Terapevticheskii arkhivTerapevticheskii arkhivТерапевтический архив0040-36602309-5342LLC Obyedinennaya Redaktsiya30610Editorial articleПередовая статьяClopidogrel resistance in patients with acute coronary syndromeРезистентность к клопидогрелу у больных с острым коронарным синдромомFrolovaN SФроловаНаталья Сергеевна

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

врач, палата интенсивной терапии, отд. неотложной кардиологии; Институт клинической кардиологии ФГУ РКНПК Росмедтехнологий

frolik78@mail.ruShakhnovichR MШахновичРоман Михайлович

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

канд. мед. наук, ст. науч. сотр, отд. неотложной кардиологии; Институт клинической кардиологии ФГУ РКНПК Росмедтехнологий

shakhnovich@mail.ruSirotkinaO VСироткинаОльга Васильевна

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

канд. биол. наук, ст. науч. сотр., лаб. молекулярной генетики человека РАН; Петербургский институт ядерной физики им. Б. П. Константинова РАН

olga_stirotkina@mail.ruDobrovolskyA BДобровольскийАнатолий Борисович

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

д-р биол. наук, проф., вед. науч. сотр. лаб. клинических проблем атеротромбоза; Институт клинической кардиологии ФГУ РКНПК Росмедтехнологий

abdobrovolsky@inbox.ruRudaM YaРудаМихаил Яковлевич

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

д-р мед. наук, проф. рук. отд. неотложной кардиологии; Институт клинической кардиологии ФГУ РКНПК Росмедтехнологий

ruda@cardio.ruA. L. Myasnikov Institute of Clinical Cardiology, Russian Cardiology Research-and-Production Complex, Russian Agency for Medical TechnologiesИнститут клинической кардиологии ФГУ РКНПК РосмедтехнологийB.P. Konstantinov Saint Petersburg Institute of Nuclear Physics, Russian Academy of SciencesПетербургский институт ядерной физики им. Б. П. Константинова РАН15082010828NO8 (2010)ТОМ 82, №8 (2010)142009042020Copyright ©; 2010, Consilium MedicumCopyright ©; 2010, ООО "Консилиум Медикум"2010Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://ter-arkhiv.ru/0040-3660/article/view/30610

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.

Цель исследования. Выявление частоты развития резистентности к клопидогрелу у больных с острым коронарным синдромом (ОКС) и ее влияния на прогноз у таких больных. Материалы и методы. Наблюдали 75 больных с ОКС, получавших клопидогрел. Проводилась оптическая агрегатометрия с АДФ 20 мкмоль. Критерии резистентности: агрегация тромбоцитов исходно, агрегация тромбоцитов на 7-й день, % < 10%. Определяли маркеры воспаления (ИЛ-6, ИЛ-10 и С-РБ). Исследовали генетические полиморфизмы: гена субъединицы IIIa - Leu33Pro, гена рецептора Р2Y12: С18Т и G36Т и гена СYР3*А4 (А-293G). Результаты. Согласно принятому критерию резистентности, 54 (72%) больных были чувствительными, а 21 (28%) - резистентными к клопидогрелу. Среди больных с подъемом сегмента SТ на электрокардиограмме резистентность выявлена у 7 (23%), а среди больных без подъема сегмента SТ - у 14 (31%). Резистентные больные достоверно чаще получали при поступлении в клинику нагрузочную дозу клопидогрела 300 мг, тогда как чувствительные - 600 мг. Исходно у резистентных больных оказался достоверно более низкий уровень АТ в отличие от чувствительных больных, который повышался к 7-му дню. Влияния на прогноз резистентность к клопидогрелу, определенная по данному критерию, не оказала. При разделении больных по показателям агрегации на квартили неблагоприятные проявления недостоверно чаще происходили в 3-м и 4-м квартилях. Не выявлено четкой зависимости между возникновением резистентности к клопидогрелу и активацией воспалительного процесса. У резистентных больных недостоверно чаще встречался монозиготный вариант гена С18Т рецептора Р2Y12. Заключение: феномен лабораторной резистентности к клопидогрелу существует. Требуются крупные многоцентровые исследования по данному вопросу для выявления простых и наименее затратных методов резистентности, а также четких диагностических критериев, позволяющих сравнивать получаемые данные.

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