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Introduction. The results from foreign and local studies demonstrate that more than a half of patients with cardiovascular diseases do not take medication in compliance with doctors’ recommendations. The search for significant barriers to optimal medication adherence might improve the development of adherence control measures in patients with stable coronary artery disease (SCAD) in routine clinical practice of primary care.Aim. To study the nature and incidence of potential barriers to optimal medication adherence and their association with social and demographic parameters in patients with SCAD.Methods. This publication describes the fragment of the study “PHARMCARE” in which 123 coronary patients were included. Data on demography, social status, medical history and pharmacotherapy were registered. The barriers to medication adherence were identified by means of validated scale (questionnaire) SEAMS (Self-Efficacy for Appropriate Medication Use Scale). Data analysis was conducted by descriptive statistics and regression modeling.Results. The analysis of incidence of barriers to medication adherence allowed to identify the list of most significant ones: “fear of side effects”, “intake of several different medicines each day”, “intake of medicines more than once a day”, “medicines look different than usual”, “normal routine gets messed up”, “busy day planned”, “no one reminds to take medicines” and “staying away from home”. More than a third of all the respondents reported at least one of barriers (37%), that was in major cases “fear of side effects” (22%). Linear one-factor modeling revealed association of number of significant barriers in patients with level of their education (р=0,009) and presence of partner or caregiver (р=0,001), that was also confirmed by the multivariate model. Less barriers were identified in coronary patients that had partner or caregiver (р=0,009) and higher education (р=0,045).Conclusion. The study results revealed that the significant barriers to optimal medication adherence in out-patients with SCAD were related either to patients’ behavior or to pharmacotherapy profile. Uncertainty in overcoming barriers was most typical for single patients without higher education. The obtained results should be taken into consideration when develop strategies for improvement of medication adherence in patients with SCAD in primary care practice.

Introduction. Incidence of inadequate medication adherence to secondary prevention medications among Russian coronary patients is around 50 %, but the question, how this might influence on the risk of unfavorable outcomes, still has no answer.Aim. To determine the effect of medication adherence on the risk of unfavorable clinical outcomes in outpatients with stable coronary artery disease (CAD). Methods. Prospective observational cohort study was conducted. 281 subjects with verified stable CAD were included in line with the pre-specified criteria. Medication adherence was measured by validated 8-item Morisky scale. Data on cardiovascular events were obtained over the 24-month monitoring period. Study endpoint was a composite cardiovascular event (all-cause mortality, acute myocardial infarction, unstable angina, revascularization surgery, acute heart failure, decompensation of chronic heart failure). Survival analysis by Kaplan — Meier method was performed.Results. 26.0 % of coronary outpatients had low medication adherence (below 6 points by Morisky scale). Groups of patients with satisfactory and low medication adherence were comparable by demography, medical history, and pharmacotherapy. Over the monitoring period composite cardiovascular event was registered in 115 patients (40.9 %). 46.6 % of patients from the low adherence group suffered from the composite event, 38.9 % — from the satisfactory adherence group. Time to the event was lower in the low adherence group — median 24.2 (IQR 7.5-29.2) vs. median 27.9 (IQR 17.4-34.5) months. Cumulative incidence of the composite cardiovascular event over the monitoring period was higher in the low adherence group compared to satisfactory adherence group (p=0.032; log-rank test), also when adjusted for history of cardiovascular events (p=0.033; log-rank test). Satisfactory medication adherence reduced risk of composite cardiovascular event by 37 % (HR 0.63; 95 % CI 0.42-0.94; р=0.025; Cox-regression adjusted for history of cardiovascular events).Conclusion. Coronary outpatients with satisfactory medication adherence had lower risk of cardiovascular events over the 24-month monitoring period.

