Background. Vitamins В6 В12 and folic acid (FA) therapy to reduce cardiovascular risk appears to be unreasonable. Negative results of recent large-scale trials might be due to high daily doses of the vitamins and widespread FA fortification programmes. Russian population is known to have high prevalence of FA and vitamin B12 deficiency. Aim. To evaluate the effect of FA, B6 and B12 vitamins (in doses approximate to daily maintenance) on long-term prognosis after elective percutaneous coronary intervention (PCI) in stable ischemic heart disease patients. Material and methods. 264 patients (213 male, age 58.8±1.0 years) after successful PCI were involved into the trial. Patients with clinical signs of the vitamins deficiency were not included. Patients were randomly assigned to receive combination of FA (0.6 mg/day), B12 (10 μg/day), and B6 (4 mg/day) vitamins along with the conventional therapy (n=97) or the conventional therapy only (n=167) for 20 months. The groups were comparable in age, gender and prevalence of coronary risk factors. Composite endpoint was defined as cardiovascular death, acute coronary syndrome, stroke or transient is- chemic attack and need for coronary/carotid revascularization. Results. The vitamins prescription to all of the patients did not reduce composite endpoint incidence according to multivariable regression analysis (RR 0,7; 95%CI 0,4-1,4; p=0,3). Subgroup analysis showed significantly lower composite endpoint incidence in patients who received vitamins and had initially low B12 blood level (<260 pg/ml) as compared to the control group (RR 0.09; 95%CI 0.01-0.9; p=0.04). Conclusion. Treatment with FA, B and B vitamins improves prognosis after PCI in patients with initially low blood vitamin B level.

Aim. To study influence of ivabradine as compared with bisoprolol on clinical and hemodynamic indices, exercise tolerance, endothelial function, quality of life (QL) and erectile function in patients with ischemic heart disease. Material and methods. 60 males with stable angina pectoris were enrolled into comparative randomized crossover open study. One half of patients randomly received ivabradine during 14 days with replace it with bisoprolol for the next 3 months, another half of patients received compared drugs in the reverse order . Treadmill-test and flow-mediated dilatation (FMD) test were performed initially and after 14 days of treatment with each drug. QL and erectile function were evaluated after 3 months with Seattle Angina Questionnaire (SAQ) and International Index of Erectile Function (IIEF-5), respectively. Results. Heart rate reduced by 16.7±4.6 (p<0.005) and 16.4±4.8 bpm (p<0.005) after 2 weeks of treatment with bisoprolol and ivabradine, respectively. 30 (50.0%) and 31 (51.7%) patients treated with bisoprolol and ivabradine, respectively , increased exercise tolerance ≥1 min in the treadmill-test. Ivabradine treatment, in comparison with bisoprolol one, was associated by more expressed increase in chronotropic reserve in treadmill-test (p<0.05) and significant improvement of sensitivity coefficient of brachial artery to tension shift in FMD (p<0.005). In patients with endothelial dysfunction bisoprolol (69.4 %) and ivabradine (52.8%) efficacy did not differ significantly. At the same time in patients with normal endothelial functions increase in exercise tolerance ≥1 min in treadmill-test was observed in 50% (p<0.05) and 20.8% of patients treated with ivabradine and bisoprolol, respectively. Both drugs significantly increased QL, and ivabradine improved erectile function (p<0.005) in comparison with bisoprolol. Conclusion. The If-channel inhibitor ivabradine and beta-blocker bisoprolol have a similar antianginal efficacy in patients with stable angina pectoris. Treatment with ivabradine, in comparison with bisoprolol, was associated with improvement of chronotropic reserve in treadmill-test (p<0.05), sensitivity coefficient of brachial artery to tension shift in FMD test (p<0.005) and erectile function (p<0.005).

