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.
Efficacy and safety of ethylmethylhydroxypyridine succinate in patients with ischemic stroke
Author:
M.V. ZHURAVLEVA1,2, I.A. SHCHUKIN3, M.S. FIDLER3, A.B. PROKOFIEV2, S.YU. SEREBROVA2, N.S. VASYUKOVA4, E.YU. DEMCHENKOVA1, V.V. ARKHIPOV1,2
1Research Centre for Examination of Medical Devices, Moscow, Russia;
2Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
3Pirogov Russian National Research Medical University, Moscow, Russia;
4Federal Scientific Center — All-Russian Scientific Research Institute of Experimental Veterinary Medicine named after K.I. Skryabin and Ya.R. Kovalenko, Moscow, Russia
Summary:
Stroke is still the most significant problem of the modern medicine and the leading cause of mortality and morbidity. There is the great experience of neuroprotection in patients with stroke in the Russian Federation. In clinical practice it’s important to follow conditions, where neuroprotection will have maximum safety and effectiveness. The clinical trials of ethylmethylhydroxypyridine succinate (mexidol) in patients with acute ischemic stroke are described in the present review. Early management (in the first 6 hours) with mexidol significantly improve recovery dynamic and stroke outcome. Therapy with mexidol increases neurological recovery, improves vital activity and quality of life of patients with stroke. Furthermore, mexidol demonstrates high safety profile. Keywords: ischemic stroke, thrombolytic therapy, clinical trial, disability, antioxidant system, ethylmethylhydroxypyridine succinate, Mexidol.
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.
The trial of the efficacy and safety of sequential therapy with mexidol forte 250 in acute and early recovery stages of hemispheric ischemic stroke
Author:
M.A. LOSKUTNIKOV, M.A. DOMASHENKO, T.M. VAKIN, I.A. TRUSHINA, V.I. KONSTANTINOV, O.S. PROSKURYAKOVA, E.P. SHCHUKINA
Magnitogorsk Irong&Steel Clinical Hospital, Magnitogorsk, Russia
Summary:
Objective. To evaluate the efficacy and safety of sequential therapy with mexidol (solution for intravenous and intramuscular injections) and mexidol forte 250 (coated tablets) in acute and early recovery stages of hemispheric ischemic stroke. Material and methods. The changes in scores on the modified Rankin Scale (mRs) (primary endpoint), the National Institute of Health Stroke Scale (NIHSS), the Bartel Index (BI), the Montreal Cognitive Assessment (MoCa), the Beck Depression Inventory (BDI), the EuroQol Quality of Lifes Scale ( EQ–5D) were assessed in the end of treatment (secondary endpoint). Results and Conclusion. Prolonged and sequential therapy with mexidol at the dose 500 mg daily during 14 days (saturation phase) and mexidol forte 250 at the dose of 250 mg three times a day during 60 days (maximum therapeutic effect) provides additional opportunities for a more complete recovery in acute and early recovery stages of hemispheric ischemic stroke (increases quality of life, improves movement and cognitive functions). Keywords: hemispheric ischemic stroke, mexidol forte 250, acute and early recovery stages, quality of life.
Efficacy and safety of Mexidol across age groups in the acute and early recovery stages of hemispheric ischemic stroke (results of additional sub-analysis of a randomized double blind multicenter placebo-controlled study, in parallel groups trial EPICA)
Author:
L.V. STAKHOVSKAYA1, E.A. MKHITARYAN2, O.N. TKACHEVA1,2, T.M. OSTROUMOVA3, O.D. OSTROUMOVA3,4
1Pirogov Russian National Research Medical University, Moscow, Russia;
2Russian Clinical and Research Center of Gerontology of Pirogov Russian National Research Medical University, Moscow, Russia;
3Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical (Sechenov University),
Moscow, Russia;
4Russian Medical Academy of Continuous Professional Education, Moscow, Russia
Summary:
Aim. To evaluate the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (IS) across age groups according to the World Health Organization classification. Material and methods. The study is an additional analysis across age groups among patients participated in the randomized double blind multicenter placebo-controlled, in parallel groups trial EPICA. All subjects (62 men and 88 women) were subdivided into age groups: younger than 60 years, 60—65 years, 76—90 years. Additionally, all participants were divided into 2 populations: ITT (Intent to treat population, patients who received at least one treatment/placebo dose) and PP (Per protocol population, patients who received treatment per study protocol). Results of Modified Rankin scale (mRs) at the end of treatment period, Barthel index, Beck depression inventory, European Quality of Life Questionnaire were assessed. Results. The efficacy of mexidol assessed with all the scales did not differ depending on the age group. By the end of treatment, the mean mRS score was lower in the 76-90 years subgroup (in both populations), compared to placebo (p<0,001). The decrease in mean mRS score (Visit 1—5) was more prominent in patients aged 60—65 years (p=0,025), including patients with diabetes mellitus (DM). Patients aged 76—90 years and patients with DM, compared to placebo, had a decrease of the severity of cognitive-affective depression symptoms (p=0,049 and p=0,02) and an increase in patients without problems with everyday activities (p=0,007 and p=0,02). Patients with DM, compared to placebo, also had the higher levels of everyday activity (p=0,023) and quality of life (p=0,045). There were no statistically significant differences in the frequency of side-effects in patients of all groups. Conclusion. It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages in all age groups, including patients with DM. Keywords: ischemic stroke, mexidol, ethylmethylhydroxypyridine succinate, efficacy and safety, ischemic stroke, acute period, acute rehabilitation period, EPICA.
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.