Relevance. As part of the conducted open non-randomized phase I clinical trial the pharmacokinetics (PK) of the first Russian novel antiplatelet agent Angipur (nonpeptide glycoprotein IIb/IIIa receptor inhibitor) was studied.Aim of the research was to evaluate PK parameters of Angipur in healthy volunteers after single dose ascending infusions.Methods. 20 male healthy volunteers were enrolled in this phase I trial. Angipur (0.02% concentrate solution for infusion) was administered to every subject in single doses 0.015, 0.05, 0.09 mg/kg for 3 consecutive days. PK parameters were evaluated.Results. After single intravenous administration of doses 0.015, 0.05, 0.09 mg/kg to healthy volunteers the peak plasma concentration of Angipur was reached at the end of the infusion, and then the plasma concentration rapidly decreased 15 minutes after the end of the infusion followed by slow decrease for 12 hours. Dose proportionality for key PK parameters was established. After single infusions of doses 0.015, 0.05, 0.09 mg/kg mean AUC0-t was 27.11, 92.04 and 180.39 ng× h/ml; mean AUC0-¥ – 37.03, 125.76 and 239.61 ng×h/ml; mean Сmax – 12.44, 46.1 and 92.48 ng/ml; mean Vd – 304.01, 299.67 and 252.96 l; mean Т1/2 – 6.72, 6.84 and 6.06 h; Сl – 32.19, 32.29 and 31.55 l/h; kel – 0.1073, 0.1109 and 0.1257 l/h; MRT – 8.94, 8.93 and 8.18 h.Conclusion. Pharmacokinetics of Angipur in studied doses demonstrated linearity, rapid reaching of Сmax immediately after the infusion and the high distribution of the drug in tissues and biological fluids of the human organism..

Introduction. The results of local studies indicated that medication adherence of coronary outpatients is low (not more than 60 %). The search for significant predictors of adherence to recommended treatment might allow tailoring specific strategies to control adherence for further optimization of the pharmacotherapy of coronary artery disease (CAD) in routine primary care practice. Aim. To determine the factors associated with medication adherence in outpatients with stable CAD. Methods. This paper describes the results of the fragment of randomized controlled study of the effects of Pharmacy Care Program on medication adherence of coronary outpatients, that was conducted in 2019-2020 in one of the primary care clinics of Moscow. 123 subjects with stable CAD were included in line with the pre-specified criteria. Demography, social status, medical history, pharmacotherapy, healthcare burden data were registered. Medication adherence was measured by validated questionnaire MMAS-8 (8-item Morisky Medication Adherence Scale). The analysis of predictors of adherence was performed by linear regression. Results. Simple regression analysis revealed the list of parameters, that showed statistically significant (or as statistical trend) association with medication adherence of coronary patients in univariate models. The level of medication adherence was associated with patient’s having a partner or caregiver (p=0,002), higher education (p=0,009), additional medicinal maintenance (p=0,006). Medication adherence did not depend on medical history and pharmacotherapy characteristics, but the association of high values of low-density lipoproteins cholesterol (LDL-C) (p=0,001) with suboptimal adherence was demonstrated. Good medication adherence was associated with more frequent visits to general practitioner (p=0,036) and (as statistical trend) to cardiologist (p=0,093). The multivariate regression analysis revealed two positive independent predictors of medication adherence - patient’s having a partner or caregiver (р=0,015) and regular visits to cardiologist (р=0,025). Also, the negative association was confirmed for high LDL-C (р=0,002). Conclusion. Patient’s having a partner or caregiver and regular visits to cardiologist were revealed as independent predictors of good medication adherence of coronary outpatients. Subjects with suboptimal adherence had higher LDL-C.

Aim. To study medication adherence in elderly patients with coronary artery disease (CAD) in primary care practice.Material and methods. The study conducted in out-patient clinic of Moscow city. 293 elderly (≥65 years) patients with established CAD included. The following patient data obtained via electronic medical record system: demography, medical history, modifiable risk factors and prescribed pharmacotherapy. Level of medication adherence measured by Morisky scale (MMAS-8) via telephone survey.Results. According to Morisky scale high adherence was identified in 146 (49.8%) elderly patients, moderate adherence – in 99 (33.8%) patients, low adherence – in 48 (16.4%) patients. Analysis of specific questions of the scale done in non-adherent patients revealed signs of unintentional non-adherence due to forgetfulness (45.9%) and signs of intentional non-adherence due to patients feeling worse (35.8%) or better (28.4%). By means of dichotomic interpretation of Morisky scale results the population under research was divided into two groups: 147 (50.2%) non-adherent patients and 146 (49.8%) – totally adherent patients. These groups were comparable in terms of sex (female 71.2 vs 68.0%; p>0.05) and age (median 73.5 vs 73.0 years; p>0.05) distribution, and medical history: myocardial infarction (39.0% vs 38.8%), atrial fibrillation (37.0 and 41.5%), chronic heart failure (90.4% vs 91.2%), diabetes (26.7% vs 24.5%). There were fewer smokers in adherent group (0.7% vs 6.5%; p0.05). Drugs that improve prognosis were also prescribed comparably: antiplatelets (66.4% vs 61.9%; p>0.05), anticoagulants (36.3% vs 44.9%; p>0.05), statins (82.2% vs 79.6%; p>0.05), renin-angiotensin system inhibitors (89.0 and 87.8%; p>0.05). Adherent patients had lower mean values of lipids: total cholesterol (4.7±1.2 vs 5.2±1.4 mmol/l; p0.05).Conclusion. Half of elderly patients with CAD are non-adherent to treatment in primary care setting. Medical history and structure of pharmacotherapy do not influence level of adherence in this population. Among adherent patients fewer individuals smoke and mean values of lipids are lower. Non-adherent elderly patients cause higher load on general practitioner, supplementary pharmaceutical provision program provided no better adherence in the population under research.

