Rational Pharmacotherapy in Cardiology

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Vol 15, No 4 (2019)
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450-466 3368

Participants of the study ESSE-RF-2 and co-authors: Moscow: Konstantinov V. V., Pokrovskaya M.S., Efimova I.A., Sivakova O.V.; Krasnodar: Alekseenko S.N., Gubarev S.V.; Оmsk: Livzan M.A., Grishechkina I.A., Rozhkova M.Yu.; Republic of Karelia: Vezikova N.N., Skopec I. S.; Ryazan: Filippov E.V., Dobrynina N.V., Nikulina N.N., Pereverzeva K.G., Moseychuk K.A.

Aim. Evaluate the prevalence, awareness, treatment, and control of hypertension among people aged 25-64 examined in 4 regions of the Russian Federation.

 Material and methods. Study materials were the representative selections of non-organized male (n=3000) and female (n=3714) inhabitants of aged 25-64 from 4 regions of the Russian Federation (Krasnodar region, Omsk region, Ryazan region, the Republic of Karelia), response rate>80%. Systematic stratified multilevel random election was formed with locality criteria (Kisch method). All the participants were interviewed using the standard questionnaire. The universal epidemiological methods and evaluation criteria were used. The study was approved by the local ethics Committee of National research center for preventive medicine. Participants signed informed consent. Hypertension was defined as an average systolic blood pressure (SBP)≥140 mmHg and/or average diastolic blood pressure (DBP)≥90 mmHg and/or antihypertensive therapy (AHT). The efficacy of treatment was the achievement of the target BP. Control group – patients with BP<140/90 mmHg.


Results. Mean SBP and DBP were 128.7±0,3 mmHg and 82.8±0.1 mmHg, respectively, higher BP was detected among male (p<0,001). The prevalence of hypertension was 44.2% that was higher among males than females (49.1% vs 39.9%, р˂0.0005), the highest hypertension frequency was in the Ryazan region. The awareness of hypertension was higher among females than in males 76.8% vs 69.4%. There were more persons with hypertension grade 1 among those, who were not aware of the hypertension. Medications were taken by 65.5% of females and 41.8% of males.

Angiotensin-converting enzyme inhibitors were received by 49.9% of patients, angiotensin II receptor antagonists by 30.9%, beta blockers – 29.5%, diuretics – 22.7%, calcium antagonists – 15.7%, centrally acting drugs – 3.3%, others – 0.2%. The lack of AHT intake was negatively associated with age, ischemic heart disease, urban life and hypo-HDL especially among males. Heart rate >80 per min in females increased by 1.7 times the probability of absence of AHT. The prevalence of effectively treated was 49.7% of the participants with hypertension. The associations between ineffective treatment and abdominal obesity, ischemic heart disease (males), age, rural type of settlement, obesity (females) were found. Only 24.9% of patients had control of the hypertension.

Conclusion. The prevalence of hypertension in Russian Federation remains high. An important task of the medical community is to identify the disease at an earlier stage of its development, before the appearance of complications. This approach can reduce the period from the onset of high blood pressure to a visit to the doctor.

467-477 692

Aim. Since the irrational use of medicine increases the risk of morbidity and mortality in hypertension, this study was aimed to evaluate antihypertensive pharmacotherapy at two districts of Northern Cyprus (NC).

Material and methods. A total of 148 prescriptions including antihypertensive drugs (n=181) were obtained by the aid of five pharmacists between November 2017 August 2018 and evaluated regarding the antihypertensive drug choices and good prescribing principles. The prescribed antihypertensive agents were classified according to the Anatomical Therapeutic Chemical Classification System (ATC) 2, 3 and 5 and the prescriptions were evaluated regarding the availability of format information.

