The problem of vascular comorbidity in patients with cardiovascular diseases, its effect on the cardiovascular risk, general causes and approaches to the prevention and treatment of vascular comorbidity are considered.
ORIGINAL STUDIES 
Arterial hypertension is a disease which leads to severe negative social and economic consequences. Pharmacoepidemiologic studies allow assessment of present situation on high blood pressure (BP) treatment and search of ways of its efficacy improvement.
Aim. To study treatment of hypertensive patients who had visited the cardiology referral clinic for the first time and to assess treatment dynamics over the following 6 months with the estimation of its efficacy.
Material and methods. The study included two steps. At the first step a primary sample of the study participants was formed out of hypertensive patients who had visited for the first time a cardiologist in one of the Moscow district cardiologic dispensary in 2010 with the further completion of expert cards in accordance with the primary medical documentation (n=1766). At the second step the phone survey was conducted 6 months after the first visit with the completion of special questionnaires (n=1419).
Results. Recommendations for antihypertensive treatment given to the cardiologic dispensary patients are in line with the current guidelines, and 6 months after the first visit 91% of the patients had continued antihypertensive treatment. However, the efficacy of BP control turned out to be low: target BP level was only detected in 28.8% of the patients, and 36.7% of the respondents developed hypertensive crises during the 6 months.
Conclusion. Despite the follow-up in the referral clinic and the intake of the prescribed drugs the patients revealed low efficacy of BP control. The reasons for this fact require further investigation. Probably, the improvement of BP control requires implementation of special education and motivational techniques as short-term contact with specialists does not lead to high efficacy of antihypertensive treatment.
Aim. To provide final data on the three-year period of the inclusion of patients; to give most accurate "portrait" of patients hospitalized with a brain stroke within the framework of the LIS-2 register (Lyubertsy study of mortality in patients after stroke).
Material and methods. All patients (n=960) admitted to the Lyubertsy district hospital №2 with stroke for the period from 01.2009 to 12.2011 were included into the study.
Results. Men accounted for 37.5%, women - 62.5%, mean age was 71.1±9.8 years. The history of hypertension was present in 833 patients (86.8%), atrial fibrillation in 252 (26.8%) patients, 199 (20.7%) patients had previously undergone stroke. In-hospital mortality was 21.6% (207 patients had died; mean age 72.9±9.8 years). Low frequency of the antihypertensive therapy (34.5%), lipid-lowering therapy (0.7%), antiplatelet agents (5.7%), anticoagulation therapy prescription in patients with atrial fibrillation was detected.
Conclusion. Insufficient assignment of drugs with a proven effect on the prognosis in patients with risk factors prior to the development of the reference stroke draws attention. High incidence of recurrent strokes indicates an underactive secondary prevention.
Aim. To analyze the impact of the SLCO1B1*5 (c.521T> C) and LIPC (C514T) genes polymorphisms on the efficacy of atorvastatin therapy and the incidence of the combined endpoint in patients after myocardial infarction (MI).
Material and methods. 121 patients with MI aged 45-75 years were included into the study. All patients were prescribed atorvastatin. A group of 65 people in whom lipid levels were studied at baseline and after 3 months of atorvastatin treatment was formed to evaluate the efficacy of statin therapy. Genetic polimorphism of SLCO1B1*5 (c.521T> C) and LIPC (C514T) was determined using polimerase chain reaction. The prognosis was assessed by clinical outcomes after 3 months of follow-up, based on the achievement of the combined endpoint MACE (Major Adverse Cardiac Events), which included cardiovascular deaths, recurrent MI, hospitalization for progressive angina, unplanned coronary revascularization.
Results. Patients with SLCO1B1 c.521СC genotype had no significant reduction in the levels of atherogenic lipids (p>0.05), while patients with TT and TC genotypes demonstrated significant reduction in atherogenic cholesterol fractions (p<0.05). Allelic polymorphism of LIPC (C514T) gene has no influence on the atorvastatin treatment efficacy. The SLCO1B1 and LIPC (C514T) genes polymorphism has no impact on the three-month prognosis after MI.
Conclusion. The SLCO1B1 polymorphism should be taken into consideration while personalised prescribing of atorvastatin to patients with MI.
Aim. To evaluate antihypertensive effect of a 12-week therapy with fixed combination of enalapril and indapamide on insulin resistance (IR), glucose, lipid and purine metabolism in patients with arterial hypertension (HT) and diabetes mellitus (DM) type 2.
