Effects of dipyridamole and its use in neurology

Dipyridamole has been on the pharmaceutical market since 1959 and, as a pyrimidyl-pyrimidine compound, has a variety of mechanisms of action. The very first action of dipyridamole was its antianginal effect. In subsequent years, attention was drawn to the antiplatelet properties of dipyridamole, which are related to inhibition of platelet phosphodiesterase as well as to blocking adenosine transport. Another important property of dipyridamole is its effect on the deformability of red blood cells, thereby improving microcirculation. Dipyridamole affects changes in the dynamics of platelet activity and vascular reactivity and causes improvement of cerebral perfusion. Due to its pronounced antiplatelet properties, the drug has been widely studied for the prevention of ischemic strokes and transient ischemic attacks, both as monotherapy and in combination with other drugs. Unlike other platelet antiaggregants, dipyridamole does not have a damaging effect on mucous membranes. Its antiplatelet effect is not accompanied with inhibition of cyclooxygenase activity and reduction of prostacyclin synthesis. In the treatment of cerebral circulation disorders, dipyridamole can be used to control the antithrombotic effect by selecting the optimal dose of the drug. Dipyridamole has antioxidant properties, enhances NO-mediated pathways, has indirect anti-inflammatory effects via adenosine and prostaglandin-2 as well as direct anti-inflammatory effects and several other effects. Dipyridamole is considered a safe drug based on decades of clinical experience. Its side effects are usually limited and transient. Given the diverse effects of dipyridamole, it can be used for a wide range of pathologies other than thrombosis prevention. Data on the efficacy and safety of dipyridamole in various diseases of the neurological spectrum are presented.

P427Influence of ranolazine on cardioversion rate in patients with new onset atrial fibrillation and ischemic disease of the heart

Background Ranolazine is a piperazine derivative, mainly used as antianginal drug in patients with ischemic disease of the heart (IDH). Despite its antianginal effect, it has an antiarrhythmic effect by inhibiting of late sodium and rapid potassium rectifier current. Aim of the study was to assess the additional antiarrhythmic efficacy of ranolazine in patients with new onset atrial fibrillation (AF) and IDH. Material and Methods 168 eligible patients with IDH and short duration of new onset AF were enrolled in this study. Among them, 92 were treated additionally ranolazine to the standart therapy – Group I while 76 only with standart therapy – Group II. The choice of antiarrhythmic drug for cardioversion was either amiodarone or propafenone at the discretion of the doctor. Primary endpoint was recovering of sinus rhythm. All statistical analysis were performed using student t-test. Results Mean age of patients was 66 ± 11.5 years, male 48% in ranolazine group (Group I) and 64.5 ± 12.0 years, male 46% in Group II, and there were no statistically significant differences between two groups. Both groups of patients were characterized by median AF episode duration of 12 (4; 24) hours. Amiadoron was administered in 70 % (n = 65) of patients in Group I and in 77% (n = 59); propafenon in 30% (n = 17) of patients in Group I and 23% (n = 17) in Group II. Cardioversion rate was significantly higher in Group I than Group II (87% vs. 74%, P < 0.05;). There were not observed safety endpoints in Group I whereas 3 safety endpoints (severe bradycardia and arterial hypotension) were observed in Group II (P > 0.05). Conclusion Adding ranolazine to the standard therapy in patients with IDH seems to have a beneficial role in restoring sinus rhythm in recent new onset AF.