Results. The mean of antihypertensive agents per prescription was 1.2±0.6. According to the ATC-3 subclassification, beta-blockers (22.1%), angiotensin receptor blockers (ARBs) (22.1%), calcium channel blockers (20.4%), angiotensin converting enzyme inhibitor (ACE) inhibitors (17.7%), diuretics (13.8%) and anti-adrenergic drugs (3.9%) were prescribed. According to the ATC-5 subclassification, the most common prescribed antihypertensives were metoprolol (16.6%), amlodipine (16.0%), furosemide (8.8%), captopril (7.7%) and losartan (6.6%). There were no significant relation between the prescribed antihypertensive agents and gender and the physicians serving either in governmental or private hospitals. There were shortcomings in the prescriptions such as age, diagnosis and drug information which were crucial for the chosen of an appropriate antihypertensive agent.

Conclusion. This first pharmacoepidemiological study about antihypertensive drug utilization in NC indicates the imperfections of physicians in terms of prescribing antihypertensive agents according to the guidelines and writing a “legible and good” prescription that contains full information. These findings underline necessity of educational interventions for physicians to disseminate rational use of medicine (RUM) in the NC.

478-483 499

Material and methods. A 32-year prospective cohort follow-up of males from childhood (11-12 years) was carried out. After 32 years of 1005 participants 301 (30.0%) were examined. The survey included: a survey on a standard questionnaire (passport data, the presence of bad habits [smoking, alcohol consumption]), a three-time measurement of blood pressure. The levels of total cholesterol, high and low density lipoprotein cholesterol, triglycerides were determined.

Results. There is no established relationship between the average level of total cholesterol and hypercholesterolemia with smoking status and smoking intensity. It is shown that the level of triglycerides is statistically significantly higher in smokers as compared to non-smokers. Hypertriglyceridemia was not associated with smoking status, but was associated with the smoking index in current smokers, and only with the highest values of this index in past smokers. The probability of being in a group with dyslipidemia was more than 2 times higher in smokers as compared to non-smokers. The differences in the chances of getting into a group with dyslipidemia between smokers and nonsmokers in the past were statistically insignificant. The linear dependence of the frequency of dyslipidemia on the intensity of smoking at the present time, i.e. with increasing intensity of smoking increases the frequency of dyslipidemia. Such a dependence between smoking in the past and the frequency of dyslipidemia was not revealed. The probability of being in a group with a high atherogenic risk is 2 times higher in both smokers at present and smokers in the past as compared to non-smokers. The linear dependence of the frequency of high atherogenic risk on the intensity of smoking both now and in the past is established, i.e. with the increase in the intensity of smoking the frequency of high atherogenic risk increases in both smokers at present and smokers in the past as compared to non-smokers.

Conclusion. Close association of smoking with dyslipidemia was confirmed. The high probability of being in a group with a high atherogenic risk not only in smokers at present, but also smokers in the past indicates the importance of not only secondary, but also primary prevention of smoking.

484-494 663

Aim. To study the nosological spectrum in the syndrome of primary left ventricle hypertrophy (PLVH) using morphological and genetic diagnostics and to compare the clinical course of true hypertrophic cardiomyopathy (HCM) and its phenocopy.

Material and methods. Fifty five adult patients (29 men, 48.2±17.0 years) with PLVH (12 mm and more) were included. The exclusion criteria were athletic heart, hypertensive heart disease, severe valvular disease and other causes of secondary left ventricle (LV) hypertrophy. We performed 11 endomyocardial biopsy, 8 intraoperative biopsy, 1 study of explanted heart, 1 autopsy with virus investigation (real-time polymerase chain reaction) of the blood and myocardium. Mutational screening had included simultaneous sequencing of the MYBPC3, TAZ, TPM1, LDB3, MYL2, ACTC1, MYL3, MYH7, TNNI3 and TNNT2 genes based on NGS technology (Ion Torrent PGMTM) with following Sanger resequencing of potentially significant genetic variants. For patients with a phenotype of particular genetic syndrome the Sanger sequencing of target gene(s) for performed first. Clinical examination had included electrocardiography, Holter monitoring, echocardiography, coronary angiography, computer tomography/magnetic resonance imaging (by indication). The mean follow-up was 8 [3;32] month.