Aim. To study predictors of primary care physician adherence to guideline-recommended pharmacotherapy of stable coronary artery disease.Material and methods. This pharmacoepidemiologic cross-sectional study was conducted in primary care setting of Moscow. 805 patients (mean age 68.9±9.9 years, males 51.4%) with established stable coronary artery disease (SCAD) were included. Demography, medical history, prescribed pharmacological treatment data were obtained. Physician adherence to guideline-recommended pharmacotherapy (GRP) of SCAD was evaluated based on the Class I guideline recommendations. Pharmacotherapeutic guideline adherence index (PGAI) was introduced as composite quality indicator, calculated in line with “all-or-none” rule and in regard with documented contraindications. To search for predictors of adherence the patient population was divided in two groups by level of physician adherence measured by PGAI. Statistical analysis was performed by IBM SPSS Statistics 16.0, the level of statistical significance was set at p

The article emphasizes the need to develop and apply standard operating procedures (SOP) as an instrument of quality management system of rational pharmacotherapy in primary care practice. To justify the reasonability of SOP implementation into outpatient clinical practice pharmacoepidemiologic analysis of the quality of care provided to patients with stable coronary artery disease in the primary care setting of Moscow over two consecutive periods was used. tte key variables of interest were characteristics that reflected physician adherence to clinical practice guidelines.

In this article the authors address the problem of poor medication adherence in patients with cardiovascular disease. Poor medication adherence significantly reduces efficacy of pharmacotherapy thus increasing risk of cardiovascular complications and higher treatment costs in routine clinical practice. This problem was first raised by a few foreign scientists in the 90s and then officially recognized by the World Health Organization in 2003. The article presents review on the prevalence of low medication adherence in patients with cardiovascular disease and describes key factors associated with decreased adherence. An overview of widely used indirect methods to measure medication adherence is presented as well. On the way to solve this problem, the development and implementation of various measures and interventions to improve medication adherence is actively carried out in recent years. The results of the most significant studies on the effectiveness of such interventions are also presented in the article. Positive influence on patient adherence was demonstrated, however, only a number of studies reported reduction of the risk of unfavorable clinical outcomes of cardiovascular diseases. This confirms the need to further study the problem of medication adherence focusing on routine clinical practice in Russia.

Aim. To study the tolerability, safety, pharmacokinetics (PK) and pharmacodynamics of single intravenous infusions of Angipur in healthy male volunteers.Material and methods. The Phase I trial included 20 healthy male volunteers (mean age, 30,8±7,7 years; mean body weight, 77,4±12,1 kg). Angipur (0,02% concentrate for solution for infusion) was administered to every subject in single doses 0,015, 0,05, 0,09 mg/kg for 3 consecutive days. Volunteers were divided in 6 groups (1, 1, 3, 5, 5, 5); every following group was recruited only after the previous one finished the study. The following were assessed: rate and severity of adverse events (AEs), key PK parameters of Angipur and its antiplatelet activity by impedance aggregometry.Results. No moderate or severe AEs, as well as no serious AEs were reported according to obtained data of clinical and laboratory monitoring of healthy subjects. Totally 6 mild AEs were registered in 4 subjects. Four AEs (mild hematological deviations and episode of nose bleed) were classified as possibly related to study drug and 1 AE (positive fecal occult blood test) — probably related. Key PK parameters of Angipur in single intravenous doses 0,015, 0,05 и 0,09 mg/kg were determined as follows: Cmax — 12,44±4,689, 46,10±14,295, 92,48±33,896 ng/ml; Vd — 304,01±55,300, 299,67±64,244, 252,96±47,790 l; T1/2 — 6,72±1,290, 6,84±2,341, 6,06±2,287 h; Cl — 32,19±6,919, 32,29±8,357, 31,55±10,113 l/h, respectively. Dose proportionality (linear PK) for parameters Cmax, AUC0-t and AUC0-∞ was established. Dose-dependent reduction of ADP-induced platelet aggregation degree and area under curve was revealed at period of 15 min to 2-4 h after Angipur infusion in doses 0,05 and 0,09 mg/kg.Conclusion. Results of phase I clinical trial demonstrated good tolerability of single intravenous infusions of Angipur (0,015, 0,05 и 0,09 mg/kg) in healthy subjects. We determined key PK parameters and indicated dose-dependent antiplatelet activity of Angipur.

