Pharmacoeconomic analysis of the neuroprotective medicines in the treatment of ischemic stroke
Author:
R.I. YAGUDINA1, A.YU. KULIKOV1, V.A. KRYLOV1, E.YU. SOLOVIEVA2, A.I. FEDIN2
1Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia;
2Pirogov Russian National Research Medical University N.I.Pirogov Russian National Research Medical University of the Ministry of Health
of Russia, Moscow, Russia
Summary:
Objective. To perform a pharmacoeconomic analysis of the most frequently prescribed neuroprotective medicines for treating patients with mild ischemic stroke in the acute and early rehabilitation periods in the Russian Federation. Material and methods. Three medical technologies were compared: ethylmethylhydroxypyridine succinate (mexidol), inosine + nicotinamide + riboflavin + succinic acid (cytoflavin) and a deproteinized hemoderivate of the blood of calves (actovegin). Cost minimization analysis, budget impact analysis and sensitivity analysis were performed based on the indirect comparison results. Results. Efficacy analysis shows that mentioned above medicines have the same efficacy: mean difference mexidol is 0,2 (CI min 0,25; max 0,65), cytoflavin — 0,61 (CI min 0,23; max 0,99), actovegin 0,2 (CI min 0,18; max 0,22). The cost minimization analysis for the Russian Federation shows that mexidol therapy is associated with the lowest costs, while savings are observed both in the evaluation of total costs and separate components: intravenous ampoules and tablet forms. The savings in comparison with cytoflavin and actovegin are 231 RUB and 12,872 RUB, respectively. These savings will be enough to treat five patients with ischemic stroke (IS) with mexidol. Moreover, oral mexidol therapy is cheaper than the same dosage forms of cytoflavin and actovegin by 481 RUB and 3,164 RUB, respectively. This is an advantage for the treatment of population at the outpatient stage. Budget impact analysis has shown that the budget for the medicines for treating IS at the current distribution between treatment regimens, is estimated at 1.99 BN RUB. The increase in the proportion of patients receiving mexidol by 10% reduces total costs to 1.75 BN RUB, which is 240 M RUB less than current costs. With these savings 85 thousand patients with IS could be treated. The sensitivity analysis reveals that the result of the cost minimization analysis and the budget impact analysis remain stable when both the amount of the population and the cost of 1 mg of mexidol vary from –10% to + 10%. Conclusions. Mexidol has the same efficacy as alternatives. However mexidol is superior to cytoflavin and actovegin in terms of cost minimization analysis. The savings from one course of alternatives will cover costs of treatment of five patients with IS using mexidol. The increase in the proportion of patients receiving mexidol is associated with savings, which allows us to consider mexidol therapy of mild IS as budget-saving in the Russian Federation. Keywords: pharmacoeconomics, indirect comparison, cost minimization analysis, budget impact analysis, neuroprotectors, ischemic stroke.
Evaluation of blood rheology by patients with acute ischemic stroke with Mexidol administration
Author:
D.M. PLOTNIKOV1, M.N. STEGMEIER1, O.I. ALIEV2
1 Department of Neurology and Neurosurgery, Siberian State Medical University, Tomsk, Russia;
2 Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
Summary:
Objective. To study rheological properties of blood in patients with acute ischemic stroke treated with mexidol. Material and methods. Sixty patients with acute stroke, including 32 patients who received mexidol (500 mg/IV/20 days) and 28 people who received magnesium sulfate (2000 mg/IV/20 days) were examined. The control group included 20 people without a cardiovascular pathology. Blood rheology (viscosity of whole blood, plasma viscosity, hematocrit, aggregation and deformability of erythrocytes, fibrinogen level) was evaluated in patients three times: for the first 12 hours, 3—5 days and 18—20 days after hospitalization. Results. Hyperviscosity syndrome was observed in all patients with stroke. A significant decrease in blood viscosity was found in patients treated with mexidol: in the 3–5th day at low shear rates and in the 18—20th day at 3—100 s–1 shear rates. Significant differences in hematocrit (p=0.026) and fibrinogen levels (p=0.017) in patients treated with different drugs were found in the 18—20th day of the disease. Higher erythrocyte deformability index was recorded in patients treated with mexidol in the 3—5th day at shear rates of 90 and 890 s–1, in the 18—20th day at shear rates of 90—360 s–1. Conclusion. The study confirms the impact of mexidol on the fluidity of blood during the acute cerebral ischemia and shows its efficacy in reducing blood viscosity, decreasing the level of hematocrit and fibrinogen, increasing the deformability of erythrocytes.