Results. Isolated HCM was found in 28 patients, and 10 have a combination of HCM and noncompaction myocardium (NCM). Mutations in the MYH7 and MYBPC3 genes were detected in six cases. In 17 cases (30.9%) the non-sarcomeric causes of LVHS were detected. Three patients had Fabry disease, 2 ‒ had Danon disease, in 10patients we found amyloidoses, in 1 – Friedreich ataxia, and 1 patient was diagnosed with LEOPARD syndrome (all cases were confirmed by DNA diagnostics). Genotype-positive diagnosis was established in 23.6% of patients. In patients with HCM were significantly more frequent asymmetric septal hypertrophy with obstruction and muscle bridges, in other forms of primary hypertrophy – right ventricular hypertrophy, low QRS voltage, QS complexes and increasing of ejection fraction (EF) (55.7±12.5% vs 62.5±10.1% in HCM, p=0.08). The morphologic signs of myocarditis were in 46.7% of patients with HCM detected: in 3 patients with NCM and in 4 patients with isolated HCM. The viral genome in the myocardium was in 11 patients with HCM (73.3%) detected, previously human herpes virus type 6 (it was correlation with myocarditis) and parvovirus B19. Eleven patients died due to a stroke/heart failure without no significant differences between patients with HCM and phenocopy.

Conclusion. The spectrum of causes of the primary left ventricular hypertrophy is very wide. The frequency of myocarditis associated with sarcomeric HCM was 46.7%. When lower EF and heart failure in patients with HCM can be result of myocarditis, in patients with storage disease they are the result of disease itself.

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Aim. To study the rigidity of the vascular wall and microcirculation parameters in patients with uncontrolled (UCAH) and controlled arterial hypertension (CAH).

Material and methods. 134 patients with essential hypertension were included, among them 88 (65.7%) patients with UCAH and 46 (34.3%) patients with CAH. Patients in both groups were similar by sex, age, duration of hypertension and some biochemical parameters. Patients had a study of the parameters of stiffness of the vascular wall, microcirculation parameters, as well as an evaluate of the plasma level of asymmetric dimethylarginine (ADMA).

Results. Pulse wave velocity (PWV) did not differed between the UCAH and CAH, both in absolute values (1144 [1000-1290] vs 1138 [10281279] cm/sec; p=0.385) and in the frequency of exceeding the normal values (95% vs 92%; p=0.784). Microcirculation index (MI) in CAH was significantly higher than in the UCAH group: 30.55 [27.08-34.4] and 22.82 [18.62-26.05], respectively (p <0.05). ADMA plasma concentration was significantly higher 0.69 [0.62-0.81] μmol/l in UCAH, than in the CAH group 0.62 [0.58-0.70] µmol/l (p <0.05), that shows the presence of endothelial dysfunction. There were detected significant relation between MI and cognitive status.

Conclusion. The results of our study indicate the presence of signs of endothelial dysfunction in patients with UCAH with changes in the stiffness of the vascular wall comparable with the CAH group. This may reflect the slower effect of antihypertensive therapy on the remodeling processes of large vessels in comparison with the microvasculature.

502-509 523

Aim. Examination of knowledge of the basic provisions of clinical guidelines for the management of patients with arterial hypertension and finding out the readiness of doctors for the practical application of updated recommendations

Material and methods. Anonymous questionnaires of 306 doctors served as material for the study. The questionnaire consisted of two parts. The introductory part included questions that allow to find out the specialty, work experience, gender, age, and whether the respondent has cardiovascular risk factors. The main part of the questionnaire included 16 questions regarding provisions of the guidelines on the diagnosis and treatment of arterial hypertension in force at the time of the survey (2017/2018 academic year). Statistical processing of the results was carried out using the Microsoft Excel 2010 software package. Differences were regarded as significant at p<0.05.

Results. The findings suggest that both therapists and cardiologists do not give due importance to the risk stratification of cardiovascular complications in patients with arterial hypertension and are not sufficiently aware of the possibilities and limitations of the use of combinations of antihypertensive drugs. Therapists worse than cardiologists know the main points of the clinical guidelines for the management of patients with arterial hypertension (target blood pressure levels during treatment [64.6% vs 87.7%, p<0.001], indications for combination antihypertensive therapy starting, the possibility of fixed dose combinations using [52.3% vs 83.9%, p<0.001]). A significant part of physicians (both cardiologists and therapists) adequately assess the antihypertensive treatment effectiveness, not enough frequent achievement of the target blood pressure level in their patients and is willing to provide more strict control of blood pressure.

