Possibilities of multimodal neuroprotection in patients with chronic cerebral ischemia on the background of arterial hypertension and atherosclerosis
Author:
GRIBACHEVA I.A., POPOVA T.F., PETROVA E.V., ZVONKOVA A.V.
Novosibirsk State Medical University, Ministry of Health of Russia, Novosibirsk
Summary:
Chronic cerebrovascular pathology is manifested by a combination of cognitive, emotional and autonomic disorders. Correct and timely assessment and accurate diagnosis of emotional and autonomic disorders and their timely correction are important, among other things, for slowing down the progression of cognitive deficits. Objective: to study the efficacy and safety of Mexidol administered intravenously by drip infusion (500 mg 1 time per day) for 14 days, followed by oral administration of the drug Mexidol FORTE 250 at a dose of 250 mg 3 times a day for 60 days in middle-aged patients with chronic cerebral ischemia (CCI) on the background of arterial hypertension and atherosclerosis. Material and methods. The open observational program included 60 patients aged 45 to 59 years with CCI, confirmed by the results of a neuropsychological and neuroimaging examination. Patients received Mexidol first intravenously (14 days), and then orally in pills – Mexidol FORTE 250 (60 days). Patients underwent neuropsychological testing, assessment of the level of reactive and personal anxiety (Spielberger–Khanin scale), of vegetative disfunction (A.M. Wayne's autonomic response scale modified by V.L. Golubev), of the severity of general, mental and physical asthenia (MFI-20) and quality of life (MOS SF-36 questionnaire). Results. The results of the treatment made it possible to establish relief of asthenic syndrome and vegetative dysfunction on the background of Mexidol use. The differences were statistically significant both when comparing with the baseline and with the comparison group (p<0.05). The use of Mexidol was accompanied by a decrease in the severity of complaints and subjective symptoms. The combination of positive effects led to an increase in indicators of quality of life (p<0.05). The treatment was well tolerated. Conclusion. Patients with CCI have significant emotional, vegetative and asthenic disorders. The use of Mexidol can reduce the severity of these disorders, which gives reason to recommend it for the treatment of such patients. Keywords: chronic cerebral ischemia; arterial hypertension; atherosclerosis; cognitive impairment; vegetative disorders; asthenia; Mexidol; Mexidol FORTE 250.
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): subanalysis in patients with arterial hypertension
Author:
ZAKHAROV V.V.1, OSTROUMOVA O.D.1,2, KOCHETKOV A.1,2, KLEPIKOVA M.V.2, FEDIN A.1,3
1I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University)
2Russian Medical Academy of Continuous Professional Education of the Ministry of Healthcare of Russia, Moscow
3N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia, Moscow
Summary:
Abstract. Chronic brain ischemia (CBI) is one of the most common neurological disorders in clinical practice. Objective: to evaluate the efficacy and safety of sequential therapy with Mexidol® solution intravenously and Mexidol® FORTE 250 film-coated tablets, 250 mg orally in patients with and without arterial hypertension (AH) in terms of the drug effect on cognitive functioning, as well as the severity of asthenic, anxiety, vegetative and motor disorders, and quality of life in CBI. Material and methods. In a subanalysis patients with CBI were divided into four subgroups: 1st – AH patients receiving Mexidol® and Mexidol® FORTE 250 (n=144); 2nd – AH patients receiving placebo (n=146); 3rd – patients without AH receiving Mexidol® and Mexidol® FORTE 250 (n=15); 4th – patients without AH receiving placebo (n=12). Results. At the end of the follow-up, significant differences were found in the dynamics of the MoCA scores between the patients receiving Mexidol® and placebo (p=0,000), which allows to state a superior efficacy of Mexidol in the subgroup of patients with AH. Also in the long-term sequential therapy with Mexidol®, in contrast to the placebo, the median value of the MoCA score at the end of the follow-up reached normal levels in patients with and without AH. When assessing secondary efficacy endpoints, a significant advantage of Mexidol® over placebo in the population of patients with AH at the end of follow-up was achieved on the following parameters: The Digit Symbol Substitution Test, MFI-20, the Beck Anxiety Inventory, Tinetti Performance-Oriented Mobility Assessment, psychological component of health according to SF-36 questionnaire. A comparable character of the safety profile of Mexidol® and placebo was established. Conclusion. The obtained results allow to recommend the use of long-term sequential therapy with Mexidol in the complex therapy of patients with AH and CBI as a tool for the brain protection as a AH target organ and as a tool of pathogenetically substantiated therapy of cognitive, emotional, asthenic, vegetative and motor disorders. Key words: chronic brain ischemia, arterial hypertension, cognitive impairment, ethylmethyhydroxypyridine succinate, Mexidol®, Mexidol® FORTE 250.
