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Rational Pharmacotherapy in Cardiology

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Vol 17, No 5 (2021)
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ORIGINAL STUDIES 

668-673 108
Abstract

Aim. We aimed to assess safety and effectiveness of class III antiarrhythmic drug Refralon for conversion of atrial fibrillation (AFib) and flutter (AFl) in post-registration trial and to compare data of primary center (National medical research center in cardiology) with data of other hospitals.

Material and Methods. We performed retrospective cohort study in 727 patients (451 enrolled in primary center and 276 enrolled in other hospitals) admitted between June 24, 2014 and June 24, 2019. Refralon was administered for conversion of AFib and AFl in intense care units in escalating doses (10-30 micrograms/kg) intravenously.

Results. Conversion of AFib and AFl into sinus rhythm was achieved in 53,6% after administration of 10 mcg/kg dose, in 73% after administration of 20 mcg/kg dose and in 91,6% after administration of Refralon in dose up to 30 mcg/kg. No mortality and no major adverse cardiac events registered in our study. Asystole >3.0 sec observed in 5% (35 of 727) of patients): in 5% (24 of 451) of patients enrolled in primary center and in 4% (11 of 276) of patients enrolled in other hospitals; 95% confidence interval (CI) [-0.09; 0.113]. Asystole> 5.0 s observed in 1.7% of patients who further required non-urgent implantation of a permanent pacemaker due to manifestations of sinus node dysfunction. Cardiac conduction disturbances (exclusively sinus bradycardia) were registered in 7% (53 of 727) patients: in 8% (37 of 451) of patients enrolled in primary center and in 6% (17 of 276) of patients enrolled in other hospitals; 95% CI: [-0.1; 0.15]. Only 0.14% of patients had symptomatic sinus bradycardia that resolved after atropine injection. Ventricular arrhythmias (exclusively Torsade de pointes tachycardia in excessive QT interval prolongation) were registered in 1.7% (12 of 727) patients: in 2% (9 of 451) of patients in primary center and in 1% (3 of 276) of patients of other hospitals; 95% CI: [-0.06; 0.08]. QTc interval prolongation to values >500 ms documented in 19% (138 of 727) of patients: in 21% (95 of 451) of patients in primary center and in 16% (43 of 276) of patients in other hospitals; 95% CI: [-0.13; 0.24].

Conclusion: In post-registration multicenter trial Refralon demonstrated good safety profile in conversion of AFib and AFl. Potential risk of TdP tachycardia mandates precautions with the use of the drug. In other hospitals Refralon did not demonstrate lower safety than in primary medical center.

674-682 130
Abstract

Aim. To study the relationship between the level of haptoglobin and the main indicators of microcirculation (MC) in patients with different phenotypes of chronic heart failure (CHF).

Materials and methods. Patients with different phenotypes of functional class II-IV chronic heart failure according to NYHA (n=80) underwent a general clinical examination, determination of the serum haptoglobin level by enzyme-linked immunosorbent assay, as well as an assessment of the MC state on the medial surface of the upper third of the leg by laser Doppler flowmetry (LDF).

Results. Patients with CHF included patients with preserved left ventricular ejection fraction (HFpEF; n=27, intermediate ejection fraction (HFmrEF; n=25) and reduced ejection fraction (HFrEF; n=28). The median value of haptoglobin in the HFpEF group was 1387.6 [ 747.5; 1946.9] mg/l, in the HFmrEF group was 1583.4 [818.9; 2201.4] mg/l, in the HFrEF group was 968.5 [509.5; 1324.4] mg/l. Correlation analysis revealed statistically significant relationships between haptoglobin and the amplitudes of the endothelial frequency range (Ae) in the groups of HFmrEF (r=-0.628, 95% confidence interval [CI] -0.256; -0.825, p=0.003) and HFrEF (r=-0.503, 95% CI -0.089; -0.803, p=0.02). A negative relationship between the haptoglobin level and Kv and σ was revealed, as well as a formula for calculating the value of haptoglobin was obtained, which is predicted on the basis of the amplitude index of the endothelial frequency range: [haptoglobin]=1787-(4053×Ae).

Conclusion. The multifactorial effect of haptoglobin is realized in the central and peripheral mechanisms of MC regulation. Low values of haptoglobin in blood plasma should be considered as a potential marker for the development of complications and used in a comprehensive assessment of the state of patients with CHF. Evaluation of the diagnostic and prognostic significance of haptoglobin, especially in patients with HFmrEF, requires further study.