Conclusion. The results of the survey indicate the need of the active education of doctors in the management of patients with arterial hypertension. The most attention should be paid to the training of therapists and general practitioners on the cardiovascular complications risk stratification, the using of the antihypertensive drugs combinations use and methods to increase patient adherence to antihypertensive therapy.


510-517 1351

Аim. To study the efficacy, tolerability and safety of using a fixed dose combination of an ACE inhibitor lisinopril with a prolonged-action diuretic indapamide in patients with degree 1-2 hypertension.

Material and methods. Patients (n = 32) with uncontrolled 1-2 degrees hypertension, moderate or high cardiovascular risk, without severe comorbid diseases, who were prescribed a fixed dose combination of lisinopril (5, 10 or 20 mg) and indapamide (1.5 mg) were included in the observational study. All patients had home monitoring of blood pressure and diuresis, as well as assessment of subjective tolerance of treatment and registration of adverse events within 3 months of observation. Assessment of changes in circadian fluctuations in blood pressure and diuresis, the frequency of achieving the target blood pressure at the outpatient stage, as well as the subjective tolerance of treatment and adverse events during a three-month follow-up.

Results. Target blood pressure was achieved in 44.5% of patients taking the fixed dose combination of lisinopril 5 mg + prolonged-acting indapamide1.5 mg; 76.9% – in patients taking the combination of lisinopril 10 mg + indapamide 1.5 mg; 78,6% – in patients taking the combination of lisinopril 20 mg + indapamide 1.5 mg. The achieved antihypertensive effect was characterized by daily circadian stability, accompanied by an improvement in the initially impaired day and night diuretic profile (increase in the share of daytime diuresis by 29.6% and 22.3% with a decrease in the share of nighttime diuresis by 35% and 49% when using a combination with lisinopril 5 and 10 mg, respectively). The treatment was well tolerated by patients and did not cause the development of serious adverse events. Reported adverse events (non-intense dry cough, headache, general weakness) were transient and did not require correction or withdrawal of treatment.

Conclusion. The fixed dose combination of the ACE inhibitor lisinopril (5, 10 or 20 mg) and the long-acting thiazide-like diuretic indapamide (1.5 mg) had good antihypertensive efficacy with improved circadian blood pressure and diuresis profiles, acceptable tolerance and safety of treatment, as well as a simple choice of doses of the drug components.

518-523 573

Aim. To study detection of atrial septal aneurysm (ASA) by transthoracic echocardiography in patients of the older age group of the therapeutic hospital, as well as combinations with other structural disorders of the heart and blood vessels, as well as other signs of congenital connective tissue dysplasia (CCTD) of other localization.

Material and methods. Identification of ASA as well as other signs of CCTD was performed in patients ≥40 years hospitalized due to exacerbation of therapeutic diseases (n=1119), which had transthoracic echocardiography.

Results. ASA was found in 1.34% of patients (n=15). Undifferentiated connective tissue dysplasia was diagnosed in 14 (93.3%) ASA patients. Prolapse of mitral (60%), tricuspid (33.3%) or both atrio-ventricular valves of the heart (6.7%), patent foramen ovale (33.3%), rudimentary Eustachian valve (6.7%), additional ventricle chords (13.3%), Valsalva sinus dilation (6.7%) was found in ASA patients. 14 (93.3%) patients had electrocardiography signs of cardiac rhythm and conduction disorders. Chronic venous insufficiency (100%), disorders of the musculoskeletal system (100%), hiatal hernia (40%), anterior abdominal wall hernia (46.7%), nephroptosis (46.7%), kidney cysts (33.3%) intestinal diverticula and dolichosigma (26.7%), bronchiectasis (6.7%) were also found.

Conclusion. ASA was found in 1.34% of patients in a therapeutic hospital ≥40 years. Clinically significant and prognostically unfavorable CCTDs were not found in ASA patients in this study. However, physicians should consider the possibility of the presence of other abnormalities of the heart and large vessels, as well as other systems and organs that can lead to fatal events, in these patients.