Aim. To assess the effects of the Pharmacy Care Program on medication adherence in outpatients with stable coronary artery disease (SCAD).Material and methods. An open randomized controlled study was conducted in primary care clinic over the period of 2019-2020. All subjects (n=126) were randomized at visit 1 into the multifaceted intervention group (n=63) or control group (n=63) and invited 12 months after to visit 2. Patients of intervention group were included into the Pharmacy Care Program, which consisted of the following components: pharmacist-led counseling, provision of education materials and 7-day pillbox, weekly SMS-reminders. Medication adherence was measured initially and at the end of the study period by means of eight-item Morisky Medication Adherence Scale (MMAS-8) and Self-Efficacy for Appropriate Medication Use Scale (SEAMS).Results. The implementation of the Pharmacy Care Program improved medication adherence in SCAD outpatients with MMAS-8 median score of 7,0-8,0 (p

Background. Currently, the main treatment for Gaucher disease is enzyme replacement therapy. Recombinant glucocerebrosidase (imiglu-cerase) is the first biotechnological drug for enzyme replacement therapy with proven clinical efficacy and safety for the treatment of patients of different ages with Gaucher disease type 1 and type 3, used in clinical practice since 1994. In Russia, within the framework of the “Pharma 2020” pharmaceutical industry development strategy, the first biosimilar of imiglucerase, the drug Glurazyme®, was developed. The obtained results of preclinical studies became the basis for a phase I randomized comparative crossover clinical trial.The objective of the study was to assess the short-term safety and pharmacokinetic parameters of Glurazyme® in comparison with the Cerezyme® after a single intravenous administration to healthy volunteers.Materials and methods. 23 healthy volunteers aged 18—45 years were included in a 3-stage clinical trial. The study during the 1st and 2nd stages was open, randomized, comparative, crossover. At the 1st stage, volunteers from the 1st group received the Glurazyme®, from the 2nd group — the Cerezyme® once in doses of 30 U/kg. At the 2nd stage, Cerezyme® was administered to the 1st group, Glurazyme® - to the 2nd group once at doses of 30 U/kg. After the end of the 1st and 2nd stages, the 3rd stage was carried out for the 3rd group (n = 5) with the administration of the test drug once at a dose of 60 U/kg.Results. For all studied pharmacokinetic parameters, after administration of the test and reference drugs in doses of 30 U/kg, 90 % confidence interval was in the range from 80 to 125 %, which indicates the pharmacokinetic compared drugs equivalence. A total of 6 adverse events of mild and moderate severity were recorded. Of these, 4 adverse events were noted after administration of the study drug and were not associated with its administration. A comparative analysis of safety assessment parameters in this study (frequency and severity of adverse events, physical examination of healthy volunteers with an assessment of vital signs, laboratory tests, electrocardiography) did not reveal intergroup differences.Conclusion. The pharmacokinetic equivalence of the Glurazyme® and the reference drug in a dose of 30 U/kg has been established. A nonlinear dependence of the main pharmacokinetic parameters on studied drug administered dose was revealed. Safety and the absence of adverse reactions after a single injection of the study drug are shown.