683-687 129
Abstract

Aim. Study the effect of a study video, which was created by researchers and devoted to the atherosclerosis development and the effect of statin therapy on atherosclerotic plaque, on adherence to long-term therapy in patients with high or very high risk of cardiovascular complications.

Material and methods. 120 patients admitted to hospital with cardiovascular diseases were included in the study. Patients were randomized into 2 groups: in the main group (n=60), the information video edited by the researchers was shown to patients on the eve of discharge, in addition to a printed brochure on lifestyle and diet modification, and in the control group (n=60), patients were given only a standard brochure. The motivating video shows the damage to the cardiovascular system by the atherosclerotic process and the beneficial effect on the body of constant intake of statins. After 1 and 3 months after discharge from the hospital, telephone calls were made, after which the patients had to visit the center for an objective examination by a researcher and control of laboratory parameters. After 1 month, 110 patients visited the center, after 3 months, 98 respondents visited the center.

Results. The group with the information video demonstration noted more frequent adherence to medical recommendations compared to the control: after 1 month, 52 (96%) patients continued treatment versus 48 (86%) patients, 3 months after discharge 48 (96%) patients continued treatment versus 38 (79%) patients (p<0.05). After 1 month, 38 (70%) patients in the intervention group continued taking statins versus 29 (43%) respondents in the control group (p<0.05), 3 months after discharge, 40 (80%) patients in the intervention group continued to take statins versus 33 (69%) control patients (p<0.09).

Conclusion. Demonstration of a motivating video about the effect of statins on the atherosclerosis course increases patient adherence to medicinal therapy, including adherence to statins.

688-695 92
Abstract

Purpose. To study approaches to the quantitative assessment of breast arterial calcification (BAC) – a new surrogate marker of high cardiovascular risk in women, to determine the most detailed way to quantify BAC and to assess the reproducibility of these parameters.

Material and methods. Mammograms of 1,078 women were analyzed for the presence of BAC. The intraoperator reproducibility of the assessment of the severity of BAC using a 12-point scale (Margolies L et al., 2016) was studied by analyzing 20 mammograms by the same operator twice with an interval of at least 2 weeks. Inter-operator reproducibility was studied by analyzing 99 mammograms by two independent operators.

Results. When assessing the intraoperative reproducibility of the total score for each mammary gland, the exact coincidence of the results was noted in 70% (95% confidence interval [CI] 53.5-83.4), in cases of difference of no more than 1 point – in 27.5% (95%CI 14.6-43.9), only in 1 case the difference in assessments was 2 points. No systematic error was found between the two measurements (p=1.0), the correlation coefficient was rs=0.973. The assessment of inter-operator reproducibility showed that the exact coincidence of indicators was present in 48.5% (95%CI 41.3-55.7), in 91.4% (95% CI 86.6-94.9) cases, the total score for each the mammary gland differed by no more than 1 point. There was no systematic error between the measurements of the two experts (p=0.438), the correlation coefficient was rs=0.942.

Conclusion. A good intraoperator and interoperator reproducibility of indicators of the severity of BAC on a 12-point scale has been shown, which makes it possible to recommend it for use in science and practice.

696-701 90
Abstract

Aim. To study the possibilities and limitations of the social network as a digital medical tool, which is aimed at improving programs for primary and secondary stroke prevention in young people.

Material and methods. The study was carried out in the format of online training for volunteers. At the first stage of the work, the online school “Stroke in Young People” was announced in 8 medical blogs. As part of the school, a special account was created for readers (n=1354). At the second stage, 49 respondents (4% of men, whose average age was 24.4±5.2 years) were selected from 1354 listeners, who were surveyed on “Awareness of risk factors and stroke symptoms among users of social networks” before and after the online school.

Results. The online school audience is predominantly female (91%), and 43% of readers were in the 25-34 age group. The total number of people who listened to and read the online school material is 8712 people. 17% worked in the healthcare system, and 22% of respondents had a history of stroke. 38 (78%) people of the 2nd stage among the respondents independently searched for information about stroke earlier, and 30 (61%) received this information passively from medical workers in 2020. Before the online school start, the majority of respondents (over 60%) were aware of 2 out of 7 stroke risk factors (dyslipidemia and arterial hypertension) and 3 out of 6 stroke signs (drooping of the face half, weakness in the limbs and difficulty speaking). Less than 40% of the participants considered the stroke risk factors for diabetes mellitus, other cardiovascular diseases (CVD), obesity, and alcohol use; less than 20% were aware of stroke symptoms such as impaired vision and coordination and very severe headache. After completing online learning, the greatest increase in knowledge was found among the following risk factors – smoking and other CVDs (p<0.05); stroke symptoms - headache and drooping of the face half (p<0.05).