524-529 555

The clinical, instrumental and molecular-genetic studies for proband and family members for identification of family form of left ventricular noncompaction cardiomyopathy (LVNC) presented in the article. According to the results of the examination, the diagnosis LVNC was made. Drug therapy was adjusted, and a cardioverter defibrillator was implanted for the primary prevention of sudden cardiac death. Given the hereditary nature of the disease, family screening was conducted. By the family screening the disease was diagnosed in the mother of proband. Later, was made exome sequencing in a group of genes related to the development of left ventricular noncompaction cardiomyopathy. One likely pathogenic variant (rs1471414348, stop codon) in the TTN gene was detected. The discovered variant was validated by Sanger sequencing and was detected only in the proband and his mother, and was absent in other relatives. There were no other pathogenic and probably pathogenic variants in genes associated with the development of left ventricular noncompaction and other cardiomyopathies. As a result of family screening the new cases were diagnosed, the pathogenic variant of the TTN gene was identified, that is probably responsible for the development of the LVNC phenotype.


530-537 666

The purpose of this review is to examine the possibilities and prospects for the use of direct oral anticoagulants for the prevention of thromboembolic complications in patients with atrial fibrillation and chronic kidney disease. Chronic kidney disease is an independent risk factor for cardiovascular complications. Atrial fibrillation is associated with a higher risk of developing chronic kidney disease and more rapid progression of existing renal pathology. The presence of chronic kidney disease in atrial fibrillation on the one hand leads to an increased risk of thromboembolism, and on the other to an increased risk of bleeding when using anticoagulants. The standard for the prevention of thromboembolic complications in atrial fibrillation, including those with concomitant renal pathology, was considered warfarin for many years. However, modern studies have shown that the use of warfarin may enhance vascular calcification in patients with chronic kidney disease, which in turn may lead to an increased risk of ischemic strokes.

Analyzing clinical recommendations, randomized studies, meta-analyzes and a systematic review on the use of anticoagulants in patients with atrial fibrillation and renal pathology, revealed the advantage of using direct oral anticoagulants over warfarin at stage 1-3 of chronic kidney disease. Data on the use of direct oral anticoagulants with a more pronounced renal dysfunction and in patients on dialysis is limited due to the lack of a sufficient number of large randomized studies. Due to the presence of renal clearance in all oral anticoagulants, their pharmacokinetics changes to some extent with a decrease in the glomerular filtration rate, which requires dose adjustment of drugs depending on creatinine clearance. Therefore, the use of anticoagulants for the prevention of thromboembolic complications during atrial fibrillation requires special attention in patients with chronic kidney disease.


538-545 766

Aim. To evaluate an incidence of oral anticoagulants (OAC) administration during longterm follow-up period in patients with atrial fibrillation (AF) enrolled in outpatient and hospital RECVASA registries.

Material and methods. 3169 patients with AF were enrolled in outpatient registries RECVASA (Ryazan), RECVASA AF-Yaroslavl and hospital registries RECVASA AF (Moscow, Kursk, Tula), age 70.9±10.7 years, 43.1% men. The incidence of OAC administration was evaluated in hospital and outpatient settings, including longterm follow-up period (2-6 years).

Results. OAC were administrated only in 42.2% of cases (1335 from 3169 patients; age 69.1±10.4 years, 43% men), including warfarin (817 patients; 26%) and non-vitamin K antagonist oral anticoagulants (NOAC) – 518 (16%). Patients with permanent and persistant types of AF had lower incidence of OAC administration (43% and 40%) than in cases of paroxysmal type (47.6%, p<0.05), despite of the higher СНА2DS2-VASc risk score (4.69±1.66 and 4.23±1.57 vs 3.81±1.69; р<0.05). Patients with and without history of stroke received OAC in 42.5% and 40% of cases that means no significant difference (p>0.05) contrary to the pronounced difference of thromboembolic risk in these groups (6.14±1.34 and 3.77±1.39; р<0.001). The incidence of OAC administration in hospitals (54.1%) was 2.3 times higher than before hospitalization (23.8%) and was 4.1 times higher than in outpatient registries (13.5%). During follow-up period after hospital treatment (2.3±0.9 years) this parameter decreased from 54.1% to 41.2%, but was still 1.8 times higher than before admission to the hospital. After 4 years follow-up in RECVASA (Ryazan) registry we revealed 4.4 times higher incidence of OAC administration compared with enrollment data (4.2% and 18.3%, р<0.0001). This data was confirmed by the information from outpatient medical cards of accidentally generated group (75 from 297 patients survived during follow-up period): 5.3% at baseline and 22.7% six years later.

