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Objective: analysis of domestic scientific literature to identify ways of applying the Beers criteria, frequency of prescriptions and the structure of potentially inappropriate medications (PIMs) in elderly patients.Material and methods. The search for publications was carried out in Google Scholar abstract database, as wel as in eLibrary and CyberLeninka information-bearing networks for the period from 2013 to 2023. In total, 34 articles were found, among which 18 sources used Beers criteria as a tool for identifying PIMs.Results. In inpatient therapeutic departments, the maximum frequency of PIMs prescriptions according to the Beers criteria was 66.6% of cases, in surgical departments – 70%, in psychiatric departments – 90.4%, and in outpatient treatment settings – 28%. Non-steroidal anti-inflammatory drugs at different diseases were the most prescribed group of PIMs in both inpatients and outpatients. Surgical hospitals took the leading position in prescribing these drugs; specifically, more than 2/3 of elderly patients (75%) received them. According to two studies describing clinical cases of drug-induced falls in patients, the Beers criteria were effective in identifying drugs that can provoke this condition. One of papers presented application of Beers criteria to assess the economic affordability of replacing PIMs with safer new generation drugs.Conclusion. An analysis of domestic literature data has shown various ways of applying the Beers criteria, the frequency of prescriptions, and the most common PIMs. This information will help healthcare workers to be more wary of such drugs and think over applying the Beers criteria in routine practice of geriatric patients, which will further prevent or reduce the number of adverse drug reactions.

Expert Council: Drapkina O. M., Vavilova T. V., Karpov Yu. A., Kobalava Zh. D., Lomakin N. V., Martynov A. I., Roitman E. V., Sychev D. A.Scientific communities: the Russian Society for the Prevention of Non-Communicable Diseases (ROPNIZ), the Russian Scientific Medical Society of Therapists (RNMOT), the Russian Antithrombotic Forum (RAF), the National Association for Thrombosis and Hemostasis (NATH).

Aim. To compare the kinetics of dissolution (in vitro) and some pharmacodynamic and pharmacokinetic parameters of branded generic preparations of acetylsalicylic acid (ASA) in buffered form in cardioprotective doses [ASA 75 mg+Mg(OH)2 15.2 mg], which differ in the composition of excipients, with a reference drug.Material and methods. Patients with cardiovascular diseases who had indications for ASA monotherapy (n=75) were included in a one-center open postregistration comparative non-randomized study. Patients were divided into 3 groups for treatment with one of the three studied drugs: Cardiomagnyl® (comparison drug; group 1; n=25), Trombital® (group 2; n=25) and Fazostabil® (group 3; n=25). A study of the kinetics of dissolution of the studied drugs in vitro under conditions of pH 1.2 has been performed. Also, platelet aggregation in response to arachidonic acid, the concentration of salicylic acid and the level of serum thromboxane B2 were studied in the compared groups.Results. The average release profile of ASA by the 30th minute from Cardiomagnyl® was higher than for Trombital® and Fazostabil® (95.7%, 84.8%, 76.5% respectively). The similarity factor (f2) of ASA release for Trombital® was 39.3, and for Fazostabil® - 34.2. An index of f2

Arterial thrombosis is a result of complex interaction between blood cells, soluble coagulation factors in plasma and vessel wall. Antiplatelet drugs do not always provide the necessary antithrombotic effect of sufficient strength, because their influence does not extend to all three factors involved in this process. Low doses of direct oral inhibitors of thrombin are able to potentiate antithrombotic effect of antiplatelet therapy. The combination of rivaroxaban in a dose of 2.5 mg and standard double antiplatelet therapy turned out to be the most promising for clinical use, since studies with dabigatran and apixaban at the II and III stages of the trials were found to be unsuccessful due to the unacceptably high frequency of bleeding. Studies of the combination of rivaroxaban at a dose of 2.5 mg and standard antiplatelet therapy conducted in previous years among patients with acute myocardial infarction showed a decrease in the frequency of complications of atherothrombosis associated with their ischemic nature, while at the same time there was a slight increase in hemorrhagic complications. In the COMPASS study the combination of rivaroxaban (2.5 mg) plus aspirin reduced the risk of the primary endpoint (myocardial infarction, ischemic stroke, cardiovascular death) more significantly than aspirin alone in patients with stable ischemic heart disease and ischemic brain disease. The pathophysiological rationales for the use of low doses of rivaroxaban when added to dual antiplatelet therapy are considered, and the significance of recent studies in patients with acute coronary syndrome, stable ischemic heart disease and in the prevention of ischemic stroke is discussed.