Improving the effectiveness of pharmacotherapy in comorbid patients with chronic cerebral ischemia on an outpatient basis
Author:
T.L. VIZILO1, E.G. AREFIEVA2
1Kemerovo State Medical University, Kemerovo, Russia;
2Barbarash Kuzbass Clinical Cardiological Dispensary , Kemerovo, Russia
Summary:
Objective. To study the efficacy and safety of sequential therapy with Mexidol (500 mg 1 time/day for 14 days intravenously) and Mexidol FORTE 250 (Mexidol FORTE 250 for 250 mg 3 times/day, 60 days) in patients with chronic cerebral ischemia (CCI) on an outpatient basis. Material and methods. The open comparative study included 56 patients aged 46—74 years, age — 60.5+7.9 years. In all patients, the diagnosis of CCI was confirmed by clinical and neuroimaging methods. Patients of group 1 (n=28) received basic therapy and Mexidol, group 2 (n=28) received only basic therapy. Results. Against the background of therapy in patients of group 1, there was a statistically significant improvement in the state of cognitive functions, a decrease in the severity of symptoms of depression and anxiety, manifestations of asthenia. The treatment was characterized by good tolerability, absence of adverse events and cases of drug interactions. Conclusion. Sequential therapy with Mexidol and Mexidol FORTE 250 drugs provides relief of the main clinical manifestations of CCI, is characterized by good tolerability and safety. Keywords: chronic cerebral ischemia, arterial hypertension, ethylmethylhydroxypyridine succinate, Mexidol, Mexidol FORTE 250.
Results of clinical studies of the efficacy and safety of the use of ethylmethylhydroxypyridine succinate in patients with chronic cerebral ischemia
Author:
M.V. ZHURAVLEVA1,2, P.R. KAMCHATNOV3, N.S. VASYUKOVA4, V.V. ARKHIPOV1, E.V. KUZNETSOVA5, T.R. KAMENEVA6, S.YU. SEREBROVA1,2
1Research Center 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;
4Skriabin and Kovalenko Institute of Experimental Veterinary Medicine, Moscow, Russia;
5Research Institute for Healthcare and Medical Management, Moscow, Russia;
6Konchalovsky City Clinical Hospital, Moscow, Russia
Summary:
Chronic cerebral ischemia (CCI) is a common syndrome that, in the absence of adequate therapy, is characterized by a progressive course, an increase in cognitive, emotional, motor and other disorders, eventually leading to persistent disability of the patient. In the treatment of patients with CCI, the use of drugs with a multimodal neuroprotective effect is indicated. The results of the analysis of a series of clinical trials of the drugs Mexidol and Mexidol FORTE in patients with CCI are presented. The effects in relation to cognitive, emotional, asthenic, vegetative and other manifestations of CCI are considered. It is concluded that it is advisable to consistently use the drugs Mexidol and Mexidol FORTE in such patients. Keywords: chronic cerebral ischemia, cognitive impairment, Mexidol, emotional disorders, treatment.
Efficacy of Mexidol in patients with chronic brain ischemia and cognitive impairment of different age groups (results of sub-analysis of the international multicenter, randomized, double-blind, placebo-controlled study of sequential therapy in patients with chronic brain ischemia MEMO)
Author:
V.V. ZAKHAROV1, O.N. TKACHEVA2,3, E.A. MKHITARYAN2,3, A.I. FEDIN2
1Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
2Pirogov Russian National Research Medical University , Moscow, Russia;
3Russian Clinical and Research Center of Gerontology, Pirogov Russian National Research Medical University , Moscow, Russia
Summary:
Objective. To assess the efficacy of sequential therapy with Mexidol and Mexidol FORTE 250 in comparison with placebo in patients of different age groups with chronic brain ischemia. Material and methods. The study is sub-analysis of data of the international multicenter, randomized, double-blind, placebo-controlled study of sequential therapy in patients with chronic brain ischemia (MEMO), which included 318 patients (25% men) in the age of 40—90 (median 60) years. All subjects were subdivided into 3 age subgroups: 40—60 years (n=163), 61—75 years (n=141) and 76—90 years (n=13). The primary efficacy endpoint was the dynamic of increase of total score by MoCA scale, i.e. the absolute value of difference by MoCA scale at the point of day 75 comparing to values before treatment. As secondary efficacy endpoints results of dynamic by following questionnaires and scales were used: digit symbol substitution test, the Health Survey SF-36, asthenia subjective assessment scale (MFI-20), Vane questionnaire, Beck anxiety scale, Tinetti scale. Results. After 75 days of treatment positive dynamic was revealed in cognitive, emotional and motor impairment in patients of 40—60 and 61—75 age subgroups both in groups of Mexidol and placebo, but in group of Mexidol the changes were more prominent which is proved by significantly higher values of median of absolute difference of total score of studied parameters. Conclusion. The results of trial showed that in patients of different age-subgroups with chronic brain ischemia the improvement in cognitive, motor impairment and quality of life, as well as decrease in vegetative impairment, asthenia and anxiety are observed after 75 days of treatment both in Mexidol and placebo group, but in Mexidol group these changes are more prominent. The data obtained confirm the expediency of the use of sequential therapy with Mexidol and Mexidol FORTE 250 in patients of different age subgroups with chronic brain ischemia. Keywords: cognitive impairment, chronic brain ischemia, Mexidol , Mexidol FORTE 250, ethylmethylhydroxypyridine succinate, MEMO trial.
