Background Despite the well-studied safety profile of dabigatran, its interactions with genetic polymorphism parameters are poorly understood, especially in patients with moderate chronic kidney disease (CKD). The study assessed whether genetic factors can contribute to CKD and alter dabigatran concentration. Methods Patients with atrial fibrillation (AF) and stage 3 CKD treated with dabigatran 110 or 150 mg have been included in the study. Real-time polymerase chain reaction was used to evaluate single-nucleotide polymorphisms of the ABCB1 gene (rs1045642 and rs4148738) and CES1 gene (rs2244613). A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index. Results A total of 96 patients aged 51–89 years (median age: 75 years) were evaluated. Patients on a reduced regimen of 110 mg twice a day were older (79.8 vs. 67.9, p < 0.0001) and had lower creatinine clearance (49.7 vs. 62.3 mL/min/1.73 m2, p = 0.015). Patients with the rs2244613 CC genotype had lower C/D values (70% reduction in the mean C/D vs. AA genotype, p = 0.001). Linear stepwise regression has shown the CKD epidemiology collaboration to be the only significant predictor of C/D among genetic factors and kidney function characteristics. During the median follow-up of 15 months, there were 15 bleedings in 13 patients. Conclusions Polymorphism of CES1 rs2244613 can contribute to the safety of dabigatran in patients with AF and CKD. There was no influence of the aforementioned polymorphisms of ABCB1 on dabigatran trough plasma concentrations and C/D. Kidney function is a mainstay of clinical decision-making on direct oral anticoagulant (DOAC) dose, and further knowledge should be accumulated on the role of genetic factors.

Реальная клиническая практика применения антикоагулянтных препаратов в настоящее время является одним из самых актуальных направлений в кардиологии. Обновленные рекомендации 2016 г. по ведению пациентов с фибрилляцией предсердий (ФП) [1] не дают ответа на вопрос о том, какому из прямых пероральных анти-коагулянтов (ППОАК) отдавать предпочтение в определенных клинических ситуациях, что заставляет практикующих врачей обращаться к результатам как рандомизированных клинических исследований (РКИ), так и к немногочисленным данным реальной клинической практики. Кроме того, ретроспективный анализ баз данных страховых компаний, статистическая обработка которых представляет некоторую трудность, и небольшие про

In recent years, both Russian and foreign authors have published many papers on anticoagulant therapy for atrial fibrillation (AF). The largest are devoted to the study of direct oral anticoagulants (DOACs), which have appeared in this field since 2009, and their comparison with vitamin K antagonists (VKAs) in terms of efficacy, safety and other important characteristics. There are far fewer studies on DOACs and their comparison with VKAs and with each other in patients with AF and reduced kidney function. Most of them are retrospective. Meanwhile, the prevalence of chronic kidney disease (CKD) in the population is very high, and doctors are faced with a problem of selecting anticoagulant therapy for these patients.Purpose. To assess the effect of VKAs and DOACs on renal function in real clinical practice in patients with AF depending on the stage of CKD.Materials and methods. A prospective single-centre non-randomized non-interventional observational study in parallel groups was conducted. The study included 92 patients with AF and CKD of 1-4 stages (S1-S4). The comparison group consisted of 35 patients with AF without concomitant CKD. The patients’ age ranged from 44 to 94 years (mean age was 72.2 ± 8.5 years). Patients of both groups received anticoagulant therapy with VKA (warfarin) or one of the registered in the Russian Federation DOACs (dabigatran, rivaroxaban, apixaban). During the observation (median was 10 months), follow-up visits were every 3 months. On visits we conducted the evaluation of effectiveness (strokes / TIA and thromboembolic complications) and safety (major and minor hemorrhagic events) of anticoagulant therapy, as well as the dynamics of kidney function (CC by Cockroft-Gault, GFR by CKD-EPI).Results. The main results are devoted to patients with AF and concomitant CKD. Significant dynamics of the kidney function depending on the anticoagulant taken (VKA or representatives of the DOACs class) were not identified. There were not any thromboembolic complications and major bleedings during the observation period. Statistically significant more minor bleedings on any dose of rivaroxaban in comparison with other anticoagulants were identified.Conclusions. In patients with AF and CKD, there was no significant effect of one or another anticoagulant on the kidney function, which is probably related to the concomitant nephroprotective therapy obtained in a large percentage of cases (ACE inhibitors / ARA, calcium antagonists, statins). Therapy with DOACs and warfarin in patients with AF and CKD for an average of 10 months of followup was effective and safe. In case of AF and CKD combination, the use of dabigatran or apixaban seems to be more preferable in relation to minor bleedings, the use of which less often leads to the development of hemorrhagic events.