Conclusion. The online school aroused interest among healthcare workers and people without medical education, including those with stroke. Most of the respondents believed that they knew how to prevent a stroke (over 80%) and would be able to provide first aid to a person with a stroke (over 90%). At the same time, the awareness of risk factors and stroke symptoms was low prior to the start of learning, even though the study included healthcare workers and stroke survivors. Online learning has led to increased awareness of some risk factors and stroke symptoms. Social media can be one of the tools for medical prevention of stroke in young people, but program planning should take into account the way the material is presented and its readability.

702-711 71
Abstract

Aim. Assess the structure of comorbid conditions, cardiovascular pharmacotherapy and outcomes in patients with atrial fibrillation (AF) and concomitant coronary artery disease (CAD) included in the outpatient and hospital RECVASA registries.

Materials and methods. 3169 patients with AF were enrolled in outpatient RECVASA (Ryazan), RECVASA AF-Yaroslavl registries and hospital RECVASA AF (Moscow, Kursk, Tula). 2497 (78.8%) registries of patients with AF had CAD and 703 (28.2%) of them had a previous myocardial infarction (MI).

Results. There were 2,497 patients with a combination of AF and CAD (age was 72.2±9.9 years; 43.1% of men; CHA2DS2-VASc – 4.57±1.61 points; HAS-BLED – 1.60±0,75 points), and the group with AF without CAD included 672 patients (age was 66.0±12.3 years; 43.2% of men; CHA2DS2-VASc – 3.26±1.67 points; HAS-BLED – 1,11±0.74 points). Patients with CAD were on average 6.2 years older and had a higher risk of thromboembolic and hemorrhagic complications (p<0.05). 703 patients with a combination of AF and CAD had the previous myocardial infarction (MI; age was 72.3±9.5 years; 55.2% of men; CHA2DS2-VASc – 4.57±1.61; HAS-BLED – 1.65±0.76), and 1794 patients didn't have previous MI (age was 72.2±10.0 years; 38.4% of men; CHA2DS2-VASc – 4.30±1.50; HAS-BLED – 1.58±0.78). The proportion of men was 1.4 times higher among those with the previous MI. Patients with a combination of AF and CAD significantly more often (p <0.0001) than in the absence of CAD received a diagnosis of hypertension (93.8% and 78.6%), chronic heart failure (90.1% and 51.2%), diabetes mellitus (21.4% and 13.8%), chronic kidney disease (24.8% and 17.7%), as well as anemia (7.0% and 3.0%; p=0.001). Patients with and without the previous MI had the only significant difference in the form of a diabetes mellitus higher incidence having the previous MI (27% versus 19.2%, p=0.0008). The frequency of proper cardiovascular pharmacotherapy was insufficient, mainly in the presence of CAD (67.8%) than in its absence (74.5%), especially the prescription of anticoagulants (39.1% and 66.2%; p <0.0001), as well as in the presence of the previous MI (63.3%) than in its absence (74.3%). The presence of CAD and, in particular, the previous MI, was significantly associated with a higher risk of death (risk ratio [RR]=1.58; 95% confidence interval [CI] was 1.33-1.88; p <0.001 and RR=1.59; 95% CI was 1.33-1.90; p <0.001), as well as with a higher risk of developing a combined cardiovascular endpoint (RR=1.88; 95% CI was 1.17-3 , 00; p <0.001 and RR=1.75; 95% CI was 1.44-2.12; p<0.001, respectively).

Conclusion. 78.8% of patients from AF registries in 5 regions of Russia were diagnosed with CAD, of which 28.2% had previously suffered myocardial infarction. Patients with a combination of AF and CAD more often than in the absence of CAD had hypertension, chronic heart failure, diabetes, chronic kidney disease and anemia. Patients with the previous MI had higher incidence of diabetes than those without the previous MI. The frequency of proper cardiovascular pharmacotherapy was insufficient, and to a greater extent in the presence of CAD and the previous MI than in their absence. All-cause mortality was recorded in patients with a combination of AF and CAD more often than in the absence of CAD. All-cause mortality and the incidence of nonfatal myocardial infarction were higher in patients with AF and the previous MI than in those without the previous MI. The presence of CAD and, in particular, the previous MI, was significantly associated with a higher risk of death, as well as a higher risk of developing a combined cardiovascular endpoint.

