologies

Email: ruda@cardio.ru
A. L. Myasnikov Institute of Clinical Cardiology, Russian Cardiology Research-and-Production Complex, Russian Agency for Medical Technologies

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