ObjectiveWe evaluated atrial fibrillation (AF) patients’ perceptions of anticoagulation treatment with dabigatran or a vitamin K antagonist (VKA) for stroke prevention, according to accepted indications.MethodsThe RE-SONANCE observational, prospective, multicentre, international study used the validated Perception on Anticoagulant Treatment Questionnaire (PACT-Q) to assess patients with AF already taking a VKA who were switched to dabigatran (cohort A), and newly diagnosed patients initiated on either dabigatran or a VKA (cohort B). Visit 1 (V1) was at baseline, and visit 2 (V2) and visit 3 (V3) were at 30–45 and 150–210 days after baseline, respectively. Primary outcomes were treatment satisfaction and convenience in cohort A at V2 and V3 versus baseline, and in cohort B for dabigatran and a VKA at V2 and V3.ResultsThe main analysis set comprised 4100 patients in cohort A and 5365 in cohort B (dabigatran: 3179; VKA: 2186). In cohort A, PACT-Q2 improved significantly (p<0.001 for all) for treatment convenience (mean change V1 vs V2=20.72; SD=21.50; V1 vs V3=24.54; SD=22.85) and treatment satisfaction (mean change V1 vs V2=17.60; SD=18.76; V1 vs V3=21.04; SD=20.24). In cohort B, mean PACT-Q2 scores at V2 and V3 were significantly higher (p<0.001 for all) for dabigatran versus a VKA for treatment convenience (V2=18.38; SE =0.51; V3=23.34; SE=0.51) and satisfaction (V2=15.88; SE=0.39; V3=19.01; SE=0.41).ConclusionsSwitching to dabigatran from long-term VKA therapy or newly initiated dabigatran is associated with improved patient treatment convenience and satisfaction compared with VKA therapy.

Our findings contradicted the primary hypothesis. Apnoea up to 5 min does not lead to notable cerebral hypoxia or a decrease of brain performance in either breath-hold divers or non-divers. It seems to be the result of the compensatory mechanisms similar to the diving response aimed at centralising blood circulation and reducing peripheral O2 uptake. Adaptive changes during apnoea are much more prominent in trained breath-hold divers.

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Aim. To study the structure and incidence of the in-hospital anticoagulants prescription in patients at high risk of thromboembolic events (TEE) and to evaluate clinical characteristics of anticoagulated patients (by the example of the University Clinical Hospital (UCH) №1 of I.M. Sechenov First Moscow State Medical University (FMSMU). Material and methods. The cross-sectional retrospective study held in UCH №1 of the FMSMU, enrolled 677 patients with atrial fibrillation (AF) for whom the prevention of TEE was indicated. Results. Of 677 analyzed cases (women 70%, men 30%) only 61% of the patients received appropriate anticoagulant therapy. Warfarin was prescribed in 73% of the cases, of them unsatisfactory international normalized ratio (INR) control (time in therapeutic range less than 60%) was revealed in 79%. 8.45% of the vitamin K antagonist treated patients developed hemorrhagic complications. 16% of the patients received novel oral anticoagulants (dabigatran -14%, rivaroxaban -2%). Bleeding was fixed in 4.2% of the dabigatran treated patients and in 14.3% -in case of rivaroxaban therapy. Conclusion. More than a third of non-valvular AF patients receive inadequate antithrombotic therapy in routine clinical practice. 75% of the anticoagulated patients are prescribed the vitamin K antagonists (typically warfarin) as a traditional anticoagulant. At that, only in 21.7% of the patients receiving vitamin K antagonists, this therapy may be considered adequate. Low incidence rate of the novel oral anticoagulants prescription despite the advantages of such treatment also calls attention. Цель. Изучить структуру и частоту назначений антикоагулянтов в стационаре (на примере Университетской клинической больницы (УКБ) №1 Первого московского государствен-ного медицинского университета (МГМУ) им И.М. Сеченова) среди пациентов с высоким риском развития тромбоэмболических осложнений (ТЭО), а также клинические харак-теристики пациентов, получающих антикоагулянтную терапию. Материал и методы. Одномоментное поперечное ретроспективное исследование, проведенное в УКБ №1 Первого МГМУ им И.М. Сеченова, включило 677 пациентов с фиб-рилляцией предсердий (ФП), которым показана профилактика ТЭО. Результаты. Из 677 проанализированных пациентов (70% женщин, 30% мужчин) лишь 61% получают показанную им антикоагулянтную терапию. На долю варфарина пришлось 73%. Среди пациентов, получающих варфарин, в 79% случаев выявлен неудовлетворительный контроль международного нормализованного отношениям (МНО) вследствие пре-бывания вне терапевтического окна менее 60% времени. У 8,45% пациентов, получавших антагонисты витамина К, развились геморрагические осложнения. Новые перораль-ные антикоагулянты получали 16% пациентов (14% -дабигатран, 2% -ривароксабан). На долю пациентов, получавших дабигатран, пришлось 4,2% кровотечений (от числа получавших данный препарат), на ривароксабан -14,3%. Заключение. Более трети пациентов с ФП неклапанной этиологии в рутинной клинической практике получают неадекватную антитромботическую терапию. Примерно в 75% слу-чаев ...