Aim. To conduct a pharmacoepidemiologic analysis of lipid-lowering therapy (LLT) in outpatients of different ages with coronary artery disease (CAD).Material and methods. A total of 805 medical records of outpatients with CAD were analyzed in this pharmacoepidemiologic, cross-sectional study conducted at primary care facility of Moscow. The total sample of patients was divided into 3 age groups: group 1 — 0,05). Dual LLT was prescribed rarely (4,9%, 3,9%, 0,9%, respectively), especially in patients ≥75 years (p0,05); patients ≥75 received rosuvastatin less often (p0,05), as well as the proportion of patients not achieved target LDL-C 0,05).Conclusion. The study demonstrated no significant influence of patient age on LLT prescription rates, LDL-C control, and prevalence of irrational drug combinations in outpatients with CAD. Rates of dual LLT, structure and intensity of statin therapies differed depending on age groups.

Aim. To analyze changes in the pattern of lipid-lowering therapy (LLT) in outpatients with stable coronary artery disease (SCAD) over the 7-year period.Material and methods. This pharmacoepidemiological, retrospective, cross-sectional, two-stage study was conducted on the basis of primary care facility of Moscow. We analyzed 1,834 and 805 medical records of patients with SCAD at the first (2011) and second (2018) stages, respectively. Data on demography, medical history, lipid profile, and administrated LLT were collected. Statistical analysis was performed using SPSS Statistics V16.0 and MS Excel. Differences were considered significant at p

This article discusses one of the most disputable issues in national clinical research practice in healthy volunteers. Regulatory requirements forbid to assess even minor deviations of laboratory parameters from reference intervals as not clinically significant. Authors made analysis of such requirements from positions of foreign and national guidelines of early phase clinical research and with regard to their own experience in the field. As an important part of this work, retrospective analysis of the laboratory test results data of healthy volunteers taken from several clinical trials was conducted. The aim of this analysis was to establish the rate of not clinically significant deviations from reference intervals. The results of the analysis revealed rather high rate of not clinically significant deviations of some laboratory parameters from reference intervals in volunteers with confirmed status “healthy”. Authors noted that developers of clinical trial protocols have no unified approach to generate list of necessary laboratory tests and methods of assessment of the results. Ethical and financial aspects of the problem under discussion are also touched in this article. In conclusion, authors suggest the scale of clinical significance assessment of deviations of basic laboratory parameters from reference intervals as one of the possible options of optimizing current regulatory requirements.

This article discusses important problem of early phase clinical trials – over-volunteering. The overlapping or dual enrollment of healthy volunteers is a potential high risk not only to study subjects, but also to commercial sponsors because it could cause the delay in advancement of promising drug candidates. The problem of over-volunteering is payed special attention by clinical research professionals in foreign countries. Guidelines for early phase clinical trials recommend implementation of different control and prevention measures of multiple enrollment. The most effective instrument to prevent over-volunteering is considered to be a central internet-based registry of healthy volunteers. Such registries operate in various countries and differ in structure, scope of information collected, types of funding and management. The general operating principles of such registries are described on the example of TOPS data base. TOPS is а special system to prevent over-volunteering that is used by UK phase 1 units. In conclusion, authors urge regulatory authorities and pharmaceutical companies to approach this problem closely because over-volunteering is already a burning issue in our country. It is essential to improve relevant regulatory framework and launch central registries of healthy subjects with regard to international experience.

This article covers important aspect of methodology of clinical trials - source medical documents. Special attention is always paid to source medical records in phase 1 trials when the future of novel medicinal product is at stake. Authors discuss some issues of development and application of trial-specific forms as part of source medical documentation on the basis of practical experience in conducting phase 1 studies on healthy volunteers. Primary focus is on the structure and content of these forms with respect to specific procedures and study population in early phase research. Authors believe that implementation of trial-specific forms improves the quality of clinical trials.

This article discusses the role of pharmacist in early phase clinical trials. Authors emphasize that in Russian phase I units pharmacists are rarely involved in clinical research activities. Probably the lack of regulatory documentation in this field is one of the main reasons. The opposite situation occurs abroad where pharmacist is key member of investigational team. This problem is particularly relevant because number of phase I studies in Russia steadily increases over the last years. Based on their practical experience authors describe the range of pharmacist functions and responsibilities when working in early phase research. Qualification requirements and skills of such specialist are pointed out as well. Due to the fact that not only number of trials but also number of phase I units increases (including private departments) the value of pharmacist in clinical research will grow.

