The efficacy and safety study of Mexidol and Mexidol FORTE 250 in patients with chronic cerebral ischemia

Author:
L.A. SHCHEPANKEVICH1,2, YU.A. NIKOLAEV1, E.V. TANEEVA3, M.A. PERVUNINSKAYA1, M.S. SHCHEPANKEVICH1,2

1Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia;
2Novosibirsk State Medical University, Novosibirsk, Russia;
3State Novosibirsk Regional Clinical Hospital, Novosibirsk, Russia

Summary:
Objective. To study the efficacy and safety of sequential MexidoL therapy, administered intravenously (500 mg once a day) for 14 days, followed by taking the oral form Mexidol FORTE 250 at a dose of 250 mg (1 tablet) 3 times a day for 60 days in elderly patients with chronic cerebral ischemia (CCI) on the background of arterial hypertension and atherosclerosis. Material and methods. An open prospective observational study included 60 patients with an established diagnosis (CCI), confirmed by the results of neuroimaging. All patients were examined with an assessment of neuropsychological status (MoCA test), severity of asthenia (scale MFI-20), emotional state (Hamilton anxiety and depression scale), motor functions (formalized clinical scale for assessing motor activity of elderly Tinetti). The effectiveness of the therapy was evaluated according to the quality of life questionnaire (SF-36). Results. The results of the study showed the high efficiency and safety of sequential therapy with Mexidol in relation to the relief of asthenic and emotional disorders, improving the state of cognitive functions, improving the quality of life of patients. The maximum effect occurred after the end of the full course of therapy. High adherence of patients to the therapy, low frequency of adverse events are shown. Conclusion. Sequential use of intravenous administration of Mexidol followed by oral administration of Mexidol FORTE 250 is an effective and safe way to treat patients with CCI. Keywords: chronic cerebrovascular disease, arterial hypertension, atherosclerosis, ethylmethylhydroxypyridine succinate, mexidol, mexidol forte 250, cognitive impairment.


Results of an international multicenter, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of sequential therapy with Mexidol and Mexidol FORTE 250 in patients with chronic brain ischemia (MEMO)

Author:
A.I. FEDIN1, V.V. ZAKHAROV2, M.M. TANASHYAN3, E.I. CHUKANOVA1, E.N. MADZHIDOVA4, L.A. SHCHEPANKEVICH5,6, O.D. OSTROUMOVA7

1Russian National Research Medical University named after N.I. Pirogov, Moscow, Russia;
2Sechenov First Moscow Medical University (Sechenov University), Moscow, Russia;
3Scientific Center of Neurology, Moscow, Russia;
4Tashkent Pediatric Medical Institute, Tashkent, Republic of Uzbekistan;
5Novosibirsk State Medical University, Novosibirsk, Russia;
6Federal Research Center for Fundamental and Translational Medicine, Novosibirsk, Russia;
7Russian Medical Academy of Continuous Professional Education, Moscow, Russia

Summary:
Objective. To assess the efficacy and safety of sequential therapy with Mexidol solution for intravenous and intramuscular administration, 50 mg/ml and Mexidol FORTE 250 film-coated tablets, 250 mg in patients with chronic brain ischemia (CBI). Material and methods. An international multicenter, randomized, double-blind, placebo-controlled trial, conducted in 15 clinical centers located in Russian Federation and Republic of Uzbekistan, included 318 patients with CBI aged 40 to 90 years. The patients were randomized into 2 groups, the patients of the 1-st group received Mexidol intravenously 500 mg once daily for 14 days, followed by Mexidol FORTE 250 — 250 mg 3 times a day orally for 60 days; patients of the 2-nd group received a placebo in a similar mode. The primary endpoint was the mean value of difference by MoCA scale at the point of completing the therapy comparing to initial value. Results. According to the results of the assessment of the primary endpoint, statistically significant changes in the MoCA scores at the stage of completion of study were revealed when comparing the dynamics between the 1-st and 2-nd groups (p<0.000001). The lower limit of the 95% confidence interval for the difference in the average of the main efficacy endpoint between the 1-st and 2-nd groups was 1.51, which allows to state a higher efficacy of the use of Mexidol. According to the estimates of secondary endpoints, a statistically significant advantage over placebo at the last visit achieved while evaluation by the following scales and tests: digit symbol substitution test, MFI-20 asthenia assessment scale, Beck anxiety scale, Vane questionnaire, Tinetti scale, SF-36 questionnaire (mental component of health), CGI scale. The comparable nature of the safety profile of Mexidol and Placebo was established. Conclusion. The validity and expediency of the use of Mexidol and Mexidol FORTE 250 in the treatment of patients with CBI has been demonstrated. Keywords: chronic brain ischemia, cognitive impairment, neuropsychological testing, ethylmethylhydroxypyridine succinate, Mexidol, Mexidol FORTE 250, treatment of CBI, MEMO trial.