Aim. To evaluate by modelling the economic benefits of left ventricular hypertrophy (LVH) regression in patients with arterial hypertension (HT) due to therapy with fixed combination of valsartan/amlodipine.  Material and methods. 20 patients (15 females and 5 males, aged 18 to 70 years) with essential HT accompanied by metabolic syndrome with a history of previous ineffective antihypertensive therapy were included into the study. All patients were treated with fixed combination of amlodipine/valsartan in doses of 5/160 and 10/160 mg depending on blood pressure (BP) level. Treatment duration was 24 weeks. Changes in BP level, LVH regression were assessed. Economic evaluation was performed on the basis of modelling with the specialized software Decision Tree 4.xla. Results. Effect of fixed amlodipine/valsartan combination therapy on LVH was used to estimate treatment effectiveness and to build the model. Patients were distributed according to left ventricular (LV) mass (at baseline and after 24 weeks of therapy). Significant decrease in LV mass from 205.8±50.4 to 181.9±45.1 g (p<0.05) was revealed. The model took into account economic and frequency factors for 10 year prognosis: this therapy prevents 36 deaths, 6 strokes, 24 myocardial infarction per 1000 patients. Absence of need in treatment of these prevented events can save 2 516 772.42 RUR for every 1 000 patients. It would reduce the total costs per patient during 10 years. Conclusion. Treatment with amlodipine/valsartan single pill combination has not only clinical advantages, but also pharmacoeconomic benefits. This combination reduces risk of acute myocardial infarction and death more effectively. Treatment with fixed valsartan/amlodipine combination saves maximum years of life with less cost during 10 years. Despite of higher pharmacotherapy costs, fixed valsartan/amlodipine combination reduces total costs due to prevention of fatal and nonfatal cardiovascular events.

Aim. To compare the efficacy and safety of urapidil (i/v solution 5 mg/ml in 5 and 10 ml ampoules) and enalaprilat (i/v solution 1.25 mg/ml in 1 ml ampoules) in the treatment of complicated hypertensive crises in patients with arterial hypertension, 1-3 degrees. Material and methods. Patients with complicated hypertensive crisis (n=70) were included into the comparative randomized study. Patients were randomized for treatment with urapidil (the initial dose 12.5 mg; if there was no effect after 15 minutes it was possible to re-infused urapidil 12.5 mg) or enalaprilat (the initial dose 1.25 mg). The frequency of target blood pressure (BP) achievement, BP and heart rate dynamics, as well as safety of treatment were evaluated in groups during 6 hours. Results. The frequency of target BP achievement in the urapidil treatment group was higher than this in enalaprilat group (96.7 vs 73.3%; p<0.001), for the first hour systolic BP (SBP) in the urapidil group reduced from 210.5±13.6 to 157.8±8.3 mmHg (p<0.05), and diastolic BP (DBP) - from 115.7±8.5 to 86.9±9.1 mmHg (p<0.05). In the enalaprilat group in the first hour SBP reduced from 208.1 to 182.5 mmHg (p<0.05), DBP — from 114.8 to 95.0 mmHg (p<0.05). During next 6 hours the urapidil group demonstrated longer lasting antihypertensive effect in comparison with enalaprilat. Both drugs did not have a significant effect on heart rate and showed no significant adverse events. In next 72 hours no one acute vascular event was registered in the patients of both groups. Conclusion. Urapidil is an effective and safe drug for arresting of complicated hypertensive crises. Its efficacy is not inferior to this of enalaprilat.

Aim. To compare the efficacy and safety of the slow-release isosorbide-5-mononitrate and of the nebivolol in patients with stable angina. Material and Methods. Patients (n=19) with ischemic heart disease (stable angina) were enrolled into randomized, double-blind, placebo-controlled, crossover study. They alternatively received nebivolol 5 mg QD or slow-release isosorbide-5-mononitrate 50 mg QD. The drug efficacy was assessed by changes in symptoms, angina attack number , sublingual nitroglycerin need, and treadmill test duration. Results. Patients treated with isosorbide-5-mononitrate shown significant increase in heart rate (HR) at rest in all time check-points in comparison with patients receiving placebo. HR significantly decreased 2 hours after nebivolol intake both single one and after 30 days of treatment (p<0.001). Duration of treadmill exercise significantly increased (vs placebo) 2 hours after a single intake of both isosorbide-5-mononitrate (454.3±37.1 vs 310.6±13.3 s; p <0.001) and nebivolol (428.6±33.3 vs 310.6±13.3 s; p<0.01). In one month of treatment isosorbide- 5-mononitrate and nebivolol reduced a number of angina episodes vs placebo (5.6±2.1 and 4.3±1.4, respectively , vs 8.6±2.4 episodes per month; p<0.05), the need for nitroglycerin (5.5±2.6 and 3.1±1.2, respectively , vs 6.7±2.2 sublingual tablets/month; p>0.05). No significant differences of these indicators were found between studied drugs. Conclusion. Nebivolol 5 mg daily is not inferior to slow-release isosorbide-5-mononitrate 50 mg daily in antianginal efficacy , significantly reduces HR, and much less causes headache and other side effects.

