The ABCB1, CYP2C19, CYP3A5 and CYP4F2 genetic polymorphisms and platelet reactivity in the early phases of acute coronary syndromes
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01.09.2018 |
Mirzaev K.
Rytkin E.
Ryzhikova K.
Grishina E.
Sozaeva Z.
Fedorinov D.
Konova O.
Giliarov M.
Belyakova G.
Andreev D.
Sychev D.
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Drug Metabolism and Personalized Therapy |
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Ссылка
© 2018 2018 Walter de Gruyter GmbH, Berlin/Boston. The aim was to study seven polymorphic markers of genes encoding proteins involved in the absorption, metabolism and pharmacokinetics of clopidogrel among patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Eighty-one ACS and PCI patients older than 18 years and treated with dual antiplatelet therapy were enrolled in the study. Platelet function testing and ABCB1, CYP2C19, CYP3A5 and CYP4F2 genotyping were performed. The predictive role of categorical variables, such as genotypes (carriers and non-carriers of polymorphism), on platelet reactivity (platelet reactivity units [PRU] platelet inhibition [PI]) was assessed by logistic regression (for categorical outcomes) and linear regression (for continuous outcomes) analysis. A p-value<0.05 was considered significant. The allele frequencies were estimated by gene counting, and Hardy-Weinberg equilibrium was tested using the chi-square test. Regarding clopidogrel response, 62 patients (76.5%) were clopidogrel responders and 19 were non-responders (23.5%). Mean PRU value and the percentage of platelet inhibition were 170.0±50.9 PRU and 28.6±19.9%, respectively. The effects of the CYP2C19∗2 polymorphisms on PRU (166.0±50.8 vs. 190.7±48.2, p<0.038) and PI (30.6±20.0 vs. 18.1±16.3, p<0.013) were observed, and the rates of high platelet reactivity (HPR) were lower in CYP2C19∗1/∗1 than those in CYP2C19∗1/∗2+CYP2C19∗2/∗2 (16.2% vs. 53.8% p<0.0067). In comparison, no significant difference in PRU value and PI was observed at <5 days between the rest of polymorphisms (p>0.05). Based on the logistic regression analysis, CYP2C19∗2 (OR: 4.365, CI: 1.25-17.67, p=0.022) was an independent predictor of HPR at <5 days, as was the stent diameter (OR: 0.219, CI: 0.002-0.229, p=0.049). The remaining polymorphisms had no influence. The reactivity of the on-clopidogrel platelet in the early phase of ACS is influenced primarily by the CYP2C19 polymorphisms. We believe that the findings of the present study could supply additional evidence regarding the clinical appropriateness of the CYP2C19 genetic testing for designing suitable antiplatelet therapy in the early phase of ACS.
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Optimization of invasive treatment strategy in patients with non-ST elevation acute coronary syndrome
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01.01.2018 |
Prilutskaya Y.
Dvoretsky L.
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Kardiologiya |
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© 2019 All rights reserved. Objective: to compare strategies of invasive treatment of patients with non-ST elevation acute coronary syndrome (NSTEACS) hospitalized in 2014 and 2015. Materials and methods. We have analyzed treatment strategy used in patients with NSTEACS hospitalized in cardio-reanimation department of a city hospital during one month in two successive years (January 2014 and November 2015). We have compared indications to, and timing of coronary angiography, numbers of performed percutaneous coronary interventions (PCI) and coronary artery bypass grafting surgeries. Results. Portion of patients subjected to invasive procedures in 2014 was 26 %, in 2015-42 %. All 32 primary procedures were PCIs. An increase was due to delayed interventions (24-72 hours), which were not performed in 2014. We also more often used selective multivessel coronary stenting, what facilitated availability of invasive treatment for elderly patients. Hospital mortality of patients with NSTEACS decreased from 16 to 7 %.
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Антитромботическая терапия у пожилого полиморбидного пациента после кровотечения: вызов нашего времени
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01.01.2018 |
Atabegashvili M.
Gilarov M.
Konstantinova E.
Kostina A.
Nesterov A.
Paharkova T.
Udovichenko A.
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Rational Pharmacotherapy in Cardiology |
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© 2018 Stolichnaya Izdatelskaya Kompaniya. В последние годы наблюдается очевидная тенденция увеличения в популяции числа пожилых больных. Эти пациенты в большинстве случаев страдают несколькими коморбидными заболеваниями, что значительно утяжеляет прогноз и усложняет тактику ведения. Представлен клинический случай пожилой пациентки, длительное время страдающей сахарным диабетом 2 типа, получающей инсулинотерапию, нахо- дящейся на программном гемодиализе из-за терминальной хронической почечной недостаточности, а также имеющей постоянную форму фибрилляции предсердий. Пациентка была госпитализирована в ГКБ №1 им Н.И. Пирогова по поводу острого повторного инфаркта миокарда. Проведено экстренное чрескожное коронарное вмешательство, стентирование инфаркт-зависимой артерии стентом с лекарст- венным покрытием. Послеоперационный период осложнился развитием острой кровопотери на фоне кровотечения из верхних отделов желудочно-кишечного тракта, тяжелой анемии сочетанного генеза (постгеморрагической, нефрогенной), что потребовало от врачей принятия нестандартных решений по выбору антитромботической терапии. Данный клинический случай иллюстрирует сложности ведения пожилых полиморбидных пациентов в реальной клинической практике, и спорные вопросы, возникающие при назначении им антитромботической терапии, особенно, после развившегося кровотечения. Рекомендательные документы не могут дать ответ на все вопросы, которые ставит перед врачом повседневная практика. В каждом конкретном случае возобновление антитромботической терапии и ее оптимальный выбор для пожилого полиморбидного пациента с развившимся кровотечением является предметом дискуссии, и представляет для лечащего врача настоящий вызов.
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What are the opportunities of prasugrel in the treatment of patients with acute coronary syndrome?
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01.01.2018 |
Gilyarov M.
Konstantinova E.
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Rational Pharmacotherapy in Cardiology |
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© 2018, Stolichnaya Izdatelskaya Kompaniya. The aim of the review is presenting the possibilities and perspectives of the third generation of thienopyridine P2Y12 receptor inhibitor prasugrel in the treatment of patients with acute coronary syndrome (ACS). The main pathogenetic stage of ACS is intracoronary thrombosis, which develops on the surface of a damaged atherosclerotic plaque. The use of acetylsalicylic acid with addition of the second antiplatelet agent, so-called dual antiplatelet therapy, is a standard component in the treatment of any type of ACS, regardless of reperfusion and the selected treatment strategy. Due to some limitations in the use of clopidogrel as the second component of dual antiplatelet therapy, the possibility of prasugrel or ticagrelor usage should be considered in patients with ACS with percutaneous coronary intervention (PCI). Prasugrel therapy is associated with better clinical outcomes as compared with clopidogrel therapy in moderate or high-risk patients who undergo PCI. Because of higher bleeding risk and the lack of clinical benefits in special subgroups of patients, prasugrel must not be used in patients with a stroke or transient ischemic attack in the past. If, after a thorough individual benefit-risk assessment a decision is in favor of prescribing prasugrel to the patient older than 75 years or with a small body weight the maintenance dose of prasugrel is to be reduced by half. Real clinical practice data has shown that with following these recommendations prasugrel demonstrates optimal efficacy, safety, and even more significant impact on the prognosis than this in clinical trials. Prasugrel is able to reduce significantly the incidence of cardiovascular events such as cardiovascular death, myocardial infarction and stroke in patients with ACS who undergo PCI.
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