Features of responding to stress of elderly patients with chronic brain ischemia

Author:
T.A. SLYUSAR, YU.V. ABRAMENKO, S.S. RUBINA, R.V. MAYOROV, I.N. SLYUSAR

Tver State Medical University, Tver, Russia

Summary:
The aim of the study. To study the peculiarities of responding to stress, the stress resistance and adaptation of older men and women with chronic brain ischemia, as well as the stressboard effect of Mexidol. Material and methods. 124 patients aged 60–74 years old are surveyed: 72 men and 52 women (average age, respectively, 65.3 ± 0.4 and 64.7 ± 0.7 years) with Chronic Brain Ischemia I–II stage against the background of arterial hypertension and its combinations with atherosclerosis of cerebral vessels. The level of psychosocial stress was determined on the Holmes-Ray scale. Features of the response of patients to stress was studied using the methodology Scale of Psychological Stress PSM‑25 and S. Rogenzweig. Stress resistance was investigated using S. Kuhlen's stress resistance self-resistant test and Villianson. The level of anxiety was determined using a scale of Ch. D. Spilberger and Yu. L. Khanin, depressed – backup questionnaire. The type of adaptation reactions was studied in the leukocyte blood formula on the percentage ratio of lymphocytes and segmented neutrophils, taking into account the representation of other formed elements. Results. The level of stress in older women with Chronic Brain Ischemia was higher than in men. The predominance of the intrinsic orientation of the reaction to stress and resolving the type of response to men, and the extrapunitive or self-defense type among women, which may indicate the largerness of the latter. The level of stress resistance was lower in women than in men, which correlated with higher indicators of situational anxiety. Adverse adaptation reactions were more often registered in women than in men. The course of treatment with Mexidol of elderly patients with chemical leads to a decrease in the severity of subjective and objective symptoms, alarming disorders, increases the stress resistance and adaptive capabilities of the body, which is confirmed by an increase in the number of persons with favorable adaptation reactions. The high efficiency and safety of sequential therapy with Mexidol (injections, then the tableted form of Mexidol Forte 250) is shown. Keywords: chronic brain ischemia, sex, stress, stress resistance, emotional disorders, anxiety, depression, Mexidol, adaptation reactions.


The efficacy of antioxidant treatment with mexidol forte in 250 patients with chronic cerebral venous insufficiency

Author:
E.I. CHUKANOVA, A.S. CHUKANOVA, KH.I. MAMAEVA
Pirogov Russian National Research Medical University, Moscow, Russia

Summary:
Objective. To study the efficacy and safety of complex treatment with 2-ethyl-3-hydroxy-6-methylpyridine (mexidol forte 250) and venotonic drugs L-lysine aescinat and diosmin/hesperidin in patients with chronic cerebral venous insufficiency (CCVI). Material and methods. One hundred and twenty CCVI patients with clinical and ultrasonic signs of cerebral venous discirculation were studied. Patients were stratified into group 1 (n=40) treated perorally with mexidol forte 250 and diosmin/hesperidin during 74 days in combination with two courses of L-lysine aescinat intravenously on the 1st and 30th days from baseline, group 2 (n=40) treated with mexidol forte 250 and diosmin/hesperidin during 74 days, group 3 (n=40) treated perorally with diosmin/hesperidin during 74 days. Results and conclusion. The efficacy and safety of the complex treatment of CCVI patients with venotonic drugs with the inclusion of mexidol forte 250 at a dose of 750 mg/day for 74 days is shown. The study demonstrates a significant positive effect of mexidol forte 250 on the dynamics of complaints and indicators of the neurological and psychoemotional status of patients. Monotherapy with the venotonic drug diosmin/hesperidin shows its insufficient efficacy. Keywords: chronic cerebral venous insufficiency, antioxidants, mexidol forte 250, venotonic drugs, L-lysine aescinat, diosmin/hesperidin.


Possibilities of improving the effectiveness of therapy in patients with chronic cerebral ischemia against the background of COVID-19

Author:
V.V. KOVALCHUK, I.I. ERSHOVA, N.V. MOLODOVSKAYA
Semashko City Hospital No. 38, St. Petersburg, Russia