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Aim. To study the clinical outcomes (achievement of target blood pressure [BP]) and tolerability of antihypertensive and hypolipidemic therapy with fixed combinations of indapamide/perindopril, amlodipine/perindopril, amlodipine/indapamide/perindopril and rosuvastatin in patients with hypertension and high/very high cardiovascular risk in real clinical practice.Material and methods. The study included 16,788 patients from 104 cities of the Russian Federation. The duration of observation was 12 weeks. All patients had three monitoring visits. BP level was measured twice during the visits: the arithmetic mean of the obtained parameters was calculated. The results of the study were analyzed and presented by descriptive statistics.Results. The average age of the patients was 60.6±10.2 years; 42.2% of the patients were men and 57.8% women. Patients who demonstrated systolicdiastolic hypertension (BP>140/90 mm Hg) at the initial visit accounted for 73.9% (n=12,413) of the total number of participants. The average level of systolic BP at the inclusion into the study was 162.94±13.07 mm Hg, the level of diastolic BP was 93.43±8.61 mm Hg. As expected, the Russian population consists of over 90% of patients with very high (57%; n=9,586) and high (35.9%; n=6,022) additional cardiovascular risk. Despite the fact that the overwhelming majority of patients with hypertension had a high and very high additional risk, more than a third of patients received monotherapy to control their BP level (36.8%; n=6,182), while 13.8% of patients (n=2,321) had never received antihypertensive therapy before. According to the results of therapy with combination drugs based on perindopril, 92.7% of patients managed to reach the target BP levels of <140/90 mm Hg. After treatment the average level of systolic BP decreased from 162.94±13.07 mm Hg to 127.80±7.56 mm Hg, and the level of diastolic BP – from 93.43±8.61 mm Hg to 78.54±5.59. Adherence to the treatment in more than 97% of cases was recognized as very high and high. Only 10 adverse events were recorded on a large sample of patients during 12 weeks of treatment.Conclusion. In the Russian population, 73.9% of patients with hypertension and high/very high risk do not achieve the target BP levels. Application of combined therapy based on fixed combinations with perindopril allows achieving effective BP control in 93% of patients with hypertension having high and very high risk during 12 weeks with good tolerability of treatment.

Aim. To search for new pharmacogenetic biomarkers of bleeding risk in patients taking rivaroxaban and dabigatran for different indications: atrial fibrillation, endoprosthesis of large joints of lower limbs.Material and methods. The study enrolled 29 patients (17 patients received dabigatran and 12 –rivaroxaban), who had hemorrhagic complications during taking direct oral anticoagulants. To find new pharmacogenetic biomarkers of bleeding risk, a next generation sequencing (NGS) was performed for selected candidate genes.Results. Among the patients with bleeding who received dabigatran, 13 variants of the nucleotide sequence showed statistically significant deviation from the population values: 11 in the CES1 gene and 2 in the ABCB1 gene. Among the patients with bleeding who received rivaroxaban, 7 variants of nucleotide sequence showed significant deviation: 4 in the ABCG2 gene, 2 in the CYP3A4 gene, and 1 in the ABCB1 gene.Conclusion. The identified in this study polymorphisms of candidate genes ABCB1, ABCG2, CES1, CYP3A4 were associated with the risk of bleeding in patients taking rivaroxaban and dabigatran. It makes an important contribution to the pharmacogenetics of direct oral anticoagulants and require additional assessment of clinical significance in further studies.

ФАРМАКОГЕНЕТИКАВозможность владеть генетической информацией позволила начать внедрение персонализированной медицины в клиническую практику. Генетические иссле-дования начали показывать, что некоторые лекарства в определенных условиях очень эффективны для одних пациентов и неэффективны, а иногда даже опасны -для других. Поэтому на стыке фармакологии и генетики воз-никла фармакогенетика -наука, изучающая роль генети-ческих факторов в формировании фармакологического ответа организма человека на лекарственное средство [1]. Это может дать возможность врачу персонализиро-ванно выбрать как само лекарство, так и дозу у конкрет-ного больного и обеспечить максимальную эффектив-ность и безопасность препарата.Роль наследственности в формировании индивиду-ального ответа на лекарственные средства была известна давно, понимание механизмов влияния гене-тических факторов на эффективность и безопасность фармакотерапии стало возможным лишь с развитием методов молекулярной биологии и реализацией меж-дународной программы «Геном человека». Последние данные, имеющиеся о строении генома человека, явно показывают, что существует множество вариаций генов, которые объясняют различия в абсорбции пре-парата, распределении, метаболизме, выведении и в итоге ответную реакцию организма на фармацевтиче-ский препарат. Такие предварительные успехи дали понять, что подобное исследование позволит получить такую медицину, которая окажется и индивидуальной, и точной. Personalized medicine appeared about three decades ago. Even then many scientists, researchers, doctors were interested into it. However, only after the full opening of the human genome in 2001, personalized medicine could to give the opportunity for some pathologies (oncology, rheumatology, cardiology) to choose the most effective treatment with minimal adverse drug reactions for a specific patient. The opportunity to own genetic information gives the chance to suspect, to predict, to expect the onset of the disease. Personalized medicine is able in some cases to say exactly whether the drug can work for the patient, moving us to «treat not a disease, but the patient.» But doctors to this day when determining risk factors focus on individual characteristics of the patient, such as age, gender, body weight, co-morbidities, and based on that prescribe medications, correct dose and in case of ineffectiveness change the treatment regimen. Apparently they don't believe in personalized medicine, afraid of it and I don't want to associate with it, because as many think on the basis of their experience and knowledge they can decide which drug and what dose to prescribe. Also, there are a number of reasons related to privacy, security, problem of training, which will soon need to be addressed.