Keywords: acute ischemic stroke, rheological parameters of blood, blood viscosity, erythrocytes deformability, mexidol (ethylmethylhydroxypyridine succinate), treatment of stroke.
Effect of mexidol on the efficiency of intravenous thrombolytic therapy for ischemic stroke during the therapeutic window
Author:
Knni K.S., Dyomin T.V., Adeeva L.B.
Interregional Clinical and Diagnostic Center, Kazan, Russia 12A, Karbyshev St., Kazan, Republic of Tatarstan 420101
Summary:
Objective: to evaluate the effect of intravenous mexidol on the efficiency of intravenous thrombolytic therapy (TLT) during the therapeutic window. Patients and methods. The retrospective study enrolled 123 patients with ischemic stroke (IS) who had undergone intravenous TLT in the vascular centers of the Republic of Tatarstan. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the time course of changes in their neurological status. According to the baseline severity of a neurological deficit, all the patients were divided into three subgroups: 1) mild IS (<8 NIHSS scores at admission); 2) moderate IS (>8 scores); and 3) severe IS (<16 scores). All the patients underwent X-ray computed tomography at admission, at 24 hours after TLT, and in case of worsening of their health status. Results. The prehospital use of mexidol followed by TLT in patients with IS had a positive effect on the regression of neurological deficit regardless of the severity of the disease. There were significant differences in the degree of regression of neurological deficit according to NIHSS at 24 hours and 10 days after hospital admission in patients with severe IS, who received intravenous mexidol at the prehospital stage and who did not take this drug before TLT. The pre-TLT use of mexidol contributed to higher regression of neurological deficit. There was a lower frequency of hemorrhagic transformations in the patients who used mexidol at the prehospital stage versus those who did not. Conclusion. The findings demonstrate the positive effect of mexidol on the efficiency and safety of TLT in patients with IS.
Keywords: ethylmethylhydroxypyridine succinate; intravenous thrombolytic therapy; ischemic stroke; neuroprotective therapy.
Assessment of the efficacy of mexidol in the combination with hyperbaric oxygen in acute ischemic stroke
Author:
N.S. KULAI, E.YU. KOVALCHUK.
Saint-Petersburg I.I. Dzhanelidze research institute of emergency medicine, Saint-Petersburg, Russia.
Summary:
Objective. To study the efficacy of mexidol in the combination with hyperbaric oxygenation (HBO) in comparison with the standard HBO sessions in patients with acute ischemic stroke. Material and methods. One hundred and twelve patients were examined. In the main group, 48 patients underwent HBO and received treatment with mexidol. The control group consisted of 64 people who underwent the standard HBO sessions only. Results and conclusion. The use of combination therapy (HBO+mexidol) leads to the significantly more rapid normalization of acute phase indices which are correlated with neurological deficit reduction.
Keywords: ischemic stroke, hyperbaric oxygen therapy, mexidol.
An influence of submaximal (submineximal) doses of mexidol on oxidant stress and inflammation in the acute period of ischemic stroke
Author:
A.R. GODUNOVA, A.A. RAKHIMOVA, O.I. LEONTYEVA, I.G. TALIPOVA, R.M. YAKHIN, SH.G. MUSIN.
Emergency Hospital, Naberezhnye Chelny, Russia.