Summary:
Objective. To study the possibility of improving the efficacy of treatment with mexidol in COVID‑19 patients with chronic cerebral ischemia (CCI). Material and methods. Three hundred and four patients with CCI and COVID‑19 were observed, group 1 (n=152) consisted of patients receiving basic therapy and mexidol, group 2 (n=152) received only basic therapy. Mexidol was administered intravenously for 14 days, 500 mg (10 ml) per 400 ml of saline solution, then Mexidol FORTE 250 was administered in a dose of 250 mg 3 times a day for 2 months. The state of cognitive functions (MoCA scale), sleep (Spiegel questionnaire), asthenia (MFI-20 scale), and quality of life (SIP questionnaire) were evaluated. Examinations were performed before treatment, 30 and 75 days after start of treatment. Results. In group 1, there was a more complete and earlier recovery of the state of cognitive functions (an increase in indicators on the MoCA scale, p<0.01), a regression of asthenia (p<0.05), and normalization of sleep (p<0.01). By the end of the study, there were significantly more patients in group 1 with complete or significant recovery of all quality of life indicators. Conclusion. Long-term sequential therapy with mexidol provides a more complete recovery of impaired functions in patients with CCI and COVID-19. Keywords: COVID-19, SARS-CoV-2, chronic cerebral ischemia, asthenia, cognitive disorders, dementia, quality of life, mexidol.


Effect of Mexidol on the quality of life and functional status of patients with chronic cerebral ischemia and chronic heart failure with reduced left ventricular ejection fraction

Author:
V.V. TOLKACHEVA1, E.R. KAZAKHMEDOV1, ZH.D. KOBALAVA1, S.A. GALOCHKIN1, A.V. SHCHULKIN2

1Peoples’ Friendship University of Russia, Moscow, Russia;

2Pavlov Ryazan State Medical University, Ryazan, Russia

Summary:
Objective. To study the effect of Mexidol on the functional state of myocardium, NT-proBNP level, exercise tolerance, quality of life, severity of oxidative stress, inflammatory response and endothelial dysfunction in patients with chronic brain ischemia and chronic heart failure NYHA class II-III in a 13-week sequential (intravenous and oral) therapy with Mexidol® and standard therapy. Material and methods. The study included 44 patients with chronic brain ischemia and chronic heart failure NYHA class II—III. Mean age was 65.5±11.8 years, men accounted 75%. The group of Mexidol + standard therapy of chronic heart failure included 21 patients, the group of standard therapy — 23 patients. Echocardiography parameters, exercise tolerance test (six minute walk test, SMWT), patient’s clinical condition according to SHOKS scale (modification by V. Yu. Mareev), NT-proBNP concentration, markers of oxidative stress (malonic dialdehyde (MDA), superoxide dismutase (SOD)), inflammatory reaction (C-reactive protein (CRP), tumor necrosis factor α (TNFα)), homocysteine and cystatin C were examined initially, after 7 days and 13 weeks. The quality of life was assessed initially and at the end of the study using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) and the Kansas City Cardiomyopathy Questionnaire (KCCQ). Results. «Mexidol + standard therapy» group was characterized by more significant improvement in the quality of life, better SMWT data and SHOKS scores, significant decrease in end-diastolic and end systolic LV dimensions, as well as NT-proBNP level after 7 days and 13 weeks compared to the basic therapy group. Mexidol administration reduced MDA concentration and increased SOD activity after 7 days and 13 weeks. We also observed a significant decrease in CRP and TNFα levels after 7 days and 13 weeks in the same group. Less augmentation of homocysteine was revealed in the Mexidol therapy group. There were no significant between-group differences in cystatin C levels. Conclusion. Mexidol in addition to standard therapy of chronic brain ischemia and chronic heart failure class II-III has a favorable effect on the quality of life, functional status, improves clinical condition and intracardiac circulation, decreases concentration of NT-proBNP, promotes antioxidant activity, reduces inflammatory reaction, slows down increase of homocysteine and does not influence kidney function. Keywords: chronic brain ischemia, heart failure, quality of life, cognitive status, oxidative stress, ethyl-methyl-hydroxypyridine succinate, Mexidol, inflammation, endothelial dysfunction.


The efficacy of ethylmethylhydroxypyridine succinate in patients with cerebrovascular pathology complicated with diabetes mellitus and metabolic syndrome

Author:
E.V. EKUSHEVA1,2, E.V. BIRYUKOVA3
1Academy of Postgraduate Education under the Federal State Budgetary Unit «Federal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of the Federal Medical Biological Agency», Moscow, Russia;
2Belgorod State National Research University, Belgorod, Russia;
3Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia

Summary:
Arterial hypertension, diabetes mellitus, obesity and dyslipidemia continue to be the main risk factors for diseases of the circulatory system and the leading causes of mortality in the world, the combination of these diseases significantly increases the likelihood of the development and more rapid progression of cardiovascular and cerebrovascular pathology. Improving approaches to the diagnosis and treatment of these diseases is a priority problem in modern medicine. Currently, there is no universal drug that can influence all stages of pathological process in both cerebrovascular diseases and diabetes mellitus, and the problem of rational use of drugs in patients with comorbid pathology has not been completely resolved. A difficult clinical task includes not only the timely detection of the disease and the correct diagnosis, but also the choice of the safest and most effective medicine. A number of clinical studies have demonstrated the efficacy of mexidol in the treatment of this category of patients, which is determined by its complex, pleiotropic and multimodal mechanisms of action. Keywords: cerebrovascular diseases, diabetes mellitus, metabolic syndrome, antioxidant therapy, mexidol.