Aim. To analyze the structure of expenses associated with warfarin dose adjustment and international normalized ratio (INR) control for patients with atrial fibrillation (AF) per 1 year of treatment. Material and methods. AF prevalence rate was calculated according to the large population studies data. The study was performed based on methodology for Cost of Illness evaluation. Expenses associated with INR monitoring within the obligatory medical insurance program were calculated based on the general tariff agreement for 2011 year for one of the territorial subject of Russia. Expenses associated with INR monitoring in outpatient departments of university clinics and commercial laboratories were calculated based on price list of respective institutes. Expenses associated with INR monitoring in case of self-monitoring were calculated based on expenses for portable coagulometer and test strips purchasing.  Results. Around 539 000 people in Russia are needed warfarin therapy and associated continuous INR monitoring. In the obligatory medical insurance program the cost of warfarin is less than 1% of total costs and the direct costs of treatment and control of nearly 4 058.12 RUR/person per year , in university clinics, respectively , 0.03%, and 13 019.05 RUR, in case of self-monitoring - 0.01-0.05% and from 40 405.00 (in the first year) to7 404.98 RUR (in the consequent years), respectively. Conclusion. The cost of warfarin, regardless of the INR monitoring approach is less than 1% of the total cost of the treatment with therapy efficacy and safety control.

Aim. In patients after acute coronary syndrome (ACS) to study the effect of adherence to recommended therapy on the risk of cardiovascular events during a year after hospital admission, and to identify the main causes of low adherence to prescribed therapy. Material and methods. Patients with ACS (n=271), consistently admitting to the emergency cardiology department were included into the study. Complex therapy (acetylsalicylic acid (ASA), beta-blockers (BB), ACE inhibitors, statins) was prescribed to all patients. The drugs prescription rate was analyzed. The cardiovascular events (death, myocardial infarction, stroke, episodes of unstable angina, decompensated heart failure) were recorded for 12 months. The adherence of patients to recommended therapy was evaluated. Results. After hospital discharge ASA therapy was recommended to 98% of patients, BB — 95%, ACE inhibitors — 97%, statins — 63%. In 12 months only 73% of patients continued therapy with ASA, 66% — BB, 74% — ACE inhibitors, 44% — statins. The rate of hospital re-admission was significantly higher in patients with low adherence: 80% (n=32) vs 24% (n=55) among compliant patients. The main causes of hospital re-admission were decompensated heart failure (46%), recurrent episodes of angina (32%) or ACS (19%). Conclusion. A significant part of patients (about 1/3) terminates the recommended therapy within 12 months after ACS. Low adherence to therapy is often determined by subjective factors and associated with a 3-fold increased risk of cardiovascular events (RR 3.27; 95% CI 2.49-4.30; p=0.05).