Safety of Mexidol® (ethylmethylhydroxypyridine succinate) in adult patients of different age groups
Author:
E.A. USHKALOVA1, S.K. ZYRYANOV1,2, O.I. BUTRANOVA1
1RUDN University, Moscow; 2City Clinical Hospital No. 24, Department of Healthcare of Moscow, Moscow
Summary:
To reduce the risk of developing adverse events (AEs) and increase the adherence of elderly patients to treatment, it is recommended to limit maximally the total number of prescribed drugs (DR), using one drug for the treatment of two or more pathologies if possible. The drugs that meet the criteria for use in elderly patients and / or patients with comorbidity include the original Russian drug Mexidol® (ethylmethylhydroxypyridine succinate), which has a multimodal mechanism of action and has multiple pharmacological effects. In order to study the safety of Mexidol in comparison with placebo in different age groups of patients with chronic cerebral ischemia, a post hoc analysis of the international multicenter, randomized, double-blind, placebo-controlled MEMO study with an adaptive design was carried out, which assessed the efficacy and safety of sequential therapy with Mexidol®, a solution for intravenous and intramuscular injection, 50 mg/ml (NPK PHARMASOFT, Russia) and Mexidol® FORTE 250 film-coated tablets, 250 mg (NPK PHARMASOFT, Russia) in patients with chronic cerebral ischemia. The study involved 318 patients aged from 40 to 90 years. Comparable safety and tolerability of Mexidol was demonstrated in middle-aged and elderly people with chronic cerebral ischemia, including patients over 75 years of age. Keywords: adult patients of different age groups; elderly; MEMO research; Mexidol®; Mexidol® FORTE 250; ethylmethylhydroxypyridine succinate; safety.
Hypoxia and oxidative stress in cerebral circulation insufficiency — effective ways of correction
Author:
E.I. CHUKANOVA, A.S. CHUKANOVA, D.M. RODIONOVA
Pirogov Russian National Research Medical University, Moscow, Russia
Summary:
Cerebrovascular diseases (CVDs) are one of the urgent problems of clinical neurology and the second most common cause of dementia. Vascular factors leading to the development of hypoxia, oxidative stress, mitochondrial, endothelial dysfunction and, ultimately, to the development of apoptosis with the formation of degenerative brain changes are considered among the main risk factors for the development of CVD. The most important mechanisms of the development of TFR are hypoxia and oxidative stress, which indicate the need for the use of drugs with antihypoxant and antioxidant activity. Such drugs include Mexidol (ethylmethylhydroxypyridine succinate). Mexidol directly affects the pathogenetic factors of the formation of ischemic-hypoxic brain damage, has a high clinical efficacy in the treatment of various forms of cerebral circulatory insufficiency. Keywords: chronic cerebrovascular insufficiency, hypoxia, oxidative stress, vascular cognitive impairment, endothelial dysfunction, Mexidol.
Efficacy of Mexidol in patients with type 2 diabetes mellitus with neurological complications
Author:
E.L. PUGACHEVA
Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
Summary:
Objective. Complications of Diabetes mellitus (DM), depends on the severity of hypoxic tissue damage. Amelioration of hypoxic injury may improve current therapy approaches and enhance the quality of life in patient’s cohort suffered from DM. Material and methods. 30 pts which DM were enrolled into the study. Mexidol forte, was given IV 500 mg/day for 14 days, follow up with oral administration 250 TID. Clinical impression, neuropsychological scales and biochemical blood tests were recorded. Results. Mexidol administration improved cognitive functions, decreased the level of asthenia, depressia, improved sleep disturbances, and normalized biochemical landscape. Conclusions. Mexidol administration for the period 75 days may serve as important therapeutic supplementation and considered as adjunctive therapy in the treatment of patients with DM. Keywords: Diabetes mellitus, hypoxia, oxidative stress, antioxidants, neurotransmitters, antihypoxive medications, Mexidol.
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.