Effectiveness and safety of mexidol forte 250 in the sequential therapy in patients with chronic ischemia

Author:
N.G. KATAEVA1, T.A. ZAMOSHCHINA1,2, M.V. SVETLIK1,2
1 Siberian State Medical University , Tomsk, Russia;
2 National Research Tomsk State University , Tomsk, Russia

Summary:
Objective. To study of efficacy and safety of mexidol used as intravenous infusion for 14 days, followed by per os treatment with mexidol FORTE 250 for 60 days in patients with chronic brain ischemia (CHM) complicated with arterial hypertension and atherosclerosis. Material and methods. The mexidol group included 27 patients (24 women and 3 men) with CHM I—II gr and the combination of arterial hypertension and atherosclerosis who received intravenous infusions of mexidol (500 mg once daily) within 14 days, with the subsequent per os treatment with mexidol FORTE 250 in a daily dose of 750 mg (1 tablet 3 times a day) for 60 days. The comparison group consisted of 30 patients (22 women and 8 men) with CHM I—II gr, comparable in age, nature of risk factors and expression of neurological manifestations. Patients in both groups received basic medications to treat their risk factors. Motor activity (Tinetti test), cognitive functions (MoCa test), anxiety and depression (Hamilton anxiety and depression scale), clinical condition (General Clinical Impression scale) were assessed. Results and conclusion. Inclusion of mexidol (500 mg iv infusion once a day within 14 days with the subsequent oral administration of 750 mg (1 tablet 3 times a day) for 60 days) in standard therapy of arterial hypertension with atherosclerosis and chronic brain ischemia is expedient. The results show greater clinical efficacy and sufficient safety of such combination therapy. By the end of therapy (day 74), patients in the mexidol group have a reliable improvement in motor activity, cognitive function and psychoemotional sphere, as well as a decrease in fatigue and neurological manifestations compared with the comparison group. Keywords: chronic ischemia of a brain, mexidol, mexidol FORTE 250.


Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with chronic cerebral ischemia

Author:
M.V. ZHURAVLEVA1,2, A.B. PROKOFIEV1,2, S.YU. SEREBROVA1,2, N.S. VASYUKOVA3, E.YU. DEMCHENKOVA1, V.V. ARKHIPOV1
1Scientific Center for Examination of Medical Devices, Moscow, Russia;
2Sechenov First Moscow State Medical University, Moscow, Russia;
3Federal Scientific Center-all-Russian Research Skriabin and Kovalenko Institute of Experimental Veterinary Medicine the Russian Academy of Sciences, Moscow, Russia

Summary:
Chronic cerebral ischemia (CCI) is a common cerebrovascular syndrome, the development of which is associated with a high risk of increasing cognitive, behavioral, and motor disorders, and the formation of a patient’s dependence on others. Timely start of treatment can slow down the course of the disease, make it more favorable. The review considers the possibility of using the domestic neuroprotector mexidol in patients with CCI. The results of a series of clinical studies on the use of ethylmethylhydroxypyridine succinate (mexidol) in patients with CCI are analyzed. The effectiveness of the drug in relieving cognitive, affective and motor disorders is noted. Information about the good tolerance of mexidol is presented. Keywords: chronic brain ischemia, cognitive disorders, affective disorders, ethylmethylhydroxypyridine succinate, Mexidol, treatment.


The role of oxidative stress in the development of vascular cognitive disorders

Author:
A.N. BOGOLEPOVA
Pirogov Russian National Research Medical University, Moscow, Russia;
Federal Center of Brain Research and Neurotechnologies, Moscow, Russia

Summary:
Vascular cognitive impairment (VCI) is one of the most serious problems of clinical neurology, being the second most common cause of dementia. VCI covers a range of disorders in which vascular factors cause or contribute to cognitive decline. Among the main risk factors for VCI are old age and vascular factors, which lead to endothelial dysfunction and damage, which, in turn, can cause neurovascular dysfunction, increased permeability of the blood-brain barrier, and microvascular thrombosis. Oxidative stress is one of the most important mechanisms for the development of VCI that indicates the need for the use of agents with antioxidant activity. One of these drugs is ethylmethylhydroxypyridine succinate (mexidol). Mexidol is a drug with marked antioxidant and antihypoxic activities. The clinical efficacy of mexidol in relation to VCI has been demonstrated in many studies. Keywords: chronic cerebrovascular insufficiency, oxidative stress, vascular cognitive impairment, endothelial dysfunction, mexidol.