Mexidol® and Mexidol® FORTE 250 in consecutive therapy of cognitive disorders in comorbid patients with joint pathology on the background of arterial hypertension and ischemic heart disease
Author:
L.N. ELISEEVA, S.V. KARTASHOVA
Kuban State Medical University of the Ministry of Healthcare of Russia, Krasnodar
Summary:
The aim of the study was to assess the efficacy, safety and possibility of correcting the neuropsychiatric manifestations of chronic cerebral ischemia (CCI) by Mexidol® on the background of arterial hypertension (AH), atherosclerosis (IHD), osteoarthritis (OA) or rheumatoid arthritis (RA). Material and methods. We examined 134 patients 45–75 years old with neurovizualized CCI, combined with hypertension, coronary artery disease, and joints pathology. Group 1 (observation) included 79 patients – 30 patients with RA (subgroup 1А) and 49 patients with OA of knee joints (subgroup 1B), who got Mexidol® in their complex therapy. Group 2 (control) consisted of 30 patients – 25 patients with RA (subgroup 2A) and patients with OA (subgroup 2B), who got basic therapy without Mexidol® addition. The dynamics of subjective and physical symptoms, values on the CGI, MoCA, MFI 20 scales, anxiety and depression scales of Hamilton and Tinnetti were estimated. Mexidol® was administered intravenously (500 mg per day) for 14 days, followed by oral administration of Mexidol® FORTE 250 by 250 mg 3 times/day for another 60 days. Results. On the background of constant standard complex therapy, an increasing improvement was revealed in all studied indexes in cases of additional use of Mexidol®. In control groups, the cognitive status did not change. The use of initiating intravenous therapy with Mexidol® increased the adherence of patients to long-term use of the drug. Conclusion. Locomotor dysfunctions in polymorbid patients are partially associated with CCI. The additional appointment of sequential infusion and tablet forms of Mexidol® significantly improves cognitive functions with the correction of walking stability, asthenic manifestations, and increases motivation for active life. Key words: chronic cerebral ischemia, Mexidol®, osteoarthritis, rheumatoid arthritis, arterial hypertension, ischemic heart disease.
Results of a Randomized, Double-Blind, Multicenter, Placebo-Controlled, Parallel-Group Study of the Efficacy and Safety of Mexidol in Prolonged Sequential Therapy of Patients in the Acute and Early Recovery Stages of Hemispheric Stroke (the EPICA study)
Author:
L. V. Stakhovskaya1, N. A. Shamalov1, D. R. Khasanova2, E. V. Mel’nikova3, A. S. Agaf’ina4, K. V. Golikov5, E. I. Bogdanov6, A. A. Yakupova6, L. V. Roshkovskaya7, L. V. Lukinykh8, T. M. Lokshtanova9, I. E. Poverennova10, and L. A. Shchepankevich11
1 Research Institute of Cerebrovascular Pathology and Stroke, Pirogov Russian National Research Medical University, Russian Ministry of Health, Moscow, Russia; e-mail: lstakh@mail.ru.
2 Interregional Clinical Diagnostic Center, Kazan, Russia.
3 St. Petersburg City Clinical Hospital No. 26, St. Petersburg, Russia.
4 St. Petersburg City Clinical Hospital No. 40 of the Resort Administrative District, St. Petersburg, Russia.
5 St. Petersburg City General Hospital No. 2, St. Petersburg, Russia.
6 Kazan Sate Medical University, Russian Ministry of Health, Kazan, Russia.
7 Nikolaevskaya Hospital, St. Petersburg, Russia.
8 Vsevolzhsk Clinical Interregional Hospital, Leningradskaya Oblast, Russia.
9 Pirogov City Clinical Hospital No. 1, Samara, Russia.
10 Seredavin Samara Regional Clinical Hospital, Samara, Russia.
11 Research Institute of Experimental and Clinical Medicine, Novosibirsk, Russia.
Summary:
Objectives. To assess the effi cacy and safety of prolonged sequential therapy with Mexidol in patients with hemispheric ischemic stroke (IS) in the acute and early recovery phases. Materials and methods. A randomized, double-blind, multicenter, placebo-controlled, parallel-group study included 151 patients (62 men and 89 women) was performed in which 150 patients (62 men and 88 women) aged 40–79 years were randomized. Simple randomization was used to defi ne two groups: patients of group 1 received Mexidol therapy at a dose of 500 mg/day by intravenous infusion for 10 days followed by oral doses of 1 tablet (125 mg) three times a day for eight weeks. Patients of group 2 received placebo by the same protocol. The duration of involvement in the trial was 67–71 days. Results. At the end of treatment, mean scores on the modified Rankin scale (mRS) were lower in group 1 than group 2 (p = 0.04). Decreases in mean mRS scores (at visits 1–5) were more marked in group 1 (p = 0.023). The proportion of patients achieving recovery corresponding to 0–2 points on the mRS (at visit 5) was signifi cantly greater in group 1 (p = 0.039). Testing on the National Institutes of Health Stroke Scale at visit 5 gave a signifi cantly lower score in group 1 (p = 0.035). Decreases in scores on the National Institutes of Health Stroke Scale at the end of treatment relative to the baseline level in patients with diabetes mellitus were more marked in group 1 (p = 0.038). In group 1, the total population and the subpopulation of patients with diabetes mellitus showed more marked improvements in quality of life, which was apparent by visit 2. The proportion of patients without diffi culty mobilizing was signifi cantly greater in group 1 (p = 0.022). There were no signifi cant differences in the frequencies of adverse events in patients of the two groups. Conclusions. Use of Mexidol in the acute and early recovery phases of IS is recommended. Keywords: acute cerebrovascular accident, Mexidol, ethylmethylhydroxypyridine succinate, effi cacy and safety, ischemic stroke, acute phase, early recovery phase, EPICA.