Aim. To determine the value of different blood pressure (BP) measurement methods for arterial hypertension (HT) chronotherapy efficacy assessment. Material and methods. Two similar open, randomized, cross-over studies (morning vs evening intake) were carried out. Duration of the initial wash-out period was 2 weeks; duration of both treatment courses — 3 weeks; the interval between courses — 1 week. Only patients with stable HT (mean day-time BP>135/85 mm Hg) were included. Ambulatory BP monitoring (ABPM) was carried out prior to treatment and at the end of both treatment courses. The patients performed home BP monitoring (HBPM) throughout the study. Pharmacokinetics of verapamil (n=14, mean daily dose — 240.0±16.3 mg) was studied to assess compliance with verapamil therapy. In ramipril trial (n=30) its mean daily dose was 8.9±0.7 mg. The following main ABPM variables were analyzed: ABPM means and variability, maximal and minimal values, nocturnal BP fall, parameters of Fourier transformation and smoothness index. The morning and evening BP means and morning BP surge (morning – evening BP) were assessed by HBPM. Student’s t-value and Mahalanobis distance were used to evaluate individual value of each variable (“morning” vs “evening” effect). This analysis was first done separately for each trial. After that, combined data were analyzed. Results. Overall antihypertensive effect was more intense with morning ramipril (p<0.05) intake and evening verapamil intake. The t-values ranged 2.2-2.3 for nocturnal BP fall; 2.0-2.1 for night-time BP variability; 3.8-4.3 for morning BP surge. The t-values of office and 24-hour BP were low (0.2-1.7). Conclusion. Morning BP surge based on HBPM is a good instrument for chronotherapy effect assessment. Evening administration of antihypertensive drugs causes nocturnal BP fall shift towards “dipper” status.

Aim. To study therapeutic equivalence (efficacy, safety and tolerability) of original clopidogrel (Plavix) and its generic (Egitromb) in patients of high cardiovascular risk. Material and methods. Thirty one patients with coronary heart disease and indications for clopidogrel therapy were involved into the randomized cross-over blind study. Half of the patients received original clopidogrel (75 mg daily) during the first 2 weeks and then they received generic clopidogrel in the same dose during next 2 weeks. Another half of the patients received the drugs in reverse order. Antiplatelet activity of Plavix and Egitromb was estimated by effects on ADP-induced platelet aggregation initially and after 2 weeks of treatment with each drug. Study blinding was provided by the following approach: doctors of cardiology clinic performed clinical monitoring and drug distribution; coded blood samples for platelet aggregation assessment were studied in independent laboratory of thrombosis; statistical data analysis was performed by biostatistics expert in other research center. Results. 2-week therapy with each drug led to a significant decrease of ADP-induced platelet aggregation which remained low after switching from original drug to generic and vice versa. Aggregation dynamics did not depend on the first administered drug. There were no significant differences between aggregation changes as a result of treatment with original or generic drug. No one adverse event was observed in association with both drugs therapy. Conclusion. Generic drug Egitromb (Egis, Hungary) and original clopidogrel Plavix (Sanofi-Aventis, France) have equivalent antiplatelet effect.

Aim. To evaluate the changes of respiratory function in patients with rheumatic heart disease (RHD) complicated with pulmonary hypertension (PH) by the spirographic investigation. Materials and methods. Patients (n=56; 4 men and 52 women; aged 63,25±7,93) with rheumatic combined mitral and aortic valvular disease were examined. Medical history analysis, physical examination, general clinical investigation including ECG, chest X-ray, 2D-echocardiography and spirography were performed.  Results. 36% of the patients had normal pulmonary arterial systolic pressure (PASP) (<30 mm Hg), 48% had PH of degree I and 16% - PH of degree II. Restrictive changes of spirogram were found in 27% of patients: in 30% of patients with PH of degree I, in 44% of patients with PH of degree II and in 5% of patients with no PH. Bronchoobstruction was detected in no one patient. Pulmonary restriction significantly (p<0,05) correlated with PH, but no significant difference was found between groups with PH of I and II degree. No any association between PASP, spirogram changes and type of valvular lesion was revealed. Conclusion. Patients with RHD complicated with PH have pulmonary restrictive changes according to spirographic investigation.