Evaluation of the antianginal effectiveness of trimetazidine in a new dosage form for a single dose, depending on the region of the Russian Federation. ODA trial results

The goal evaluation of the effectiveness of treatment with the new TMZ OD dosage form in different regions of the Russian Federation and regional differences in the clinical characteristics of patients with coronary artery disease included in the observation, the nature of their therapy, the presence and degree of correction of modifiable risk factors in real clinical practice. Material. Used database research ODA (Evaluation of the effectiveness and therapeutic response to Preductal OD 80 mg in everyday practical use for the treatment of stable angina), which was conducted in 56 cities of the Russian Federation. The analysis was carried out in the Central, North-West, Volga districts and regions united by the territorial principle – Southern + North Caucasian + Crimea + Sevastopol and Ural + Siberian + Far Eastern. Results. By region, there were no differences in the ratio of men and women included in the observation, the number of smoking patients (about 15%), overweight (about 80% of patients), arterial hypertension (exceeding 85%),dyslipidemia (over 90%), and atrial fibrillation (met at each 8-10 included patient). The proportion of patients older than 65 years was greater in the Central, North-West and Ural regions. Unfavorable heredity in coronary artery disease is more common in the Southern, Central and Ural regions. More than 2/3 of the patients had low physical activity, and in the South — their number reached ¾ of all included in the observation. The largest number of patients with diabetes was in the Central and North-West regions (every fourth patient), in the Ural region every fifth. The lowest frequency of statin prescribing was in the Volga region. The smallest number of those receiving RAS inhibitors was in the North-West, Ural and South regions. Beta blockers took more than 80% of patients. Only 35% of patients had a target systolic blood pressure. The smallest proportion of people with target blood pressure values was in the NorthWest and South regions. Adding TMZ OD to therapy or replacing previous therapy with trimetazidine on TMZ OD in all regions resulted in a significant (p <0.001) decrease in the incidence of angina attacks by as early as 1 month of therapy and the antianginal effect increased by the third month of treatment. By the third month of treatment, the average frequency of angina attacks was the lowest in the North-Western and Ural regions (significantly lower than even in the Central region) and remained higher only in the Volga region compared to the Central, North-Western and Ural regions. During follow-up, treatment compliance increased significantly in all regions. Conclusion. The fight against major risk factors remains insufficient and efforts should be made to change the situation in all regions of the Russian Federation. The inclusion of trimetazidine in therapy in the new TMZ OD dosage form allows to obtain a pronounced antianginal effect and increase adherence to therapy. Low adherence can be overcome by careful observation and closer contact between doctors and patients.

Cliniko-experimental research of trimetazidine efficiency at the myocardium ischemia

The randomized controllable clinical research of Trimetazidine (Preductal MB) efficiency was spent at 95 patients with a stable angina pectoris. There were revealed the authentic increase in 2 times of treatment’s clinical efficiency in patients, who in addition to basic therapy appointed Trimetazidine for the account of more expressed antianginal effect and increase of physical working capacity. Additional appointment of Trimetazidine at a myocardium ischemia promoted the reduction of energy deficiency and tissue hypoxia. Last position has proved to be true according to experimental data: at rats males of line Vistar at experimental IHD the introduction of Trimetazidine led to increase of recycling of carbohydrates with the power purposes in a cardiac muscle that was accompanied by signs of stabilisation of cardiomyocytes’ membranes and reduction of degree of tissue hypoxia.

Efficiency of antioxidant therapy in patients with acute myocardial infarction and unstable stenocardia

The efficiency of preductal (trimetazidin), essentiale, li postabil and vitamin E in acute myocardial infarction and unstable stenocardia is estimated. It is shown that in unstable stenocardia and in the acute period of myocardial infarction the high level of lipid peroxide oxidation and the decrease of erythrocyte stability are observed. The clinical efficiency of antioxidants in the treatment of the acute forms of ischemic heart disease is proved: the antianginal effect is achieved, readaptation possibilities of patients to physical loads are increased, effect of anti rhythmical drugs is intensified, myocardial infarction size is limited (especially in using preductal). The presence of pronounced antioxidant and membranoprotective properties in preductal, lipostabil, essentiale comparing well with -tokopherol is proved. It is shown that preductal manifests the antianginal effect by the microcirculation system and metabolism correction. Antioxidants promote the decrease of blood elements sledge and increase of the number of perfused capillars.