The article describes the results of retrospective epidemiology (non-interventional study) two-stage study. This study was initiated to reveal and analyze changes occurred in the field of detection and modification of cardiovascular risk factors in patients with stable angina over the five-year period. The study identified some positive shifts in how doctors of outpatient cardiology clinic captured information about risk factors in medical records and how they implemented measures of non-pharmacological modification. However, in general degree of physicians’ attention to cardiovascular risk factors remains low.

Aim. To assess five-year trend in terms of specialists’ adherence to guidelines on secondary prevention of cardiovascular diseases in patients with stable angina on the level of out-patient specialized healthcare institution in Moscow.Material and methods. Two-stage retrospective pharmacoepidemiological study was conducted. The object of the study – patient medical records. At the first stage of the study medical records of 2915 patients with stable angina visited the healthcare institution for the first time in 2006 were included, at the second stage – medical records of 1633 patients with stable angina with primary visit in 2011.Results. Over the five-year period prescription rates of drugs improving prognosis in patients with stable angina significantly increased: antiplatelets – up to 82.7%, beta-blockers – up to 74.3%, statins – up to 45.6%. Despite of no changes registered in prescription rate of the ACE inhibitors, marked increase up to 14.7% in prescription rate of angiotensin receptor blockers was revealed. In the prescription structure of pharmacological groups changes were detected concerning the preferred choice of a specific drug. Due to implementation of dual antiplatelet therapy into clinical practice a reduced number of recommendations of acetylsalicylic acid as monotherapy (down to 93.0%) and increased – in combination with clopidogrel (up to 5.4%) was registered at the second stage of the study. Over a five-year period bisoprolol (55.0%) occupied the leading position in the group of beta-blockers. Metoprolol’s prescription rate decreased to 27.4%. Prescription rate of atenolol decreased down to 3.1%, while that of nebivolol increased up to 8.3%. When choosing among statins specialists recommended significantly more often atorvastatin (up to 52.9%). In the group of ACE inhibitors three drugs preserved their leading positions. Meanwhile the number of recommendations of enalapril increased up to 50.8%, perindopril – up to 24.1%. Analysis of prescribed doses revealed significant increase in recommendations of specific drugs in higher daily doses: acetylsalicylic acid 100 mg – up to 71.1%, simvastatin and atorvastatin 20 mg – up to 60.5% and 41.9%, respectively. When prescribing beta-blockers and ACE inhibitors specialists continued to use minimal and medium therapeutic doses, possibly due to dose titration in patients with comorbidities.Conclusion. Study results demonstrated positive trend in terms of specialists’ adherence to guidelines on secondary prevention of cardiovascular diseases in patients with stable angina. However, a number of problem aspects were identified that require further optimization of medical and preventive measures in healthcare institutions.

Aim. To study secondary prevention of cardiovascular diseases among patients of different age groups with a history of myocardial infarction by the example of outpatient cardiology institution.Material and methods. Retrospective pharmacoepidemiological study was conducted by analyzing the medical records of 825 patients with a history of myocardial infarction, who visited the outpatient cardiology institution for the first time in 2011. Patients were divided into two groups according to their age: younger than 60 years (n=308), and 60 years and older (n=517).Results. The population of elderly patients was more severe: significantly more often patients had disability and comorbidities. The prevalence of the main modifiable risk factors could not be assessed fully due to the lack of information in patients’ medical records. Elderly patients were significantly less likely to receive β-blockers (80.3%) and statins (63.8%). No significant differences were found in daily doses of the main prescribed preventive drugs between two groups.Conclusion. Secondary prevention of cardiovascular diseases among patients of different age groups could not be considered proper, as there is low level of attention to the modifiable risk factors and recommendation on their correction. A tendency to under-prescription of angiotensin converting enzyme inhibitors was revealed, as well as significantly lower number of recommendations for taking statins and β-adrenoblockers in the group of elderly patients.

The paper deals with the problem of the interchangeability of brand-name and generic drugs. Touching upon official terminology and the normative documents that govern the registration of generics in Russia and foreign countries, the authors state that there is no concerted approach to estimating drug interchangeability, indicate that there are some disadvantages of using a method for proving the bioequivalence of the compared drugs as evidence for their therapeutic equivalence, and point out that Russia’s legal regulation of drug circulation lacks attention to the proper use of generics. The problem of interchangeability is particularly acute when prescribing narrow therapeutic range drugs, including anticonvulsant drugs. The results of the investigations discussed in the article demonstrate the need for a very cautious approach to using generic drugs in the therapy of epilepsy due to the fact that the disease may worsen. The authors come to the conclusion that treatment with less expensive generic drugs is far from always more economical. The change from a brand-name for a generic drug should be carefully approached, basing on the data of properly designed and conducted studies of therapeutic equivalence.