Aim. To assess propafenone antiarrhythmic efficacy and optimal timing of the drug administration for relief of persistent atrial fibrillation (PAF). Material and methods. 24 patients (19 men, 5 women, aged 53,8±13,3) with PAF (duration is more than 7 days) were included in the study. PAF was confirmed clinically as well as by ECG and daily ECG monitoring. Indications for sinus rhythm recovery by propafenone were defined in according to the ACC/AHA/ESC recommendations (2006). 12-lead ECG was performed before the fist administration and 2, 4, 8, 12, 24 hours and some next days after propafenone therapy start. Echocardiography and thyroid hormone tests were also performed. Propafenone was administered additionally to standard treatment of the underlying disease and oral anticoagulants. The first dose of propafenone was 300 mg, after 4 hours patients received next dose of 300 mg if atrial fibrillation persisted and no side effects were observed, then doses of 300 mg were administered every 6-8 hours (but not more than 900-1200 mg per day) during 5 days. Maintenance propafenone dose of 450-600 mg daily was used in case of sinus rhythm recovery. Results. Sinus rhythm was restored in 41,6% of patients taking propafenone, and time of sinus rhythm recovery was 53,1±28,9 hours after therapy start. Propafenone antiarrhythmic efficacy in the loading dose (300 mg) was 4,2%. Propafenone efficacy during the first 24 hours (dose of 700±282,8 mg) was 12,5%. The maximum rate of sinus rhythm recovery was observed during the first 2-3 days of propafenone receiving (60% of all patients with rhythm recovery). Patients with unrecovered sinus rhythm had longer duration of PAF in comparison with this in effectively treated patients, 105,8±89,0 vs 39,7±38,9 days (p<0,05), respectively, as well as the more prominent basal pulse deficit, 24,6±15,0 vs 13,56±5,7 beats per minute (p<0,05), respectively. Cardiac and transient noncardiac side effects were registered in 8,6 and 4,3% of patients taking propafenone in dose of 900-1200 mg/day, respectively. Side effects did not require propafenone therapy cessation. Conclusion. Propafenone (900-1200 mg/day) antiarrhythmic efficacy in PAF was 41,6%. The probability of sinus rhythm recovery was maximal during the first 2-3 days. Ineffectively treated patients had longer duration of PAF last episode and more prominent basal pulse deficit in comparison with these in effectively treated patients. Transient side effects not requiring propafenone (900-1200 mg/day) withdrawal were observed in 12,6% of patients.

Aim. Тo compare the cost-effectiveness of antihypertensive therapy based on a generic and original drugs of amlodipine in patients with arterial hypertension (HT) degree 1-2 in NORST study. Material and methods. Patients (n=60) with HT degree 1-2 were involved in NORST study. After wash-out period they were randomized to receive generic (Group 1) or original (Group 2) amlodipine in the initial dose of 5 mg daily. In case of insufficient antihypertensive effect dose of amlodipine was increased to 10 mg per day and then successively lisinopril 10 mg daily and hydrochlorothiazide 12.5 mg one time per day were added. The total duration of treatment was 10 weeks (70 days). Achieving target blood pressure (BP) (<140/90 mm Hg) was the criterion of the effectiveness of therapy. Cost-effectiveness analysis of treatments in all patients was performed after individual analysis of the target BP achieving. Results. The target BP level was achieved in 25 (89%) patients of Group 1 and in 27 (96%) patients of Group 2. Total direct costs over 10 weeks amounted to 21 206 rubles in group 1, and 80 073 rubles in group 2. The cost-effectiveness ratio (CER) for group 1 was: CER=21 206/0.89=23 827 rubles. For Group 2, CER=80 073/0.96=83 409 rubles. Costs for achieving target BP in 1 patient of Group 1 were 3,5 times lower than these in group 2. Conclusion. The use of generic amlodipine (Stamlo M) has opportunity to draw in the healing process more hypertensive patients due to reducing the cost of treatment.