712-718 97
Abstract

Aim. To study in healthy individuals the gender and age characteristics of left ventricular (LV) myocardial work indicators, their correlations with global LV deformity indicators and echocardiographic parameters characterizing LV systolic and diastolic functions.

Materials and methods. 70 Healthy individuals (n=70; 34 men and 36 women; aged 39.3±8.9 years) were included in the study. The echocardiographic examination determined the standard parameters and indicators of myocardial work: global work efficiency (GWE), global constructive work (GCW), global wasted work (GWW), global myocardial work index (GWI); as well as the myocardium deformation characteristics: global longitudinal deformation (GLS), global radial deformation (GRS) and global circular deformation (GCS). Spearman's correlation coefficient was used to investigate the relationship between parameters. A correlation was considered weak at r≤0.3, moderate at 0.3<r<0.7, and strong at r≥0.7.

Results. The average value of global work efficiency (GWE) in men was 97% (96; 98), in women – 98% (97; 98). Global constructive work (GCW) in men was 2343.8±350.4 mm Hg%, in women – 2362.2±343.8 mm Hg%. The average value of global wasted work (GWW) in men was 46 mm Hg% (27; 75), in women – 44 mm Hg% (33; 55.5). The global myocardial work index (GWI) in men was 2069.9±356.4 mm Hg%, in women – 2055.7±339.9 mm Hg%. No significant differences were found in the comparative analysis of performance indicators. The analysis of correlations found that the myocardial work indicators didn't have significant correlations with age. Ejection fraction was moderately correlated with GWI (r=0.45) and GCW (r=0.49). Global longitudinal strain was strongly correlated with GWI (r=0.77) and GCW (r=0.77). Global radial strain correlated moderately directly with GWI (r=0.4) and GCW (r=0.4). Global circular strain was moderately correlated with GCW (r=0.35). A strong negative correlation was found between the GWE indicator and the post systolic contraction index (PSI) (r=-0.85). At the same time, PSI and GWW had a strong positive correlation (r=0.85).

Conclusion. Indicators of LV myocardial work in healthy individuals do not have gender differences. The efficiency of the work of the myocardium depends primarily on the deformation of the LV, while the constructive work is determined by the volume characteristics. The wasted work indicator depends on the number of segments that peak in the post-systolic period.

NOTES FROM PRACTICE 

719-723 103
Abstract

Aim. Evaluation of the effect of polymorphisms of the CYP2D6, CYP2C8 genes on the efficacy and safety of postoperative analgesia with ketoprofen in patients with coronary artery disease after cardiac surgery.

Material and methods. The study included 90 patients with an established diagnosis of coronary artery disease and postoperative period after cardiac surgery. Patients received ketoprofen 100 mg intramuscularly 2 times a day for 5 days. The intensity of pain was rated by Numeric Rating Scale. The severity of dyspepsia was assessed by the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. DNA was isolated from venous blood using an automated system. Single nucleotide polymorphisms CYP2C8 (C>T) rs11572080, CYP2D6*4 (1846G>A) rs3892097 were determined by the real-time polymerase chain reaction method.

Results. In patients with genotypes GA and GG for the allelic variant CYP2D6*4, significant differences in the intensity of pain syndrome were found on days 4 and 5 of the postoperative period: 3,91±2,17 and 4,95±1,8 points (p=0,04), 3,52±1,95 and 4,5±1,7 points (p=0,04) in patients with GA and GG genotypes on days 4 and 5, respectively. In patients with the CT genotype for the CYP2C8 rs11572080, the severity of dyspepsia by GSRS was significantly higher than in patients with the CC genotype: 22,67±7,64 and 18,97±4,25 points, respectively.

Conclusion. Patients with the GA genotype for the CYP2D6*4 allelic variant showed a lower intensity of pain syndrome than the GG genotype. In patients with the CT genotype for the CYP2C8 rs11572080, higher dyspepsia was revealed than in the CC genotype.

724-728 110
Abstract

Aim. Compare the incidence of the left atrial appendage (LAA) thrombus dissolution in patients with persistent nonvalvular atrial fibrillation receiving warfarin and direct oral anticoagulants (DOAC).

