Rational Pharmacotherapy in Cardiology

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Vol 12, No 1 (2016)
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4-15 1142

Aim. To study a pattern of concomitant cardiovascular diseases (CVDs) and to estimate particularities and quality of medical antihypertensive therapy in hypertensive patients in real outpatient practice with a help of the Registry in Ryazan region.

Material and methods. A total of 3690 patients with hypertension, ischemic heart disease, chronic heart failure and atrial fibrillation, who had attended general practitioners and cardiologists of 3 outpatient clinics in Ryazan city, were enrolled in the outpatient Registry of cardiovascular diseases (RECVASA). The diagnosis of hypertension was recorded in 3648 of 3690 (98.9%) outpatient charts, 28.1% of the subjects were men and 71.9% - women.

Results. A total of 2907 (79.7%) of 3648 patients had combination of hypertension with other CVDs. Combination of 3-4 cardiovascular diagnoses was registered in 63.8% of the cases. 11.5% and 9.5% of the patients had a history of myocardial infarction and cerebral stroke, respectively. Diagnosis of hypertension was verified in 448 of 450 randomized hypertensive patients (99.6%). The incidence of prescription of one and two antihypertensive drugs (AHDs) was 25% and 39%, respectively, of 3 AHDs – 21%, 4 and more – 2%. AHDs were not prescribed in 13% of hypertensive patients. The mean number of prescribed AHDs was 1.73. The mean incidence rate of target blood pressure achievement was 26.1%. We have noted insufficient ACE inhibitors/angiotensin receptor blockers (ARB) and beta-blockers prescription in different concomitant CVDs. Patients with 3-4 cardiovascular diagnoses were more often prescribed combined antihypertensive treatment. Prescription of ACE inhibitors/ARB, beta-blockers and thiazide diuretics combination was preferable in 74.1% of the cases, when taking into account absolute and relative contraindications for betablockers use – in 64.0%. 15.2% of the hypertensive patients used reimbursed drugs for CVDs at the moment of the Registry enrollment as compared with 39.2% in previous years (p<0.05).

Conclusion. The RECVASA study data allowed revealing high incidence of concomitant CVDs in hypertensive patients, insufficient use of combined antihypertensive treatment, including AHDs with proved favorable influence on prognosis. Achievement of concordance of medical treatment to national and international guidelines, taking into account concomitant CVDs, and optimization of patients’ coverage with reimbursed drugs are the main reserves for antihypertensive treatment quality improvement.

16-20 708

Aim. To study the efficacy and safety of generic orlistat in comparison with the original drug in obese patients.

Material and methods. Patients with obesity degree 1-3 (n=60; 11.7% men and 88.3% women) were included into the open comparative randomized controlled study in parallel groups. After randomization 40 patients received of generic orlistat and 20 – the original orlistat. The duration of follow-up was 12 weeks. Changes in body weight, body mass index, and waist circumference were assessed, as well as the proportion of patients with a weight loss of 5-10% or more from baseline.

Results. Weight loss >5% was observed in 28 and 25% of patients in the groups of generic and original orlistat, respectively, and weight loss >10% - in 7.7% of patients only in the group of generic drug. No significant changes in blood pressure and heart rate were found. A significant reduction in total cholesterol and low density lipoprotein cholesterol was revealed. 11 (27.5%) adverse events were observed in the group of generic orlistat and 5 (25%) – in the group of original orlistat.

Conclusion. Generic orlistat 120 mg in capsules showed clinical equivalence to the original drug. Safety and tolerability of treatment with both drugs were comparable.

21-25 655

Aim. To evaluate the effect of 12 weeks of complex therapy with the fixed combination of enalapril and indapamide on indicators of vascular stiffness of large arteries and parameters of skin microcirculation (MC) in patients with arterial hypertension (HT) and diabetes mellitus (DM) type 2.