Review presents data on medicines from the new group of cardiovascular drugs, direct oral anticoagulants (DOACs) inhibitors, as antidotes for DOAC when stopping life-threatening bleeding. DOAC therapy is accorded by hemorrhages with lower frequency than therapy by indirect anticoagulants, but really exist. New antidotes for DOACs are idarucizumab, andexanet, ciraparantag. The need in antidotes for DOAC may suddenly appear in spontaneous bleeding, during surgical operation, invasive procedure, due to trauma, in patients with stroke, kidney or liver failure. Data is given on the frequency of the main types of bleeding while taking new oral anticoagulants. Information concerning use of antidotes for DOACs in bleedings as well as use of non-specific therapy are reviewed.

Dual antiplatelet therapy, including clopidogrel and aspirin, in a significant share of patients after acute coronary syndrome (ACS) is characterized by high level of platelet reactivity, which is associated with an increased incidence of cardiovascular events. Perhaps it will make reasonable the prescription of new antiplatelet drugs, particularly the combination of ticagrelor with aspirin.Aim. To assess the cost-effectiveness of VerifyNow P2Y12 platelet reactivity testing in patients after ACS.Material and methods. The analysis was performed for patients aged 55 years after ACS by modeling based on the results of the PLATO trial considering Russian epidemiological data. The time horizon of simulation was 5 years. It was assumed that the patients were receiving either generic clopidogrel or ticagrelor for 1 year, or before maintenance treatment VerifyNow P2Y12 assay had been performed, and the patients with platelet reactivity index >230 24-48 hours after ACS were receiving ticagrelor and the remaining patients - generic clopidogrel. It was expected that after 1 year the patients would discontinue treatment with clopidogrel or ticagrelor, and hereafter additional therapeutic effect of their use would be absent. The costs of antiplatelet agents in the reference case corresponded to the weighted average price of public procurement in 2013 in Russia. The costs of treatment of complications corresponded to the compulsory health insurance rates for St. Petersburg in 2014. The cost and life expectancy were discounted at 3.5% per year.Results. The platelet reactivity test and the prescription by its results of the combination of clopidogrel plus aspirin or ticagrelor plus aspirin can prevent 5 myocardial infarction and 6 deaths per 1000 patients additionally as compared with the prescription of clopidogrel plus aspirin combination to all patients. The costs for one additional year of life as compared with the combination of clopidogrel plus aspirin were 376.5 and 373.2 thousand rubles, respectively, the costs for one additional quality adjusted life year (QALY) were 433.8 and 509.8 thousand rubles, respectively. The total predictive value of costs per 1 patient with ACS using the test was 32% lower than in the routine use of ticagrelor in all patients.Conclusion. Assessment of platelets reactivity using VerifyNow P2Y12 assay in patients with ACS and modification of antithrombotic therapy in accordance with the received data can be considered as a cost-effective intervention which can reduce treatment costs as compared with the routine use of new antithrombotic drugs.

Aim. To evaluate the clinical efficacy, safety, and effects of the nonsteroidal anti-inflammatory drug lornoxicam on inflammatory markers in non-ST-segment elevation acute coronary syndrome (NSTEACS). Subjects and methods. Eighty-five patients with NSTESCS were enrolled in a prospective randomized study. They were divided into 2 groups: 1) patients received lornoxicam (8 or 12 mg/daily) for 15 days in addition to standard treatment and 2) controls. Cardiovascular outcomes and the levels of C-reactive protein (CRP), IL-6, and IL-10 were determined. Results. The lornoxicam group exhibited a significant reduction in CRP and a decrease in IL-6. There was also a significant increase in IL-10 levels in this group. A 6-month follow-up indicated a significant reduction in the number of cardiovascular events (nonfatal myocardial infarction, unstable angina, coronary death). Conclusion. Lornoxicam reduces the risk of poor cardiovascular outcomes in patients with NSTEACS and the levels of inflammatory markers.