Pulmonary thromboembolism (PTE) — a life-threatening condition that can lead to death at any age. PTE — is not an independent disease, but it is a complication of venous thromboembolism. Conflicting opinions about the possibility of using tissue plasminogen activator (tenekteplase) expressed in the literature. Clinical case of the tenekteplase use in 42 years old woman with acute massive PTE and its results are described. PTE in the case was observed simultaneously with diabetic ketoacidosis. Full resolution of this thrombus according to computer pulmonary angiography was observed in patient hospitalized within 24 hours after symptom onset. This is one of the first cases of effective application of the tenekteplase in patients with massive PTE and diabetic ketoacidosis.

Clinical cases of long-term use of rosuvastatin are presented with an estimation of its effect on the soft end (lipid profile) and hard end (number of heart attacks, strokes, heart failure, hospitalization for cardiovascular causes) points are given. The results of studies on rosuvastatin (ASTEROID, CORONA, METEOR, ORION, COSMOS) are presented. Clinical guidelines on the management of patients with stable ischemic heart disease are considered on the example of COURAGE trial.

Diagnosis and treatment of atrial flutter (AF) is an important clinical task. Epidemiological data, electrophysiological mechanisms and updated classification of AF are presented as well as treatment algorithm that is suggested by leading experts. Two strategies of AF therapy are shown: "rhythm control" and "rate control". Author paid attention that ventricular rate reduction in AF is more difficult task than this in atrial fibrillation. Indications for different AF treatments are discussed: pharmacotherapy, pacing and cardioversion as well as surgical methods.

Contemporary scientific and practical data about various lipid metabolism disorders (dyslipidemia) in children are discussed. Spectra lipids, phospholipids and lipoproteins in blood serum and erythrocyte membranes are presented. Characteristics of dyslipidemia and hypolipidemia, classification of hyperlipidemia, a description of acetonemic vomiting syndrome are given. Basic principles of dyslipidemia treatment as well as therapy of obesity associated with dyslipidemia are described.

A role of angiotensin-converting enzyme (ACE) inhibitors in cardiovascular diseases treatment and prevention is discussed. Some large randomized clinical trials are analyzed. Physical and chemical properties of drugs and its evidence base are considered among possible factors of ACE inhibitors choice. A problem of ACE inhibitor choice is also discussed in context of secondary prevention of cardiovascular complications in arterial hypertension and after myocardial infarction. It is concluded that the choice of any drug for cardiovascular disease treatment is mainly determined by its evidence base.

New data and perspectives of antithrombotic therapy are highlighted in patients with atrial fibrillation. Factors of warfarin therapy efficacy, as well as the possibility of new antithrombotic drugs are considered. Special attention are paid to the direct thrombin inhibitors — dabigatran. Possibilities and usage prospects of dabigatran in patients with atrial fibrillation are discussed in detail in the light of new results of RE-LY trial.

Antiplatelet agents are a necessary component of modern atherosclerosis therapy. The difficulties of antiplatelet treatment lie in the balance between the necessary therapeutic effect of the drug and the risk of excessive action leading to the bleeding. Possibility to control pharmacodynamics effects of antiplatelet agents is still very limited. Pharmacology of antiplatelet drugs is growing rapidly. Some of new antiplatelet drugs are on their way to clinical application — prasugrel, ticagrelor, elinogrel, inhibitors of thromboxane and thrombin receptors. Clinical pharmacology of these drugs is different. This requires a doctor's good knowledge of their identity to avoid the development of iatrogenic complications.

Current issues of atherothrombosis prevention and treatment optimization with antiplatelet therapy in patients with cardioascular diseases are discussed. Role of clopidogrel in contemporary antiplatelet therapy is focused on, especially in the aspect of the problem of aspirin resistance. Chronology of the clopidogrel generics appearance and prospects of their use is presented.