Material and methods. 30 patients with HT stage II-III in combination with DM type 2 aged 40-70 years were included into the study. The fixed combination of enalapril and indapamide in addition to lipid-lowering and hypoglycemic therapy was prescribed to all patients. Elastic properties of large arteries were assessed by analyzing the pulse wave velocity (PWV) and the calculation of the index of aortic stiffness (IAS). Skin MC and level of glycated hemoglobin (HbA1c) were also determined.

Results. After the 12-week treatment all patients reached the target values of blood pressure (BP). Office systolic and diastolic BP levels decreased by 18.8 and 13.1% (p<0.05 for both), respectively. The treatment did not have a negative effect on glucose metabolism – HbA1C concentration decreased by 2.7%. PWV in the vessels of elastic and muscular types decreased by 10.8 and 10.1% (p<0.05 for both), respectively, and IAS decreased by 27.4% (p<0.05). Significant growth in factor myogenic regulation of MC and reduction in bypass indicator by 21.8% were found.

Conclusion. Combined therapy with the inclusion of a fixed combination of enalapril and indapamide for 12 weeks had a high antihypertensive efficacy and good tolerability in patients with HT and DM type 2. Treatment significantly reduced the vascular stiffness of large arteries and improved the MC indices in these patients.

26-30 531

Aim. To study the relationships between clinical and functional features of chronic obstructive pulmonary disease (COPD) and status of cardiovascular system with focus on identifying factors associated with the atrial fibrillation (AF) in patients with COPD.

Material and methods. Patients (n=94) with COPD out of exacerbation and airways obstruction of 2-4 degree (GOLD 2013) were examined. The spirometry, daily pulse oximetry, 24-hour ECG and blood pressure monitoring with vascular wall stiffness estimation, echocardiography were performed. Levels of high-sensitivity C-reactive protein (CRP) were
also assessed.

Results. AF paroxysms were found in 46 patients, including newly diagnosed ones in 22 patients. According to the results of multiple correlation analysis, the frequency of AF paroxysms correlated with forced expiratory volume in 1 sec (FEV1) (R=-0.348; p=0.013), minimum oxygen saturation of the blood (min%SpO2) (R=-0.356; p=0.011), CRP level (R=0.442; p=0.001), the sizes of both atria (p<0.001), isovolumic relaxation time (IVRT) of left ventricle (LV) (R=0.350; p=0.022), the right ventricle (RV) size (R=0.478; p<0.001), systolic blood pressure level in the pulmonary artery (PASP) (р<0.001), vascular stiffness - pulse wave velocity in aorta (PWao) (p=0.001). The influence of FEV1 on the left atrium volume index (χ2=7.0; p=0.008) and IVRT LV (χ2=7.9; p=0.005) was revealed. Correlations between min%SpO2 and IVRT and PWao were observed.

Conclusion. Severe bronchial obstruction, hypoxemia, systemic inflammation with increase in vascular stiffness (PWao) and myocardium remodeling (increase in the sizes of both atria, PASP, RV size and diastolic dysfunction of LV) are the factors that associated with the occurrence of AF in patients with COPD.

31-39 574

Aim. Analysis of the efficacy and safety of the new oral anticoagulants (NOACs) in the management of venous thromboembolism (VTE).

Material and methods. This meta-analysis of randomized controlled trials (RCTs) was made in accordance with the instructions “Preferred reporting items for systematic reviews and meta-analyses (PRISMA)”.

Results. The meta-analysis included 5 RCTs. NOACs were as effective as vitamin K antagonists (VKAs) in preventing recurrent symptomatic VTE (RR=0.93; 95% CI 0.77-1.12; p=0.44). The incidence of recurrent thrombosis (RR=0.82; 95% CI 0.63-1.08; p=0.16) and deep vein thrombosis ± fatal or nonfatal pulmonary embolism (RR=1.06; 95% CI 0.81-1.40; p=0.66) was comparable in the groups of comparison. Meta-analysis of the safety of the NOACs suggested significant reduction of risk of major bleeding as compared with standard therapy (RR=0.54; 95% CI 0.42-0.69; р<0.00001). The incidence of all types of bleeding was significantly lower with NOACs (RR=0.70; 95% CI 0.51-0.95; p=0.02). All-cause mortality rate was comparable between the groups (RR=0.93; 95% CI 0.76-1.13; p=0.46).

