Репозиторий Университета

© 2019, Springer Nature B.V. The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A4*22 and CYP3A5*3) on the efficacy clopidogrel in patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Platelet activity was determined on a VerifyNow P2Y12 test system in 81 patients with ACS aged 37–91 who had PCI. The activity of CYP3A4/5 was expressed as the ratio of the concentrations of cortisol and 6β-hydroxycortisol was performed by using high performance liquid chromatography. Genotyping was performed by using real-time polymerase real-time chain reaction. The frequencies for the CYP3A5 gene, rs 776746, were identified as follows: 77 (95.1%)—CC, 4 (4.9%)—CT; the allele frequencies by loci for the CYP3A4, rs rs35599367, were as follows: 78 (96.3%)—GG, 3 (3.7%)—AG. There was no statistically significant genotype-dependent difference between the presence of a minor T and G alleles and the presence of clopidogrel resistance (OR 3.53; 95% CI 0.46–26.94; p = 0.233 and p = 0.443, respectively). The average level of the metabolic relationship (6β-hydroxycortisol/cortisol) between the clopidogrel-resistant group and the normal platelet reactivity group was not statistically significantly different: 3.3 ± 2.8 versus 3.2 ± 3.2; p = 0.947. So, the activity of CYP3A4/5 was not related to platelet aggregation rates in this model. Genotyping and phenotyping CYP3A4\CYP3A5 does not predict the antiplatelet effect of clopidogrel. More extensive research is required to establish their clinical relevance.

© 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.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Echocardiographic parameters were assessed in patients with non-ST segment elevation acute coronary syndrome, who underwent emergency percutaneous coronary intervention followed by various outpatient physical cardiac rehabilitation programs. The patients underwent physical rehabilitation for 3 months under conditions of diagnostic centre in the rehabilitation unit according to the standard program including in treadmill or bicycle exercise in the exercise therapy room or with Nordic walking in the main training block. After rehabilitation course, the left ventricular mass index significantly decreased and systolic volume and left ventricular ejection fraction significantly increased in both groups. Nordic walking training for 3 months non-ST segment elevation acute coronary syndrome induced similar positive shifts in the parameters of intracardiac hemodynamics, as standard treadmill or bicycle training program, which allows considering it as an alternative cardiac rehabilitation method.

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. In the clinical practice a physician quite often is at a loss due to “freedom of choice” granted by availability of direct oral anticoagulants (DOAC). If a patient with nonvalvular atrial fibrillation (AF) has indications for therapy with anticoagulants which DOAC should be preferred? What are benefits for a patient with ischemic heart disease and AF when definite NOAC is chosen and what are risks inherent of this choice? Answers to such questions are given in this paper.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Mainly, intracoronary thrombosis is the cause of acute coronary syndrome. The structure of the atherosclerotic plaque plays an important role in the development of the mechanism of intracoronary thrombosis. Currently, there are various radiological methods for diagnosis of atherosclerotic plaques of the coronary arteries. The current review reveals the theme of "indirect" signs of instability of atherosclerotic plaques, their combinations and occurrence, detected by computed tomography. Retrospective studies have shown the feasibility of these signs of plaques in the assessment of the prognosis of acute coronary events. The review compares the results of computed tomography (CT) and intravascular ultrasound, which is the gold standard in the diagnosis of atherosclerotic plaque morphology.

© 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 %.

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. Until today, there are no universally accepted methods for detection of unstable atherosclerotic plaques, even though many recent studies were devoted to this issue. In this article we present modern possibilities of computed tomography in visualization of atherosclerotic coronary lesion, including the detection of unstable lesions, whot in turn, can help in diagnosing subclinical exacerbation of ischemic heart disease and in the stratification of risks of acute coronary events.

© 2018 Stolichnaya Izdatelskaya Kompaniya. All rights reserved. The key to successful treatment in patients with acute coronary syndrome is maximally early revascularization of the coronary arteries. Treatment of multifocal atherosclerosis with lesions of the coronary and peripheral arteries requires coordinated work of the multidisciplinary team of doctors. Critical ischemia of the lower limbs requires urgent revascularization in order to prevent limb amputation. However, it is not always possible to perform revascularization using specialists of the same profile – endovascular or surgical. The use of hybrid methods of treatment (surgical and endovascular) allows to significantly improve the prognosis in saving the limb. The article presents a clinical observation of successful multistep treatment of a patient with acute coronary syndrome in combination with critical ischemia of the lower limb. The first stage was performed by multiple stenting of the coronary arteries with bioabsorptive scaffolds; the second stage was the hybrid treatment – femoral-tibial bypass with simultaneous recanalization and angioplasty of the lower leg arteries with good postoperative and long-term outcome.

© 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.

© 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.