Aim. To study the effect of amlodipine on the main indicators of systemic inflammation and its safety in patients with arterial hypertension (HT) in combination with ischemic heart disease (IHD) or diabetes mellitus (DM) type 2. Material and methods. Patients with HT (2-3 degree) associated with IHD or DM type 2 were included into the study. Patients were randomized into main group (n=30) receiving amlodipine 5-10 mg daily in addition to standard therapy (ACE inhibitors, beta-blockers, aspirin, statins, hypoglycemic agents), or into control group (n=30) receiving only standard therapy. Efficacy and safety of the therapy was evaluated by clinical, instrumental and laboratory parameters. Dynamics of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and C-reactive proteine (CRP) levels were determined to evaluate the activity of systemic inflammation. Treatment duration was 6-8 weeks. Results. Blood pressure reduction by 17.1±5.8/11.4±4.0 mmHg (p<0.05) was revealed in the main group and by 13.6±4.7/8.9±5.3 mm Hg - in the control one. A number of angina pectoris daily episodes decreased from 2.4±0.3 to 1.8±0.2 in the main group and from 2.2±0.2 to 2.0±0.4 in the control group. Angina attacks duration also decreased from 2.3 to 1.25 min in the main group. Significant reduction of IL-6 blood level from 16.6 (5.0; 22.5) to 6.5 (1.6; 12.7) pg/ml (p<0.05) and CRP blood level from 7.45 (2.56; 9.54) to 5.35(3.45; 6.23) mg/l (p<0.05) was observed in the main group (data is presented as median and interquartile range in the bracket). Blood levels of these inflammatory markers did not change significantly in the control group: IL-6 from 19.7 (7.3; 29.6) to 22.5 (13.6; 48.3) pg/ml, CRP from 6.85 (3.85; 8.23) to 7.05 (3.15; 9.12) mg/ l. Treatment tolerability was comparable in the groups.  Conclusion. Amlodipine is effective and safe antihypertensive agent. It reduces systemic pro-inflammation activity , which can promote atherosclerosis progression. Therefore, amlodipine can be recommended as first-line drug for the treatment of HT associated with DM and IHD.

Aim. To compare efficacy , safety and pharmacoeconomical characteristics of generic and original medicinal products of simvastatin in achievement of cholesterol and low density lipoprotein target levels. Material and methods. 38 patients with arterial hypertension accompanied by type 2 diabetes with dyslipidemia were included into the study. They had no clinically obvious ischemic heart disease and did not receive hypolipidemic pharmacotherapy for a month before the study start. The patients were randomized into group A or group B. Patients of group A (n=18) received original simvastatin, patients of group B (n=20) received generic simvastatin. Initial simvastatin dose was 20 mg daily. Lipid plasma profile, liver enzymes, creatine phosphokinase were evaluated every 4 weeks. Cost-effectiveness ratio was calculated. Results. 11 patients (61%) in group A and only 5 patients (25%) in group B (χ2=5.05; р<0.05) achieved cholesterol target level with simvastatin in dose of 20 mg daily in 3 months of the treatment. Creatine phosphokinase blood level did not increase significantly. Achievement of cholesterol target level cost 814 and 952 RUB per patient in groups A and B, respectively , in 1 month of simvastatin treatment. These costs were 643 and 417 RUB per patient in groups A and B, respectively , in 3 months of treatment. Conclusion. The original simvastatin in comparison with generic one has advantages in hypolipidemic effect. Safety profile is similar for both medications. Original simvastatin therapy has lower cost than this for generic simvastatin therapy in achievement of cholesterol target level in 1 month of treatment. In 3 months the cost of treatment per patient is 227 RUB higher for original medication in comparison with this for generic medication.

Aim. To study sulodexide clinical efficacy in patients with type 2 diabetes mellitus (DM) and ischemic heart disease (IHD) in prevention of contrast induced nephropathy (CIN). Material and мethods. Patients with type 2 DM and IHD who undergone X-Ray contrast intervention. The patients were randomized into 2 groups: 56 patients of the main group were i/v administered sulodexide (Vessel Due F , “Alfa Wassermann”, Italy) according to standard procedure; 56 patients of the control group were treated with unfractionated heparin. Results. The incidence of CIN in the main and control groups was, respectively , 16% and 42% (p<0.01). Reduction of microalbuminuria (MAU) was found in 89.3% of the sulodexide group patients. MAU dynamics in patients of control group was not observed. There were no deteriorations in echocardiography characteristics in patients of both groups. The reduction in  low density cholesterol and triglyceride plasma levels was observed in the main group. Sulodexide induced a lengthening of the activated partial thromboplastin time (from 30±0.6 to 34±0.5 s), without altering fibrinogen level. There were no thrombotic and hemorrhagic complications of endovascular intervention in sulodexide group. No one case of thrombocytopenia was observed. Higher risk of CIN in patients without sulodexide treatment compared with this in sulodexide treated patients was associated with multiple lesions of coronary arteries, diuretic intake in periprocedural period, contrast agent dose, duration of hospitalization, seriousness of intervention. Conclusion. Sulodexide therapy in patients with 2 type DM and IHD undergone X-Ray contrast intervention prevents renal dysfunction, providing antiproteinuric effect and correcting lipid metabolism and coagulation system disturbances.