Conclusions. RECVASA registries in 5 regions of Russia revealed low incidence of OAC administration. The risk of thromboembolic events was higher in patients with AF and no OAC administration compared with patients who received OAC. Patients with paroxysmal type of AF received OAC more often than those with permanent type. There were no significant differences of incidence of OAC therapy in patients with and without history of stroke. Both questioning of patients with AF and analysis of medical cards in outpatient clinics revealed higher incidence of OAC administration after 4-6 years of follow-up compared with the stage of enrollment in registries.


546-552 555

Aim. To describe the design of TRUST study (Influence of Participation in Randomized Controlled Trials on adheRence to Medicines' Intake and regUlar viSits to the docTor) and present the first part of this study to determine the motives of patient participation in clinical trials.

Material and methods. The main group of TRUST study included patients of the outpatient registrar PROFILE, which were taking part in one or more international randomized clinical trials, conducted from 2011 to 2018. The standard registration card of PROFILE register was used to assess the clinical and demographic data of patients.

In 2019 full-time/telephone contact with patients was established, during which, based on the original questionnaire, the motives of the participation in trials, their attitude towards randomized controlled trials (RCT), and their adherence to monitoring in medical institutions were determined. This publication presents the results of the first part of the study.

Results. 102 patients were enrolled in the study, telephone /personal contact was established for 88 patients, the life status of 9 of them by 2019 was defined as "dead", 77 were interviewed, 2 – refused to answer. Over 80% of patients completed participation in RCTs more than one year ago. 71.6% of patients participated in more than one RCT. In 60% of cases, patients claimed that this was the proposal of the doctor of the scientific center. For 79% of patients, RCTs had the opportunity to access highly skilled medical care. Only 18% of patients indicated that they received the necessary qualified medical care before entering the study. In cases where patients answered dichotomous questions (such as "yes"/"no"), the overwhelming majority of patients (74%) claimed that it was the authority of the doctor of the scientific center and the fear of losing the possibility of further observation became the main reason for participating in RCTs.

Conclusion. In the first part of the TRUST study, it was revealed that in Russia the main reason of participation in RCT is the recommendation of a doctor from a specialized scientific center.


553-557 676

The article discusses issues related to the prescription of anticoagulant therapy to elderly patients with atrial fibrillation (AF), especially those over 70 and 80 years of age. The relevance of the issue is primarily due to the prevalence of AF in this cohort of patients, and the second is due to the higher incidence of comorbidity. The presented material demonstrates the peculiarities of anticoagulant therapy application in groups of patients older than 75, based on the data of randomized clinical trials, and also presents extrapolation of the results of RCTs to the real clinical practice (data of registers and cohort trials). The use of unreasonably low doses of oral anticoagulants in elderly patients is debated. It often leads to a decrease in the efficacy of anticoagulant therapy without improving the drugs safety profile. A new validated scale (ABH) for evaluating of anticoagulant therapy safety is presented in the article. The ABH scale can be used before prescribing to patients exactly direct oral anticoagulants. This scale is simpler and more practical than the HAS-BLED scale. The data for the ABH scale are validated based on direct oral anticoagulants in 21,248 patients from the Norwegian register. The presented results demonstrate a favorable efficiency and safety profile of rivaroxaban in comparison with warfarin in patients 75 years and older. Thus, the overall benefit for the use of rivaroxaban against warfarin in patients > 75 years of age in the subanalysis of the ROCKET-AF study was statistically significantly greater than in younger patients with AF. Data on 11121 patients with AF who were treated with rivaroxaban for the prevention of stroke and systemic embolism are included in the combined analysis of the XANTUS, XANAP and XANTUS-EL registers. 96% of patients in the study did not have serious thromboembolic events. The amount of major bleeding was 1.7 per 100 patient-years, and gastrointestinal bleeding was 0.7 per 100 patient-years. This turned out to be less than in some other registry studies. In addition, patients showed good adherence to rivaroxaban treatment: after a year, 77.4% of patients continued to take the drug.