Summary:
Objective. To study an effect of submaximal doses of mexidol on the dynamics of biochemical markers of inflammation and damage to brain tissue in the acute period of ischemic stroke. Material and methods. A total of 60 patients admitted in the first 6h after disease onset with a verified ischemic stroke (7-9 points on the ASPECT scale) were enrolled in the study. Thirty patients in the study group received submaximal doses of mexidol: 750 mg infusion dropwise in 250 ml of 0.9% NaCl solution for 6 days. Thirty patients of the control group received standard therapy. Biomarkers and neurological status were evaluated within 60 minutes from the time of admission to the hospital and after 6 days. Results and conclusion. In both groups, the changes in CRP, IL-6, and fibrinogen did not contribute to the efficacy of mexidol. The brain natriuretic peptide (BNP) biomarker, plasma-A-associated pregnancy (PAPP-A) biomarker, average NIHSS score and mean cerebroasthenia score on the MFI-20 scale in the study group were significantly reduced compared to the control group. This study indicates a decrease in oxidative stress and signs of inflammation, a reduction of the severity of neurological deficit and an increase in physical activity of patients treated with submaximal doses of mexidol. Given the activation time of the damaged antioxidant system of the body, the recommended period of treatment is 3 months.
Keywords: antioxidant stress, inflammation, acute period, ischemic stroke, mexidol.
Modern strategies of protection of hypoxic-ischemic brain damage
Author:
S.N. YANISHEVSKY, N.V. TSYGAN, S.YU. GOLOKHVASTOV, R.V. ANDREEV, I.V. LITVINENKO, O.S. KARPOVA, V.A. YAKOVLEVA.
Kirov Military Medical Academy, St. Petersburg, Russia.
Summary:
Nowadays, there are two complementary approaches to treatment of patients with ischemic stroke: reperfusion and neuroprotection. The main purpose of neuroprotection is to intervene ischemic cascade at every stage of the pathological process and thus avoid the death of nerve cells and expand the therapeutic window for reperfusion therapy. The use of drugs with neurotrophic, antioxidant and neuroregenerative effects is pathogenically explained at all stages of post stroke rehabilitation. Ethylmethylhydroxypyridine succinate (mexidol) is a derivative of succinic acid with antihypoxic, membrane protective, nootropic, anticonvulsant and sedative action. The majority of researchers confirmed the positive effect of mexidol expressed as the marked regression of neurological deficit and wider opportunities for further early rehabilitation. The results of the randomized double blind multicenter placebo-controlled, parallel-group trial of the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (EPICA) were published in 2017. The results of the study showed the best positive dynamics of neurological function recovery in case of timely treatment with mexidol with the following two month therapy. The safety of the long-term use of mexidol was confirmed.
Keywords: stroke, acute period, neuroprotection, succinate, efficacy of treatment, safety of therapy.
Results of a randomized double blind multicenter placebo-controlled, in parallel groups trial of the efficacy and safety of prolonged sequential therapy with mexidol in the acute and early recovery stages of hemispheric ischemic stroke (EPICA)
Author:
L.V. STAKHOVSKAYA, N.A. SHAMALOV, D.R. KHASANOVA, E.V. MELNIKOVA, A.S. AGAFIINA, K.V. GOLIKOV, E.I. BOGDANOV, A.A. YAKUPOVA, L.V. ROSHKOVSKAYA, L.V. LUKINYKH, T.M. LOKSHTANOVA, I.E. POVERENNOVA, L.A. SHEPANKEVICH.
Pirogov Russian National Research Medical University, Moscow, Russia; Research Institute of Cerebrovascular Pathology and Stroke of Pirogov Russian National Research Medical University, Moscow, Russia; Interregional Clinical-Diagnostic Center, Kazan, Russia; City Hospital №26, St. Petersburg, Russia; City Hospital №40, St. Petersburg, Russia; City General Hospital №2, St. Petersburg, Russia; Kazan State Medical University, Kazan, Russia; Nikolaev Hospital, St. Petersburg, Russia; Vsevolga Clinical Interregional Hospital, Leningrad Region, Russia; Pirogov City Clinical Hospital №1, Samara, Russia; Seredavin Samara Regional Clinical Hospital, Samara, Russia; Research Institute Experimental and Clinical Medicine, Novosibirsk, 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). Material and methods. A randomized double blind multicenter placebo-controlled, in parallel groups trial included 151 patients (62 men and 89 women) with hemispheric IS. Using a method of simple randomization, 150 patients (62 men and 88 women), aged 40-79 years, were randomized into two groups. Patients of Group I were treated with mexidol: 500 mg/day IV infusion for 10 days, followed by 125 mg tid (375 mg/day) PO for 8 weeks. Patients of Group II received the placebo according to the same scheme. The total duration of patients’ participation in trial ranged from 67 to 71 days. Results. By the end of treatment, the mean score on the modified Rankin scale (mRS) was lower in Group I compared to Group II (p=0.04). In Group I, the decrease in mRS mean score (Visit 1-5) was more prominent (p=0.023), percentage of patients with 0-2 scores by mRS scale (Visit 5) was higher (p=0.039), mean NIHSS score lower (p=0.035) in Visit 5 compared to group II. By the end of treatment, the decrease in mean NIHSS score in patients with diabetes mellitus was more prominent in Group I in comparison with Group II (p=0.038). In Group I, the dynamic of improvement of quality of life was more prominent and started from Visit 2 in general population and subpopulation of patients with diabetes mellitus. The share of patients with no problems with movement in space was higher in Group I (p=0.022). There were no statistically significant differences in frequency of side effects in patients of both groups. Conclusion. It is recommended to include mexidol in therapy of patients with IS in the acute and early rehabilitation stages.