Aim. To evaluate possibilities of psychometric visual analog scales (VAS) for assessment of the stable angina severity and efficacy of antianginal therapy. Material and Methods. Patients (n=259), receiving different pharmaceutical forms of organic nitrates as antianginal therapy were included into the study. Patients (n=130) treated with retarded form of isosorbide mononitrate were enrolled into the first group. Patients (n=129) treated with isosorbide mononitrate in conventional form or isosorbide dinitrate in moderately long-acting form were enrolled into the second group. Questioning with the "Scales of the patient condition" and Seattle Angina Questionnaire was performed in all patients. Spearman's rank correlation coefficient and Fisher test was used to estimate the relationship of parameters determined with standard questionnaire and the quality of life (QL) level, assessed with VAS. Results. After 3 months the integral QL index increased from 3.5±0.2 to 7.4±0.25 points in the 1st group and from 3.3±0.2 to 6.1±0.22 in the 2nd group. The functional dependence of the integral QL index, determined with VAS, and angina pectoris functional class (FC) was found in the linear regression model for the Fisher test. Integral QL index in the range of 10.0-7.6 corresponds to angina pectoris FC I, 7.5-5.3 to FC II, and 5.2-3.9 to FC III. Integral QL index lower than 3.8 only hypothetically could correspond to angina pectoris FC IV. Conclusion. The VAS clinical  implementation is a simple and demonstrative method that adequately reflects the angina severity and the efficacy of antianginal treatment.

Aim. To study changes in acute coronary syndrome (ACS) patient hospital management in nonivasive primary vascular center in 2007-2009. Material and methods. 188 (RECORD register data) and 180 (RECORD-2 register data) patients with ACS were admitted to the emergency cardiology department in November 2007 and November 2009, respectively. Results. Thrombolytic therapy was performed in 62 patients in 2009 whereas in 2007 no one patient received this therapy because of thrombolytic drugs absence. Only 39.4% of patients were treated with unfractionated heparin in 2007. In 2009 50% of patients received unfractionated heparin, 12.5% of patients – enoxaparin and 7.4% - fondaparinux. 2.7% of ACS patients were transferred to the regional vascular center in 2007 and 3.9% -  in 2009. Conclusion. Creation of the primary vascular center led to improvement of ACS patient hospital management, and move it closer to modern guidelines. However hospital lethality did not changed (3.3% and 3.7% in 2009 and 2007, respectively).

Pedigree of the family from Krasnoyarsk city with hereditary disorders of intracardiac conduction was studied. The diagnosis of each family member was verified by electrocardiography (ECG), echocardiography , bicycle ergometry , ECG Holter monitoring. The family 10-year follow-up showed familial aggregation of intracardiac conduction disorders in grandson, niece, son of the proband niece, ie, in the III-degree relatives. Family history of III-degree relatives with intracardiac conduction disorders and discordant pathology is identified.