Material and methods. 30 patients with HT stage II-III and DM type 2 aged 40-65 years were included into the study. Antihypertensive therapy with fixed-dose combination of enalapril (10 mg) and indapamide(2.5 mg) was initiated for 12 weeks. The level of office systolic blood pressure (SBP) and diastolic blood pressure (DBP), the concentration of glucose, glycosylated hemoglobin, basal insulin, uric acid, fasting lipid profile in the venous blood and IR were assessed.
Results. Target blood pressure values were achieved in all patients. After 12 weeks of treatment, there were significant changes in office SBP (Δ%=-23.6) and DBP (Δ%=-12.9) as compared with the baseline values. Metabolic index, characterizing the degree of insulin resistance, decreased significantly by 22.5% (17.8±1.4 baseline vs 13.8±1.4 after 12 weeks of treatment) and atherogenic index decreased by 18.4% (3.16±0.2 baseline vs 2.58±0.17 after 12 weeks of treatment, p<0.05). There was no deterioration of glucose and purine metabolism during the follow-up.
Conclusion. Combined antihypertensive therapy with enalapril and indapamide for 12 weeks significantly lowers SBP and DBP, the degree of IR, does not affect carbohydrate, lipid and purine metabolism in patients with HT and DM type 2, i.e. it’s metabolically neutral.
NOTES FROM PRACTICE 
One of the three clinical examples of hospital thrombolysis using Russian thrombolytic agent recombinant protein comprising an amino acid sequence of staphylokinase is described. The trial was held in Chelyabinsk Regional Vascular Centre of specialized medical care for patients with acute coronary syndromes. Each of the three patients had similar reasons for systemic intravenous thrombolysis: hospitalization with ST-segment elevation myocardial infarction, unavailability of coronary interventions due to the X-ray operating room occupancy, high need for the reperfusion therapy in the setting of significant acute myocardial ischemia. In all the cases the pharmacologic reperfusion with recombinant protein comprising an amino acid sequence of staphylokinase was successful, hereafter percutaneous coronary interventions were performed. There were no complications registered.
PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY 
Aim. To develop a method for the assessment of quality of medical prevention of recurrent stroke and its’ testing using the results of the LIS-2 register (Lyubertsy study of mortality in patients after stroke).
Material and methods. The scale evaluation of the quality of therapy for the prevention of recurrent stroke developed in accordance with the modern clinical practice guidelines, as well as the recurrent stroke prevention index (RSPI) for this assessment were elaborated. The analysis of the therapy was performed in patients after stroke in LIS-2 registers (n=219). The assessment of the quality of treatment was performed using RSPI, the influence of the index results on the in-hospital mortality was studied.
Results. Two groups of patients [with RSPI=0 (n=137) and RSPI>0 (n=82)] were formed on the basis of the results evaluation via RSPI. Significant differences between groups were not found. At the same time higher in-hospital mortality (p=0.014; χ2 Pearson) was detected in patients with RSPI=0; relative risk of in-hospital death (after adjustment for sex and age) was 2.04 [1.07-3.91] (p=0.031). Analysis of the length of survival and duration of hospital stay was performed in both groups using the Kaplan-Meier method. In-hospital mortality was significantly higher in patients with RSPI=0, which was confirmed by the log-rank test (p=0.032).
Conclusion. The results of the quality of medical care assessment in accordance with the developed method are significantly related to the outcomes during the stay in a hospital. The developed method, based on current clinical recommendations, can serve as an example of the implementation of evidence-based medicine in actual practice.
INNOVATIVE CARDIOLOGY 
Nowadays aortic stenosis is the most common valvular pathology in Europe and North America and its incidence increases with age. Long asymptomatic period, the duration of which varies in different patients, is the main clinical feature of this disease. In 80% of asymptomatic patients with the severe aortic stenosis the onset of clinical signs that significantly worsen the prognosis, occurs within the next 4 years. So, if two-year survival rate in asymptomatic period is at least 50%, a 5-year survival rate in patients with symptomatic aortic stenosis without surgery, according to some estimates, is reduced to 15%. Therefore, these patients do not have any alternative to surgery. At that, high risk of complications after surgery and perioperative mortality related to them are the most essential problems of surgical treatment of the aortic valve diseases in the setting of cardiopulmonary bypass. This was the decisive factor for the development of alternative methods of surgical correction of the aortic valve diseases. Indications and contraindications for transcatheter aortic valve implantation (TAVI), which is currently a "disruptive technology", are discussed. Different models of aortic valve prostheses, the use of which is confirmed by the available evidence, are considered. The most important unsolved problems of TAVI use in recent times are mentioned in brief. More than 300 TAVI procedures have been performed in Russia recently which definitely does not cover the actual needs.