Aim. To study morpho-functional state and pulse wave velocity (PWV) in the main arteries (MA) in older patients with arterial hypertension (AH) and chronic heart failure (CHF).Material and methods. Totally 122 patients studied (30 female) with AH+CHF at the age of 60-90 y.o., mean age 76,8±1,3. All patients had AH of the 3rd stage, 32 had isolated systolic hypertension (ISAH). AH of the 1st grade had 32, 2nd grade — 12, 3rd grade — 28 pts. CHF was at 1-2 stage with mean functional class 1,85±0,06. Control consisted of 48 healthy individuals at the age 19-25 (20,6±1,5). All participants underwent EchoCG and Dopplerography of common carotid arteries (CCA), brachial (BA) and femoral (FA) arteries with measurement of the diameter (D), intima-media thickness (CIM), velocity and volume values. Results. In patients with AH minute volume was 40% higher than in healthy individuals: by 24,4% due to inotropic and by 15,6% — chronotropic reserves. Values of CIM and D in patients and in controls did not change with posture and were higher in patients. Velocity and share kinetic energy were lower in patients than in controls. PVW in MA in patients with AH was 54-60% faster than in controls. The relation of PWV CCA: BA — 1:4,4; CCA: FA — 1:6,4-6,9; BA: FA — 1:1,5, was the same in patients and controls. There was no correlation between PWV and CIM, D and BP in young patients. Also the positive correlation is found for the time of pulse wave and heart rate.Conclusion. PWV does not directly relate to MA rigidity. Probably it is more depended on the conditions of the regulatory mechanisms of cardiovascular system and their reaction on everchanging states of central and peripheral hemodynamics, as with degeneration processes of aging, and can be named as one of the parts in adaptive correction of hemodynamics in MA. The increase of PWV and its kinetic energy compensates the loss of of blood flow velocity and maintains its volume by the unit of time during rapid phase of circulation.

Цель исследования: изучить влияние велотренировок со свободным выбором нагрузки на морфофункциональное состояние магистральных артерий больных артериальной гипертензией (АГ) пожилого возраста. Материалы и методы. Обследовано 112 больных АГ II и III стадии в возрасте от 60 до 89 лет (средний возраст 76,3±1,32 лет), из них 29 женщин. Среди исследуемых больных АГ II стадии - 8%, III - 92%. Среднее АД при поступлении в стационар: систолическое-152,6±1,87 мм.рт.ст., диастолическое-96,3±1,61 мм.рт.ст. ЧСС-75,01±1,24 уд. в мин. У 78% больных была ИБС. У всех отмечалась ХСН. Средний ФК 1,85±0,07. Обследование проводилось с использованием допплерографии общих сонных (ОСА), плечевых (ПА) и бедренных артерий (БА). Определялись: толщина интима-медия (ТИМ), диаметр артерий (ДА), скоростные показатели кровотока: Vmax, Vmin, Tamax. Во всех артериях определялась скорость пульсовой волны (СПВ). Больные рандомизированы на две группы: основная-72 больных, получавших ВТ в режиме СВН в сочетании с медикаментозной терапией; сравнения - 40. Результаты. В обеих группах при поступлении в стационар отмечалось увеличение ДА, снижение скоростных показателей кровотока. После лечения у больных основной группы отмечалась тенденция к уменьшению ТИМ в ОСА на 13%, БА на 7,6%, ПА - 5,7%. ДА на фоне лечения существенно не изменился. В основной группе V max увеличилась в ОСА на 21%, в БА-41%, ПА - 27,5%. V min в основной группе увеличилась во всех артериях: в ОСА на 34%, БА-29%, ПА - 21%. На фоне лечения в основной группе V Tamax увеличилась во всех артериях в среднем на 15-20%. После лечения в группе сравнения ТИМ и ДА существенно не изменились. Отмечалась тенденция к увеличению V max в ОСА на 9%, в ПА - 12%, в БА -25%. V min в группе сравнения на фоне лечения существенно не изменялась во всех артериях. Tamax в группе сравнения имела тенденцию к увеличению в ОСА на 10%, Ба-15%, ПА-17%. СПВ обеих групп достоверно не различалась и составила в ОСА -1,52±0,03 м/с, в ПА -5,2±0,13 м/с, в БА-8,1±0,17 м/с. После лечения в основной группе СПВ увеличилась в ОСА и БА на 16%, в ПА на 13% (р>0,05), в группе сравнения СПВ не изменилась. Заключение. На фоне лечения больных ВТ уменьшилась ТИМ во всех артериях. Включение ВТ в комплексную терапию больных АГ пожилого возраста улучшает скоростные показатели кровотока: наибольшее увеличение скорости кровотока наблюдалось в ОСА и ПА. Применение ВТ в комплексном лечении больных АГ СПВ во всех артериях существенно не изменялась.