Aim. To study the clinical efficacy of corrective therapy of anemia in patients with chronic heart failure (CHF) and ischemic heart disease (IHD). Material and methods. Patients (n=58; 32 female, 26 male; aged 47-85 years) with IHD and CHF with left ventricular ejection fraction (LVEF) <45% were included into the study. They received basic CHF therapy. Patients (n=12) with iron deficiency anemia also received erythropoietin and iron containing drugs during 12 weeks. Clinic and instrumental examination was performed before and after the treatment. Exercise tolerance was evaluated by 6-minute walk test. Results. The anemia was revealed in 14 (24.8%) patients, including 12 patients with iron deficiency anemia. By the end of 12 week therapy with erythropoietin and iron containing drugs significant increase (+36%) in 6-minute walk distance and LVEF (+32.5%), improvement of CHF NYHA functional class were observed. Besides increase in hemoglobin (+12.5%; p<0.001) and hematocrit (+5.8%; p<0.001) levels, as well as increase in red blood cells number (+8%; p<0.001) were found. Conclusion. In patients with CHF and IHD correction of anemia with erythropoietin and iron containing drugs additionally to the basic CHF/IHD therapy leads to a significant clinical and functional improvement.

Aim. To compare the safety and efficacy of pre-hospital thrombolysis with tenecteplase and hospital thrombolysis with alteplase. Material and Methods. Pre-hospital thrombolytic therapy with tenecteplase (n=15) and hospital thrombolysis with alteplaza (n=60) in patients with acute coronary syndrome and acute ST-segment elevation myocardial infarction were analyzed in retrospective comparative study. Time characteristics of thrombolysis and its efficacy and safety were assessed. Results. The mean time from patients emergency medical service call to pre-hospital thrombolysis was 51.8±1.23 min, whereas to hospital thrombolysis 106.5±2.15 min (p<0.05). The effective hospital thrombolysis was observed in 68.3 and 83.3% of patients according to ECG (>50% resolution of ST-segment elevation) and coronary angiography criteria, respectively. The effective pre-hospital thrombolysis was registered in 93.3% of patients as demonstrated with ECG and coronary angiography. Conclusion. Pre-hospital thrombolysis in patients with acute coronary syndrome was performed by 54.7 min earlier than hospital thrombolysis was. This can improve the patient prognosis.

Problems of antihypertensive therapy are discussed in the light of the present epidemiological situation with arterial hypertension. ACE inhibitors have a special place among the antihypertensive drugs. Advantages and evidence base of ACE inhibitors representative — zofеnopril highlighted. Special attention is given to combined antihypertensive therapy , particularly combination of zofenopril and hydrochlorothiazide.

The world publications data about the impact of consumption and the fatty acids ratio in consumed fats on the development of cardiovascular diseases and acute complications due to atherothrombosis is presented. The role of some fat characteristics is discussed: hydrogenous saturation with different number of double bonds, various lengths of hydrocarbonic chains and molecule geometry , etc. Fat structure is more crucial for cardiovascular risk than total amount of consumed saturated fat. Favorable fat structure should include physiologic amounts of saturated fatty acids (8-10%), polyunsaturated fatty acids, especially n-3 long-chain, a significant amount (up to 20% of calories) of monounsaturated fatty acids, a very small amount of trans fatty acid form. Such a fatty product is useful in antiatherogenic diets.

Recent data and perspectives of antithrombotic therapy in patients with atrial fibrillation (AF) are highlighted. The main statements of current Russian and international guidelines about thromboembolic events prevention in AF patients are presented. Special attention paid to new agents for oral anticoagulation therapy , last information about their efficacy , safety and potential of application.

Antiplatelet agents are a necessary component of modern therapy of atherosclerosis. The difficulties of the antiplatelet treatment lie in balance between the necessary therapeutic effect and the risk of excessive action, leads to the bleeding. The ability to monitor antiplatelet pharmacodynamics is still very limited. Pharmacology of antiplatelet drug has been developing rapidly. New antiplatelet drugs are on their way to clinical application — prasugrel, ticagrelor , elinogrel, thromboxane receptor inhibitors, thrombin receptors inhibitors. Clinical pharmacology of these drugs is different. Practitioner should know their specifics to avoid the development of iatrogenic complications.

The main events of the Congress of the European Society of Cardiology (ESC) held in Paris, (August 27-31, 2011) are highlighted. The results of recently completed randomized controlled studies, pharmacoepidemiological studies, additional analysis of a number of previously completed studies, new clinical ESC guidelines, as well as results of debates on controversial issues in cardiology , assessment of clinical trials data and therapy compliance are presented.