Aim. To assess 5 years trend in level of doctor’s adherence to actual guidelines on secondary prevention of cardiovascular diseases in patients with a history of myocardial infarction in ambulatory specialized healthcare institution in Moscow. Material and methods. There were 752 patients firstly visited healthcare institution in 2006 and 825 patients – in 2011. Their data was included in two-stage retrospective pharmacoepidemiology study. Results. Prescription rate significantly increased for three of four prophylactic groups recommended for patients with a history of myocardial infarction (antiplatelets – 91.76%, beta-blockers – 83.39%, statins – 69.45%). When assessing prescribed doses of drugs, an increase in a number of their higher doses prescriptions was revealed (at the second stage of the study acetylsalicylic acid 100 mg/day received 75.32% of patients, enalapril 20 mg/day – 30.45%, simvastatin and atorvastatin 20 mg/day – 64.52% and 47.89% of patients, respectively). Conclusion. Results showed growing level of doctor’s adherence to actual recommendations on therapy and secondary prevention of cardiovascular diseases. Nevertheless, the level of adherence remains unsatisfactory and requires additional work with doctors.

Aim. To assess the real clinical practice implementation of the recommendations on secondary cardiovascular disease (CVD) prevention in patients after myocardial infarction (MI).Material and methods. In total, 6,000 ambulatory medical cards were randomly selected from all cards of the patients visited the city cardiology dispanser in 2006. Among the selected cards, 752 belonged to patients with an MI in anamnesis. The information on main CVD risk factors (RFs), achievement of target levels of body mass index (BMI), blood pressure (BP), total cholesterol (TCH), and low-density lipoprotein CH (LDL-CH), as well as the data on pharmaceutical treatment, invasive diagnostics and therapy of coronary heart disease (CHD), were analysed.Results. Inadequate attention of ambulatory specialists to the main modifiable and non-modifiable CVD RFs was observed. The prevalence of achieved target levels of BMI, BP, TCH, and LDL-CH was very low. In post-MI patients, anti-aggregants, statins and anticoagulants as a part of the pharmaceutical secondary CVD prevention, were not administered often enough by the specialists working at polyclinics and the cardiology dispanser. The usage of invasive diagnostics and treatment of CHD remained low.Conclusion. The recommendations on secondary CVD prevention in post-MI patients were implemented inadequately.

Study goal: to assess levels of TNF-α in blood serum of patients with atrial fibrillation during paroxysm and after the episode. To find possible practical application of measuring TNF-α serum levels as a diagnostic method to detect the onset of paroxysm. Methods : 29 patients with IHD and arterial hypertension complicated by rhythm disturbances (paroxysmal atrial fibrillation) were examined. Control group included 33 healthy volunteers. Observation period lasted four weeks. Blood levels of TNF-α were measured during paroxysm with duration up to two days and four weeks after sinus rhythm been restored and remained under control on background of constant anti-anginal, anti-hypertensive and anti-arrhythmic therapy. Results : Direct correlation between the onset time, the severity of paroxysm and the level of serum TNF-α was established. Return to normal levels of TNF-α was observed by the fourth week after restoration of sinus rhythm on background of treatment. In control group TNF-α levels at baseline and four weeks after remained within normal values. Conclusions : Data confirming active involvement of TNF-α in development of inflammation and initiation of apoptosis during paroxysm that results in aggravation of cardiovascular diseases was obtained. Application of the method of assessing TNF-α serum levels as severity and prognostic marker of paroxysmal atrial fibrillation was proposed.

Treatment of hepatitis C is one of the most acute international healthcare problems. High standard in management of patients with HCV virus is combined therapy with pegylated interferon-a plus ribavirin. A necessity to develop new medications and to improve current treatment regiments is determined by high social and economic significance of this disease. Safety and tolerance assessment in healthy volunteers, definition of maximum tolerated dose are conducted in first phase clinical trial of original, Russian medication - pegylated interferon-a, named Algeron (INN - Cepeginterferon alfa-2b). Step by step dose escalation of Algeron in groups of several healthy volunteers was applied in this trial. Results of this trial demonstrated, that safety profile of Algeron has no significant differences with safety profiles of analogical pegylated interferon-a medications. Thus Algeron can be recommended for the second phase clinical trials.