© Rational Pharmacotherapy in Cardiology 2018. Background. Carriership of CYP4F2*3 (rs2108622, Val433Met) allelic variant can affect antiplatelet effect of clopidogrel, thus changing efficacy and safety of its standard dose. Aim. To study the impact of carriership of at least one CYP4F2*3 allele on the risk of resistance to clopidogrel in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Material and methods. The study enrolled 81 patients with ACS and PCI: 64 males and 17 females, mean age 63.9±10.9 years. CYP4F2 allelic variants were detected by the method of real-time polymerase chain reaction. Platelet functional activity was evaluated by a portative aggregometer - the VerifyNow P2Y12 assay. Results. Pharmacogenetic testing showed that 40 (49.4%) of ACS patients had normal genotype (CC), 38 (46.9%) patients were carriers of one associated with reduced drug metabolism allele (CT genotype), and 3 (3.7%) patients were homozygotes for T (TT genotype). Genotype and allele distribution was in the Hardy-Weinberg equilibrium (χ2=2.79; p=0.095). There were no statistically significant differences in CYP4F2*3 allele frequency between patients that are resistant to clopidogrel (PRU > 208) and in patients with a normal response to clopidogrel (PRU < 208): 36.8% vs 54.8% (p=0.17). Average platelet reactivity units (PRU) and average platelet inhibition (%) in patients with and without T allelic variant of CYP4F2 also were not significantly different: 165.34±51.03 PRU vs 174.8±51.06 PRU (p=0.407), respectively, and 29.51±21.59% vs 27.72±18.35%, respectively (p=0.69). Conclusion. Carriership of CYP4F2*3 allelic variant does not affect antiplatelet effect of clopidogrel in ACS patients. Further research on larger samples is needed to determine the role of CYP4F2 polymorphisms in personalization of clopidogrel antiplatelet therapy.

© 2018 Media Sphera Publishing Group.All rights reserved. Purpose: To assess the prevalence of atrial fibrillation (AF) and use of antithrombotic agents in adult patients with acute coronary syndrome (ACS). Materials and Methods. We consecutively enrolled all ACS patients (n=1155) who were hospitalized in two Moscowbased percutaneous coronary intervention centers (each center performs over 500 PCIs a year) between October 2017 and February 2018. AF was diagnosed in 204 patients (17.7%). The risk of thromboembolic complications was assessed using the CHA2DS2-VASc Score. The risk of hemorrhagic complications was assessed using the HAS-BLED Score. The data were processed using StatSoft Statistica 10.0 and IBM SPSS Statistics v.23 software. Results. The prevalence of diagnosed AF was 13.6%, while the prevalence of undiagnosed AF was 4.1%. Of the 179 discharged patients with AF, only 2 had a low risk of ischemic stroke (IS). One hundred and fifty patients (83.8%) eligible for oral anticoagulant therapy received oral anticoagulants. Patients with diagnosed AF were administered oral anticoagulants (OACs) significantly more often than patients with undiagnosed AF [125 (91.9%) vs. 25 (58.1%), р 0.001]. Novel oral anticoagulants (NOACs) were administered four times more often than vitamin K antagonists [120 (80.0%) vs. 29 (19.3%), р0.001]. Rivaroxaban was used in 51.3% of cases. Of the 29 patients treated with warfarin, only 3 (10.3%) achieved the target international normalized ratio (INR) at discharge. Of the 107 patients who underwent percutaneous coronary intervention (PCI), 77 patients (80%) received an OAC and two antiplatelet agents (with 74% receiving this three-agent therapy for one month), 11 patients (10.3%) received an OAC and an antiplatelet agent, and 18 patients (16.8%) received two antiplatelet agents. The only antiplatelet agent used as part of the three-agent therapy was clopidogrel. The three-agent therapy without PCI was administered in 43.1% of cases. Conclusion. We found that the prevalence of AF in patients with ACS was high. The fact that doctors administered NOACs suggests that they are aware of the need to use these agents to prevent thromboembolic complications in AF patients.

© 2018 Media Sphera Publishing Group. All rights reserved. Purpose: to analyze possible associations of clinical and genetic factors with development of ischemic stroke after exacerbation of ischemic heart disease (IHD). Materials and methods: The Russian multicenter study aimed at assessment of risk of unfavorable outcomes after exacerbation of IHD "Exacerbation of IHD: logical probabilistic ways to course prognostication for optimization of treatment" (meaning of Cyrillic acronym-oracle) was conducted in 16 centers of 7 cities in Russia. We included into the study 1 208 patients with unstable angina and ST-elevation or non-ST-elevation myocardial infarction (MI). Data on outcomes were known for 1 193 patients, 15 patients were lost for follow-up. Results. Mean duration of follow-up was 64414.45 (4-1 995) days. Shortest, longest, and mean time before development of stroke was 22, 1433 and 38956.6 days after inclusion. Patients with strokes were older, more often had history of IHD prior to index hospitalization, arterial blood pressure level compatible with stage 3 arterial hypertension, less often were smokers, and more often had MI recurrences or repetitive episodes of severe ischemia during the index hospitalization. Patients also more often had documented atrial fibrillation during hospitalization, and lower level of glomerular filtration rate. Of studied genetic markers carriage of A allele of polymorphic marker G (-1082) A of interleukin-10 gene was significantly associated with risk of stroke development. Using linear regression analysis, we constructed a model of estimation of the stroke development risk. Comparison of diagnostic value of different scales for stroke risk assessment showed that area under the curve was 0.656, 0.686, and 0.756 for the GRACE, CHA2DS2-VASc, and ORACLE scores, respectively.