558-567 1004

The most important result of the revision of the European and Russian guidelines for the management of arterial hypertension (AH) was a special focus on initializing antihypertensive treatment with single-pill combinations (SPCs) in majority patients with AH. Combination of the angiotensin II receptor blocker and thiazide diuretic is one of the possible first line SPCs in the absence of specific clinical conditions according to the new guidelines. In this regard, SPC of telmisartan and hydrochlorothiazide (HCT), worth special noticing in the classes of sartans and thiazide diuretics, since both drugs have a long clinical experience and large body of evidence of antihypertensive efficacy and safety, as well as telmisartan also has a number of superior target-organ protective and metabolic properties distinguishing it from other members of the class. In real clinical practice TANDEM study telmisartan and its SPC with HCT showed high antihypertensive efficacy and good tolerability in patients with all AH grades and with isolated systolic AH and allowed to achieve target blood pressure levels in the most of patients. Long-lasting effect is another essential characteristic of telmisartan, this feature allows to control blood pressure throughout the day, including the morning surge, which is the most “dangerous” in terms of cardiovascular risk. Telmisartan also provide powerful target-organ protection realized at the level of all AH target-organs. Finally, another unique pharmacological property of telmisartan and its combination with HCT is a favourable effect on the carbohydrate and lipid profile, which comprises of increasing tissue sensitivity to insulin, normalizing blood glucose levels, reducing blood total cholesterol, low-density lipoprotein cholesterol and triglycerides and thereby reducing risk of atherosclerosis development and progression. Telmisartan/HCT SPC should be recommended for wide use in hypertensive patients to control blood pressure, protect end-organs, improve prognosis and reduce cardiovascular risk due to its high antihypertensive efficacy, the ability to provide the large target-organ protection and a beneficial metabolic effect.

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The review presents the important problem of resistant hypertension. Its real prevalence is unknown. According to population studies and metaanalyzes of clinical studies, the prevalence of this most severe form of hypertension reaches 12-15% in the general population and 15-18% in clinical cohorts. Over the past decades, an increase in its frequency among patients with hypertension has been noted. Based on the results of large-scale studies, risk factors are detected that allow to assess the risk for the resistance to antihypertensive drugs. Adherence to ongoing antihypertensive therapy is crucial to addressing the issue of hypertension resistance; there are acceptable ways to evaluate it in clinical practice. The review discusses the most common mistakes in the choice of therapy, which can cause resistance to antihypertensive treatment, namely irrational drug combinations, insufficient dosage of the drug, and the use of non-prolonged forms of drugs. The latest recommendations for the diagnosis and treatment of hypertension, including its resistant form, are analyzed. The review contains a rationale based on the results of randomized clinical trials, the choice antihypertensive strategy in this variant of arterial hypertension. The importance of fixed combination antihypertensive drugs, as well as thiazine-like diuretics and amlodipine is stressed. The results of studies demonstrate the rational for the use of antimineralcorticoid drugs, namely spironolactone, for this category of patients. The authors offer an updated algorithm for the diagnosis and treatment of resistant hypertension, based on the sections of the latest clinical recommendations on this problem.