Aim. Syncopal condition in young people are a relatively frequent and poorly understood medical problem. Non-cardiogenic syncope is not sufficiently studied because often they are not raise fears among doctors or patients, and at the same time their causes are associated with many complex medical and diagnostic aspects. The aim of the presented work is to identify the most significant risk factors in the development of non-cardiogenic syncopal conditions, identify triggers and assess the relationship between these factors, the lifestyle and development of syncope.Material and methods. The article presents the results of a descriptive research, including 1031 young people with a history of syncope episodes. The study took into account the presence of chronic diseases which could become a syncope trigger. External triggers (prolonged upright staying, stuffy room, and so on) were also determined.Results. In a multifactor survey of students living in Russia and abroad, the more frequent occurrence of non-cardiogenic syncopal episodes in young girls compared with young men was found. The effect of longterm upright and oxygen corporal were most likely risk factors for syncope.Conclusion. A significant correlation was found between the onset of reflex syncope and the presence of anemia and autonomic dysfunction syndrome. We proved the absence of a correlation between the level of daily load and the frequency of syncope conditions.

Цель. Оценить возможности повышения эффективности и безопасности использования антикоагулянтной терапии у пациентов с фибрилляцией пред-сердий (ФП) неклапанной этиологии в рамках функционирования кабинета контроля антикоагулянтной терапии на базе университетской клинической больницы. Материал и методы. Наблюдательное проспективное исследование (регистр), включающий 325 пациентов с неклапанной ФП, получающих раз-личную антикоагулянтную терапию для профилактики тромбоэмболических осложнений (ТЭО). Средняя продолжительность наблюдения 24±12 мес. Результаты. В настоящее время более 95% пациентов продолжают прием антикоагулянтов и наблюдение в кабинете контроля антикоагулянтной тера-пии. Всего в исследовании было зафиксировано 37 кровотечений, из которых 19 "малых" и 18 "больших". По общему числу кровотечений у пациентов, вклю-ченных в регистр, достоверных различий между варфарином и НОАК не отме-чается (p>0,05). Количество больших кровотечений у пациентов, получающих терапию варфарином достоверно больше, чем у пациентов на НОАК (p<0,05), а число малых -достоверно меньше на варфарине (p<0,05). По общему числу кровотечений антикоагулянты расположились следующим образом: дабига-тран (у 5,13% пациентов), варфарин с временем пребывания в целевом МНО 40% и более (у 10,34%), ривароксабан (у 14,3%) и апиксабан (у 26,9%). Боль-шую частоту кровотечений на апиксабане можно объяснить достоверно боль-шим средним возрастом пациентов (р<0,05), что само по себе является дополнительным фактором риска геморрагических событий. Следует отме-тить, что по частоте больших кровотечений варфарин оказался достоверно хуже, чем любой из представителей НОАК -дабигатран, ривароксабан и апиксабан. За время наблюдения тромбоэмболические осложнения были отмечены только у 3 пациентов (0,9% от общего числа получающих антикоагу-лянты). Заключение. Проведение антикоагулянтной терапии в рамках работы специ-ализированного кабинета по ее контролю достаточно эффективно и без-опасно для пациентов с неклапанной ФП. На терапии антагонистами вита-мина К (даже при неплохом контроле МНО) достоверно чаще происходят крупные (потенциально жизнеугрожающие) кровотечения, в то время как на фоне приема НОАК чаще регистрируются малые кровотечения, требующие зачастую лишь непродолжительной отмены препарата. Aim. To evaluate the possibility to increase the effectiveness and safety of anticoagulation therapy in nonvalvular atrial fibrillation (AF) under the circumstances of an office for anticoagulation control located at the University Clinics. Material and methods. Observational prospective study (registry), included 325 patients with nonvalvular AF, taking various anticoagulation drugs for the prevention of thromboembolic complications (TEC). Mean duration of follow-up is 24±12 months.Results. At the current moment about 95% of patients continue taking anticoagulants and follow-up in the office of anticoagulation control. Totally there were 37 bleedings marked, of those 19 minor and 18 major. By the general quantity of bleeding cases there is no significance in the diff...