Conclusions. NOACs are as effective as the standard therapy, at that they are much safer in VTE treatment.


45-50 545

Aim. To study the incidence and structure of sudden cardiac death (SCD) among the working population of the Bryansk region, as well as to determine its share in the structure of total and cardiovascular mortality in this age group.

Material and methods. We analyzed the structure and incidence of SCD in 417740 people of working age (25-64 years) in five major areas of the Bryansk region and the city of Bryansk in 2012. Medical records (outpatient card, patient’s chart, autopsy protocol, a medical certificate of death) of 1447 people of working age who died from diseases of the circulatory system were analyzed.

Results. 106 cases corresponded to the criteria for SCD, which determined the frequency of SCD 25.4 per 100000 working-age population. The predominance of men over women (85% vs 15%) was marked. Only 24% of cases of SCD occurred in hospitals, while 76% - in outpatient settings. A strong association between SCD and age was noted. Chronic (43%) and acute (37%) forms of ischemic heart disease turned out to be the main clinical entities that caused SCD.

Conclusion. The share of SCD in total and cardiovascular mortality was 2.9% and 7.3% respectively. Strong correlation between SCD rate and age was found. Chronic and acute forms of ischemic heart disease turned out to be the main clinical entities that caused SCD.

51-55 465

Aim. To evaluate the long-term prognosis of life in patients after cerebral stroke (MI) and to identify the main factors influencing it.

Material and methods. All patients (n=960) who had MI or transient ischemic attack in the period from 01.01.2009 to 31.12.2011, admitted to Lyubertsy district hospital №2, were included into the register of LIS-2. The primary endpoint was total mortality of patients.

Results. The average age of patients was 72±9 years, 2/3 were women. 207 patients (21.7%) died in the hospital, 753 were discharged from the hospital. Median follow-up was 2.8 (2.1, 3.5) years. 31.5% of the patients died during this period. The main cause of death (36%) was re-MI, and 22.4% of patients died from the heart failure. The relative risk (RR) of death was significantly increased with the age of patients (RR=1.1). The probability of death increased in the presence of diabetes mellitus (RR=1.4), alcohol abuse (RR=2.3), any signs of consciousness disorders in the acute phase of MI (RR=1.6), heart failure (RR=1.6), atrial fibrillation (RR=1.4). Patients who were treated with calcium channel blockers before admission to the hospital, had a lower risk of death than those who did not receive these drugs (RR=0.4). Prescription of ACE inhibitors at discharge from the hospital reduced significantly the risk of death in the long-term period (RR=0.7).

Conclusion. High rate of long-term mortality in the LIS-2 register can be largely explained by the poor quality of primary and secondary prevention of cardiovascular events.



56-62 565

Aim. To assess clinical and medical history data of patients with acute myocardial infarction (AMI) admitted to the hospital with a possibility of primary percutaneous coronary intervention (PCI), according to the AMI Register in Khabarovsk.

Material and methods. The AMI Register includes data on all patients consecutively admitted to the Khabarovsk Regional Vascular Center from 01.01.2014 till 31.03.2014. 321 AMI patients were included into the study.

Result. 177 patients with ST-segment elevation AMI (55.14%) were enrolled into the Register as well as 135 patients with non-ST-segment elevation AMI (42.05%) and 9 patients with early recurrent myocardial infarction and early postinfarction stenocardia (2.8%). 54.19% of patients with a reference AMI admitted to the vascular center in the first 6 hours, and 65.39% of patients – in the first 12 hours. The systemic thrombolysis was carried out in 20 patients (6.2%). PCI with coronary stenting was carried out successfully in 122 patients (68.92%) with ST-segment elevation AMI and in 25 (18.5%) patients with non-ST elevation AMI. The average hospital stay was 8.6 days and total mortality – 9% (n=29).