POINT OF VIEW 
For prevention of thromboembolic events in patients with non-valvular atrial fibrillation (NVAF) the following types of antithrombotic therapy are used: anticoagulant therapy with vitamin K antagonists (warfarin), antiplatelet therapy (acetylsalicylic acid) and novel oral anticoagulants such as apixaban, rivaroxaban and dabigatran. Along with clinical efficacy and safety profile one of the main characteristics of any medical technology is economic value and cost-effectiveness. The objective of this review was to describe pharmacoeconomic aspects of using apixaban for stroke and other cardiovascular events prevention in patients with NVAF. Results of the previously published cost-effectiveness studies demonstrated that apixaban was projected to increase life expectancy of the patients with NVAF compared with standards of care warfarin and aspirin, novel oral anticoagulants rivaroxaban and dabigatran. At the same time apixaban is expected to be cost-effective alternative from the Russian Federation national healthcare budget perspective.
The conclusion of the Expert Council "Challenging problems of hypertension management: the effect of increased heart rate and comorbidities on the choice of antihypertensive therapy in practice of cardiologist and therapist" is presented. Topical issues of hypertensive patient’s treatment, the role of heart rate in hypertension and ways to influence it are considered. The possibility of treatment of hypertensive patients with trandolapril/verapamil SR fixed combination is analyzed separately. The data on the clinical efficacy and protective effects of trandolapril/verapamil SR fixed combination are presented.
The helical ventricular myocardial band of Torrent-Guasp is a new concept, which provides strong grounds for reconciliation of some important aspects in cardiovascular medicine. Oblique fiber orientation provides left ventricular rotation, which in addition to radial thickening and longitudinal shortening, is predicted as an essential component of the effective left ventricular pumping. Left ventricular rotation can be measured in clinical practice noninvasively using echocardiography and this provides new opportunities for the assessment of different aspects of left ventricular mechanical function.
Aspects of heart rate-lowering therapy in patients with chronic heart failure using If-channel blocker ivabradine are discussed. The evidence-based data on ivabradine use reveal its advantages, disadvantages and place in the treatment of cardiac patients.
Evaluation of platelet function with subsequent modification of antiplatelet therapy regimen is one of the areas of personalized medicine. Analysis of the causes of inadequate antiplatelet action of clopidogrel, the association of residual platelet reactivity with clinical outcomes and a review of the research on the change of antiplatelet therapy in patients with ischemic heart disease after percutaneous interventions based on the results of platelet function testing, were the aim of this review.
CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY 
A complex system of hemostasis regulation, insufficient data on drugs pharmacokinetics, multiple factors effecting treatment, including patient’s adherence to therapy, that can lead to the need for the dosage regimen specification are presented.
Statins are lipid-lowering drugs with proven efficacy that reduce cardiovascular risk and are well tolerated by most patients. Myopathy as a side effect of statin therapy is one of the most common reasons for their withdrawal. Its severity can range from asymptomatic increase of serum CPK to life-threatening rhabdomyolysis. Therefore it is necessary to remember about the possibility of its occurrence.
The exact molecular mechanisms of muscle damage by statins are still unknown. Various hypotheses are suggested in this respect: fatty acid oxidation disorders, mitochondrial dysfunction, increased protein degradation in myocytes due to changes in atrogin-1 and ubiquitin activity, activation of autoimmune processes, intracellular depletion of essential metabolites, destabilization of cell membranes, impaired expression of genes involved in apoptosis and protein degradation. The theory that the reduction of intramuscular CoQ10 level is the cause of myopathy prevails. Additional intake of CoQ10 seems promising, but is not evidence-based.
OUR MENTORS 
Pomerantsev Vladimir Petrovich (1925-2000).
Report on activity of editorial board of “Rational Pharmacot herapy in Cardiology” in 2014.
Information letter.
Information letter.
ISSN 2225-3653 (Online)