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The scientific basis of the selection algorithms for the management of patients with hypertension and hypercholesterolemia is presented in article. The advantages and limitations of current recommendations on the management of patients with hypercholesterolemia, which were presented by American and European experts, are discussed. Data on the narrow-mindedness of use of risk assessment scales for the development of cardiovascular complications for primary prevention in a wide population are presented. The question of the ratio of proven facts and expert opinions in clinical recommendations, as well as the validity of a flexible approach to the choice of tactics for a specific patient, considering the most acceptable approaches presented in different clinical recommendations, is being considered. The validity of recommendations for achieving lower concentrations of lowdensity lipoprotein cholesterol in patients with high and very high cardiovascular risk is discussed. The difficult problem of choosing target blood pressure levels in patients with hypertension and with some characteristics or concomitant diseases and/or risk factors is discussed. The evidence base of modern drugs for preventing the development of cardiovascular complications and/or treating patients with such complications is discussed, including new data on the benefits of longer treatment with atorvastatin for the primary prevention of cardiovascular complications in patients with hypertension are discussed. Data on the problems of the choice of drugs used for the primary or secondary prevention of cardiovascular complications in patients with hypertension and hypercholesterolemia are presented.

586-592 900

The frequency of infective endocarditis (IE) has increased 3 times over the past 30 years. The incidence of IE morbidity is recorded in all countries of the world and in the Russian Federation more than 40 people per 1 million population get sick. One of the most frequent causative agents of infective endocarditis is Enterococcus faecalis (E. faecalis), which takes the third place in the structure of the frequency of IE pathogens. Enterococcal IE remains a disease with high mortality, despite the emergence of new groups of antibacterial drugs. This review includes the results of studies of the efficacy and safety of various antimicrobial regimens of IE caused by E. faecalis. The analysis of data from foreign and native studies of antimicrobial treatment in patients with infective endocarditis, accompanied by enterococcal bacteremia is presented in the review. The search for literature performed by using medical databases: MEDLINE, EMBASE, eLIBRARY. The current review included studies of the efficacy and safety of antimicrobial treatment. The main antibiotic therapy regimens of IE caused by E. faecalis include 2 beta-lactam antibiotics or a combination of ampicillin and gentamicin, according to the results of 5 found studies. Found antimicrobial regimens significantly did not affect mortality. Data from international registries testify to the efficacy and safety of daptomycin monotherapy for enterococcal endocarditis. Linezolid and daptomycin are the main drugs of treating infective endocarditis caused by vancomycin-resistant enterococci. Native studies report of a high level of resistance of enterococcal strains to beta-lactam antibacterial drugs. The duration of fever, the frequency of surgical heart valves interventions, the duration of bacteremia are not fully represented in each of the studies, and it is difficult to evaluate these factors. Ampicillin+ceftriaxone and ampicillin+gentamicin are the main antimicrobial treatment regimens of enterococcal endocarditis. Efficacy of these regimens is not significantly different. Treatment of IE should be carried out taking into the epidemiological situation and the strain resistance.


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In recent years, there has been a persistent trend towards the more frequent prescription of direct oral anticoagulants (DOACs) compared with vitamin K antagonists due to the extensive body of evidence showing their high safety and efficacy, which in some cases exceed those of warfarin, and also by reason of there is no necessity for regular monitoring of international normalized ratio. However, the question of the reasonable and rational prescription of DOACs becomes relevant, including issues of their dosing, especially as a result of increasing in the number of patients with a complex cardiovascular risk profile and multimorbidity. In these terms, apixaban stands high among the DOAC class, and its high efficacy and safety both in full dose and reasonably reduced dosage has been proved, including older patients, patients with chronic kidney disease, coronary artery disease, with history of acute coronary syndrome and individuals undergoing percutaneous coronary intervention. This DOAC has strict indications to reduce the dose, they are specified in the drug label, and in such cases a reduced dose should be prescribed, in these clinical conditions the effectiveness and safety of apixaban is also proven. The favorable apixaban pharmacokinetic properties, consisting in low renal clearance, lack of clinically relevant interaction with food and the linear smooth effect on the blood coagulation components without episodes of hypo- and hypercoagulation, are the most important components of high efficacy and safety of this DOAC. The optimal efficacy and safety coupling of apixaban is reflected in the exclusively high patients’ adherence to the treatment confirmed by evidence-based medicine data, and therefore there is no necessity for additional procedures to maintain adherence. All the aforementioned facts allow us to recommend apixaban for widespread use in patients requiring anticoagulant therapy for optimal prevention of systemic thromboembolism and minimizing the associated risk of bleeding.


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