Keywords: acute disturbances of cerebral circulation, mexidol, ethylmethylhydroxypyridine succinate, efficacy and safety, ischemic stroke, acute period, acute rehabilitation period, EPICA.
Contemporary paradigm of rational stroke treatment
Author:
S.A. ZHIVOLUPOV, YU.S. BUTAKOVA, I.N. SAMARTSEV.
Department of nervous diseases of the Military Medical Academy; primary vascular compartment Novodvinsk City Hospital, Saint Petersburg, Russia.
Summary:
Stroke was and remains one of the world’s leading medical and social problems. Nowadays we are watching permanent sometimes cardinal changes in view about etiology, pathogenetic mechanisms and therapy of patients with stroke. In this work there have been elucidated contemporary theoretical and practical aspects of stroke treatment and prophylaxis based on the results of multicenter clinical trials and experience of leading foreign and native specialists. Much attention is devoted to the pharmacotherapy of patients with stroke. It is showed that application of neuroprotective drugs is of great importance, among which antihypoxants with pleiotropic action play a crucial role (mexidol).
Keywords: stroke, therapy, prophylaxis, neuroprotection, antihypoxants, mexidol.
Optimization of hypolipidemic therapy in patients with ischemic stroke and diabetes mellitus
Author:
L.A. SHCHEPANKEVICH, YU.A. NIKOLAEV, N.A. DOLGOVA.
Research Institute of Experimental and Clinical Medicine, Novosibirsk.
Summary:
Objectives. Evaluation of effectiveness of Mexidol in optimization of hypolipidemic therapy in ischemic stroke and diabetes mellitus patients. Material and methods. Authors analyzed the indicators of lipid status: total cholesterol, low-density lipoproteins, high density lipoproteins, triglycerides and concentration of platelet factor-4, β-tromboglobulin, von Willebrand factor in 68 patients with acute ischemic stroke and diabetes mellitus. Authors investigate the dynamics of these parameters (1st, 21st, 3-d and 6th month after onset stroke) depending on timing and dose of Mexidol. Results. Long time therapy of Mexidol may optimize of hypolipidemic therapy in ischemic stroke and diabetes mellitus patients.
Keywords: ischemic stroke, diabetes mellitus, comorbidity, lipids, hemostasis, mexidol.
Neurometabolic therapy in secondary prevention of stroke
Author:
V.V. KOVALCHUCK.
Semashko City Hospital №38, St. Petersburg.
Summary:
Objective. To study the efficacy of mexidol in secondary prevention of stroke. Material and methods: We analyzed 3400 patients with stroke which were stratified into 7 groups: patients with cryptogenic ischemic stroke (II), arterial hypertension, atrial fibrillation, metabolic syndrome, syndrome of sleep-induced obstructive apnea/hypnea, diabetes mellitus, vasculitis. The assessment of efficacy was based on the absence of repeated II within 5 years of therapy. Results. Mexidol reduced the frequency of repeated II both in patients without concomitant diseases and in those with arterial hypertension, syndrome of sleep-induced obstructive apnea/hypnea, vasculitis, diabetes mellitus, atrial fibrillation and metabolic syndrome. Conclusion. The reliable efficacy of mexidol in secondary prevention of stroke was found out.
Keywords: stroke, secondary prevention, mexidol.