The two-stage retrospective review of 1375 medical records of ambulatory patients with myocardial infarction was carried out in order to assess the delivery rate of up-to-date international and domestic guidelines for secondary CVD prevention over a period of 2001- 2006. The gap between the current guidelines for medicamental prophylaxis and their implementation in clinical outpatient practice was revealed. In spite of the fact that doctors began to prescribe preventive drugs more often target levels for cholesterol and blood pressure were not achieved in the major part of patients with myocardial infarction. The prescription rate of antiaggregants, anticoagulants and statins is still rather low.

Introduction: The publication describes a fragment of the pharmacoepidemiologic study conducted to review the quality of management of patients with stable coronary artery disease (SCAD) in primary care over a 12-year period. The aim of the study was to justify the application of standard operating procedures (SOPs). Such determinants of pharmacotherapy as non-pharmacological modification of cardiovascular risk factors (RFs) and medication adherence were analyzed. Material and methods: A retrospective, cross-sectional, 3-stage (2006, 2011, 2018) study was conducted in a primary care setting of Moscow. As many as 3027, 1834, 805 patients with verified diagnosis of SCAD were included. Demographics, medical history, data on modifiable RFs and prescribed drug therapies were collected. At the third stage, medication adherence was measured, using the 8-item Morisky scale. Results and discussion: Over a 7-year period, better control of modifiable RFs in coronary patients was revealed. The target levels of blood pressure were reached in 58.3% (+20.7%; p < 0.05) of the patients, total cholesterol – in 33.0% (+16.0%; p < 0.05), and low-density lipoprotein cholesterol – in 23.3% (+12.2%; p < 0.05). Two critical problems that determined still inadequate RFs control were identified. The attention of physicians to RFs and rates of non-pharmacological interventions remained low throughout the study. Information on lifestyle RFs was recorded in fewer than one-third of the subjects. The lipid profile was registered only in half of patients’ histories. Non-adherence to pharmacotherapy was identified in 51.3% of patients. Conclusion: Further increase in efficacy of pharmacotherapy might be provided by application of SOPs regarding the registration and correction of modifiable cardiovascular RFs, identification of non-adherent patients and promotion of medication adherence.

Introduction: Lack of research targeting non-adherence to cardiovascular medications in Russia prevents from developing effective interventions to improve adherence. The aim was to study medication adherence in patients with stable coronary artery disease in primary care. Material and methods: The study was conducted in a primary care setting of Moscow. Demography, medical history, pharmacotherapy data were obtained retrospectively from 386 coronary patients’ medical records. Medication adherence was measured by 8-item Morisky Medication Adherence Scale (MMAS-8). A statistical analysis was performed using SPSS Statistics V16.0. Results and discussion: According to the results from MMAS-8, 188 (48.7%) coronary patients had high medication adherence, 135 (35.0%) – moderate, and 63 (16.3%) – low. By the dichotomous interpretation: 48.7% (n = 188) – were adherent, 51.3% (n = 198) – were non-adherent. These groups were similar in gender distribution, age, and medical history profile (p > 0.1 for all variables). Smokers prevailed in the non-adherent group (13.6 vs. 5.3%; p = 0.009). Both groups were equally prescribed beta-blockers, antiplatelets, and statins (p > 0.1 for all). Use of fixed dose combinations (11.7 vs. 5.6%; p = 0.048) and the number of pills taken (mean 5.64 ± 1.52 vs. 5.99 ± 1.62; p = 0.029) were associated with better adherence. Higher values of total cholesterol (mean 5.2 ± 1.4 vs. 4.7 ± 1.2 mmol/L; p < 0.001) and low-density lipoprotein cholesterol (mean 2.9 ± 1.2 vs. 2.4 ± 0.9 mmol/L; p < 0.001) were revealed in non-adherents. Subjects with suboptimal adherence visited general practitioners more frequently (median 5 vs. 3 visits; p = 0,003). Conclusion: Medication non-adherence in coronary outpatients exceeded 50%. High adherence was associated with more frequent use of fixed dose combinations and fewer pills taken by patient. Smoking and poorer control of blood lipids prevailed in non-adherents, who also caused higher load on general practitioners.