The COVID-19 mortality is associated with an increase in interleukin-6 (IL-6) levels. Levilimab is an anti–IL-6 receptor antibody with proven clinical efficacy in patients with severe COVID-19.The aim of the study was to assess the association of COVID-19 severity and levilimab effectiveness with IL-6 levels and to explore the potential for using levilimab in other conditions accompanied by cytokine release syndrome.Materials and methods: the subgroup analysis was based on the data of COVID patients with known baseline IL-6 levels from the CORONA clinical study. Subgroups were formed according to baseline IL-6 levels: ≤5 pg/mL (normal) and >5 pg/mL (elevated). The subgroup analysis included descriptive statistics of the patients and time courses of their clinical and laboratory findings (at screening, on the day of investigational product administration, and further until day 14). In order to compare the percentages of patients who had required rescue therapy, the authors used Fisher's exact test.Results: the subgroup analysis included 91 patients (47 from the levilimab group and 44 from the placebo group). At baseline, the authors observed elevated levels of IL-6 in 31/47 (66%) subjects in the levilimab group and 29/44 (48.4%) subjects in the placebo group. The subjects with elevated IL-6 demonstrated more pronounced clinical signs of pneumonia and abnormalities in inflammatory markers. Elevated baseline IL-6 levels were associated with the need for rescue therapy (OR=3.714; 95% CI: 1.317–9.747; p=0.0183); this association was stronger in the placebo group (OR=8.889; 95% CI: 2.098–33.31; p=0.0036). Also, the placebo group showed long-term abnormalities in the clinical and laboratory findings.Conclusions: IL-6 is one of the key elements in the pathogenesis of cytokine release syndrome related to COVID-19 and other conditions. Elevated IL-6 levels are associated with the severity of COVID-19. Inhibition of IL-6 receptors by levilimab leads to clinical improvement in patients with severe COVID-19, suggesting the effectiveness of levilimab in pathogenesis-oriented therapy for cytokine release syndrome of other aetiologies.

The article presents an overview of publications describing the mechanisms of the development of the pathological process in patients infected with SARS-CoV-2 coronavirus. The authors analysed publications showing that damage to the endothelium and endothelial glycocalyx is the main factor influencing the development of coronavirus COVID-19 infection. It is the endothelium inflammation caused by a virus that leads to the dysfunction of the vascular system and the development of coagulopathy. Using scanning electron microscopy and flow cytofluorimetry, we showed that patients with COVID-19 of moderate severity (CT2) had significant desquamation of endothelial cells (concentration of circulating endothelial cells (CEC) in blood is 300-400 cells/ml whereas the normal range is no more than 10 cells/ ml). Such desquamation should cause exposure of the pro-inflammatory and thrombogenic subendothelial matrix, which, as a results, leads to the development of thrombotic disorders of the circulatory system. Therefore, it is only natural to try to counteract disease progression by protecting the endothelial glycocalyx from damage. Sulodexide, a mixture of fast-moving heparin fraction (80%) and the glycocalyx element dermatan sulfate (20%) obtained from the mucous membrane of the small intestine of pigs, is very promising in this regard. This drug can significantly reduce the inflammatory process, protect the glycocalyx and endothelium from damage, resulting in lowering the degree of thrombus formation in patients with coronavirus COVID-19 infection, which relieves the course of the disease and improves its outcome. The experimental data presented in the review, although obtained in not large enough population of patients, allow us to consider sulodexide a promising drug that protects the endothelium and suppresses thrombosis in COVID-19.

Thrombocytopenia in blood count may be a reflex of haemostatic problems of different origin – from autoimmune disease to iatrogenic nature. Sometimes, thrombocytopenia may be revealed in patient with coronary heart disease before PCI procedure as well as some hours or days later. Dual antithrombotic therapy and thrombocytopenia have the same main side effect – bleeding. Etiology of disease and details of medical decision before percutаneous coronary intervention (PCI) in CHD patients are discussed.

Use of antiplatelet therapy in the world indicates real difference in individual drug effect between patients, including the effect on prognosis. Problems of personification of individual approach, concerning antiplatelet therapy, are discussed.