Conclusion. The present treatment of AMI patients (modern pharmacotherapy, primary PCI) is associated with a low lethality. The late admitting of patients and as a result – admitting of 29.59% of AMI-patients in a day after AMI onset is a point for the improvement of AMI management as well as low rate of the interhospital transfers (4.36%).

63-65 1373

One of the most common tests for evaluating of medication adherence – 4-question scale Moriscos-Green – is considered. Advantages (flexibility, conciseness) and disadvantages (insufficient sensitivity and specificity) of this test are presented. Disadvantages of 4-question version of the test were considered by the authors in development a new version of the scale (8-question) to assess medication adherence. The latest version of the Moriscos test has a high sensitivity in a fairly good specificity. The versatility of the new version of the test is confirmed by the studies. Preference in the use of this test is shown for screening assessment of medication adherence in patients with various chronic diseases. Besides the use of 8-question Moriscos scale is proved as a reference in the development and validation of new questionnaires on adherence to therapy.


66-71 630

The last decade is marked by the significant reinterpretation of the gut microbiota contribution to chronic disease progression. The researchers’ careful attention is focused on improving the understanding of the metabolic pathways of two dietary compounds – choline and L-carnitine, which stand at the origins of trimethylamine N-oxide (TMAO) formation. This small molecule of great expectations has gained an impressive appreciation due to its ability to promote atherogenesis, and thus increasing the risk of major adverse cardiovascular events and affecting patients’ prognosis. This paper aims to discuss updated concept of microbiota-dependent cardiometabolic consequences of consumption of food rich in quaternary amines as well as to touch upon the currently existing interventions in TMAO production, their limitations and future scientific directions.


72-78 632

Renal dysfunction in patients with acute coronary syndrome complicates the diagnosis, worsens the short- and long-term prognosis, reduces the effectiveness of the reperfusion therapy, and increases the risk of bleeding. It is important to aim for treatment based on the evidence-based studies and according to the updated guidelines of the professional associations.

79-86 561

Indications and efficacy of drugs used for the treatment of pulmonary hypertension are considered. Stages of the treatment of pulmonary arterial hypertension are discussed, including maintenance therapy, specific therapy with calcium channel blockers, prostacyclin analogues, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, prostacyclin agonists, guanylate cyclase stimulators, combination treatment.

87-93 628

Recent scientific data on the influence of magnesium on the cardiovascular and reproductive system in women is summarized. Evidence-based medicine data has shown a link between magnesium blood (plasma, red blood cells) levels and increased risk of somatic diseases in women of reproductive age. Hypomagnesemia increases the risk of sudden cardiac death, unstable angina, and cardiovascular mortality due to myocardial tissue functional disorders, mitochondrial failure. Magnesium ions are essential for maintaining the physiological pregnancy. Experimental and clinical data allows using drugs of magnesium in preventing and treating heart disease in women. Their use is also possible for treatment of gynecological diseases, for pregnant women with arterial hypertension and connective tissue dysplasia.


94-100 659

Features of pharmacotherapy in the elderly patients are discussed. Data on the pharmacokinetics and pharmacodynamics, comorbidity, polypragmasy and treatment adherence among patients of this age group are presented.

101-105 7825

Currently there are no generally accepted guidelines for the use of rivaroxaban together with amiodarone, verapamil or diltiazem in patients with creatinine clearance (CrCl)<80 ml/min. Some researchers suggest that in renal failure amiodarone, verapamil and diltiazem contribute to a significant increase in plasma concentrations of rivaroxaban that is accompanied by increased risk of bleeding. According to preliminary calculations, it seems rational to reduce the dose of rivaroxaban when co-administered with these drugs: to 15 mg/day in patients with ClCr 50-79 ml/min and to 10 mg/day in patients with ClCr<50 ml/min.



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