Dual antiplatelet therapy, including clopidogrel and aspirin, in a significant share of patients after acute coronary syndrome (ACS) is characterized by high level of platelet reactivity, which is associated with an increased incidence of cardiovascular events. Perhaps it will make reasonable the prescription of new antiplatelet drugs, particularly the combination of ticagrelor with aspirin.Aim. To assess the cost-effectiveness of VerifyNow P2Y12 platelet reactivity testing in patients after ACS.Material and methods. The analysis was performed for patients aged 55 years after ACS by modeling based on the results of the PLATO trial considering Russian epidemiological data. The time horizon of simulation was 5 years. It was assumed that the patients were receiving either generic clopidogrel or ticagrelor for 1 year, or before maintenance treatment VerifyNow P2Y12 assay had been performed, and the patients with platelet reactivity index >230 24-48 hours after ACS were receiving ticagrelor and the remaining patients - generic clopidogrel. It was expected that after 1 year the patients would discontinue treatment with clopidogrel or ticagrelor, and hereafter additional therapeutic effect of their use would be absent. The costs of antiplatelet agents in the reference case corresponded to the weighted average price of public procurement in 2013 in Russia. The costs of treatment of complications corresponded to the compulsory health insurance rates for St. Petersburg in 2014. The cost and life expectancy were discounted at 3.5% per year.Results. The platelet reactivity test and the prescription by its results of the combination of clopidogrel plus aspirin or ticagrelor plus aspirin can prevent 5 myocardial infarction and 6 deaths per 1000 patients additionally as compared with the prescription of clopidogrel plus aspirin combination to all patients. The costs for one additional year of life as compared with the combination of clopidogrel plus aspirin were 376.5 and 373.2 thousand rubles, respectively, the costs for one additional quality adjusted life year (QALY) were 433.8 and 509.8 thousand rubles, respectively. The total predictive value of costs per 1 patient with ACS using the test was 32% lower than in the routine use of ticagrelor in all patients.Conclusion. Assessment of platelets reactivity using VerifyNow P2Y12 assay in patients with ACS and modification of antithrombotic therapy in accordance with the received data can be considered as a cost-effective intervention which can reduce treatment costs as compared with the routine use of new antithrombotic drugs.

Ингибитор ароматазы III поколения Фемара – препарат выбора для лечения больных РМЖ с метастазами в кости в менопаузе. Высокая эффективность и безопасность терапии Фемарой продемонстрированы в многоцентровых международных рандомизированных клинических исследованиях. В силу особенностей механизма действия при назначении больным РМЖ в менопаузе Фемара существенно снижает уровень эстрогенов в сыворотке крови. Но, как известно, снижение уровня эстрогенов в сыворотке крови до 5 мг и ниже у больных РМЖ увеличивает риск переломов на 33%, что в свою очередь ведет к увеличению риска смерти. Поэтому в настоящее время в стандарт лечения больных РМЖ с метастазами в кости входят бисфосфонаты. В клинических исследованиях показано, что использование золедроновой кислоты (Зомета) тормозит развитие остеопороза, ингибирует резорбцию кости и снижает частоту осложнений, обусловленных метастазами в кости. У больных РМЖ в менопаузе при назначении Зометы увеличивалась минеральная плотность костной ткани. Кроме того, золедроновая кислота на этапе доклинического изучения продемонстрировала способность индуцировать апоптоз клеток РМЖ и ингибировать пролиферацию не только костных, но и висцеральных (в легких и печени) метастазов. Учитывая изложенное, использование Фемары в комбинации с Зометой у больных РМЖ с метастазами в кости в менопаузе представляется целесообразным. В 2004–2006 гг. проведено российское многоцентровое исследование по изучению эффективности использования Зометы на фоне эндокринной терапии Фемарой больных РМЖ с метастазами в кости. Цель исследования: улучшение результатов лечения больных РМЖ с метастазами в кости. Оценка эффективности и безопасности терапии Фемарой в комбинации с Зометой в первой/второй линии терапии у больных РМЖ с метастазами в кости. Помимо основной задачи исследования – оценки частоты, характера и продолжительности лечебных эффектов – оценивали такие показатели, как время до прогрессирования, частоту и время до развития костных осложнений, влияние терапии на минеральную плотность костной ткани, продолжительность жизни и общую выживаемость больных. Кроме того, определяли динамику активности пациентов, интенсивности болевого синдрома и качества жизни больных. Оценка безопасности терапии предусматривала оценку характера, частоты и степени выраженности побочных эффектов терапии.Комбинация Фемары и Зометы – эффективный и безопасный режим терапии больных РМЖ с метастазами в кости в менопаузе. Использование этого режима позволяет получить объективные ответы в 25% наблюдений, уменьшить частоту развития осложнений, обусловленных метастатическим поражением костей, включая болевой синдром, патологические переломы, снизить потребность в анальгетиках, лучевой терапии и необходимость хирургических вмешательств на костях.