Materials and methods. 68 patients with persistent nonvalvular atrial fibrillation were included in a retrospective study (age was 59.7±9.8 years, 60.3% men), in whom at least one repeated transesophageal echocardiographic examination was performed after detecting a thrombus. After detecting a thrombus in the LAA, 37 (54.4%) patients started or continued taking warfarin in doses that ensure the INR maintenance at the level of 2-3, 14 (20.6%) started or continued taking dabigatran at a dose of 150 mg 2 times/day, 14 (20.6%) started or continued taking rivaroxaban 20 mg 1 time/day and 3 (4.4%) started or continued taking apixaban 5 mg 2 times/day. Repeated transesophageal echocardiographic examination was performed on average 33.3±14.2 days after the first one.

Results. Dissolution of a previously identified thrombus was found in 26 (83.9%) of 31 patients receiving DOAC and in 19 (51.4%) of 37 patients receiving warfarin (p=0.011). The logistic regression analysis showed that the chances of a thrombus dissolution in LAA while taking DOAC are 14.8 times (95% confidence interval [CI] was 2.469-88.72) higher than while taking warfarin. The size and the rate at which blood is expelled from the LAA also have an independent influence on the chances of thrombus dissolution. An increase in the size of a thrombus by 1 mm reduces the chances of a thrombus dissolution by 1.136 (95% CI was 1.040-1.244) times, and an increase in the rate of blood expulsion from the LAA by 1 cm/sec increases these chances by 1.105 (95% CI was 1.003-1.219) times.

Conclusion. In the present study, the incidence of the LAA thrombus dissolution in patients with persistent nonvalvular atrial fibrillation while receiving DOAC was higher than while receiving warfarin.

729-737 63
Abstract

Aim. To study the late results of medical and interventional treatment in patients with morphologically verified nature of idiopathic arrhythmias.

Methods. The prospective study included 20 patients (mean age 43.1±11.3 years, 10 female) with atrial fibrillation (AF), supraventricular and ventricular extrasystole, supraventricular and ventricular tachycardia, conduction disturbance without structural heart changes. In addition to the standard examination, the level of anti-heart antibodies was initially determined; endomyocardial biopsy (EMB) of the right ventricle with PCR study for the viral genome; DNA diagnostics (n=4), coronary angioraphy (n=6), skin biopsy (n=1) were performed. The median follow-up was 134 [128; 138] months.

Results. By EMB in the initial examination were diagnosed: active (n=8)/borderline (n=3) infectious immune myocarditis; parvovirus-positive endomyocarditis (n=1); undifferentiated vasculitis (n=2); myocardial vasculitis (n=1); Fabry disease (n=1); arrhythmogenic right ventricular dysplasia (n=1); unspecified cardiomyopathy (n=2). Anti-heart antibodies were the most important in myocarditis diagnosis and monitoring. All patients with myocarditis/vasculitis (n=15) received its basic therapy: acyclovir (n=10); immunoglobulin G 10-12.5 g (n=2); hydroxychloroquine 200 mg/day (n=15); glucocorticoids (n=14); azathioprine 150 mg/day (n=2). The late results were evaluated in all patients with myocarditis. Initially, in 62.5% of patients a resistance of AF to all antiarrhythmic drugs was noted. After treatment the average frequency of AF paroxysms decreased (from 8 [5; 8] to 3 [1,25; 7,75] points). By the end of the follow-up, six patients underwent radiofrequency ablation (RFA) for AF, the full effect was achieved once. All patients without RFA have AF partially or completely resistant to drugs. Two patients (without RFA) died from ischemic stroke/ pulmonary embolism.

Conclusion. Using EMB the causes of idiopathic arrhythmias (mainly AF) were diagnosed: immune inflammatory diseases in 75% and genetic in 25% of patients. As a result of complex treatment, the general burden of arrhythmias has decreased. But the presence of myocarditis and primary cardiomyopathy, without reducing the cardiac contractility and dilatation, does not allow achieving a stable antiarrhythmic effect. Lethality for 11 years was 10%. The causes of death were thromboembolic complications.

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY 

738-742 80
Abstract

Aim. Assess the medical therapy quality in patients with chronic heart failure (CHF) and patients' adherence to the treatment depending on the previous observation in a specialized medical center as part of an of an outpatient registry.

Materials and methods. An analysis of the medical therapy quality in patients with CHF was carried out as part of the COMPLIANCE prospective observational study (NCT04262583). 72 patients with CHF verified according to the protocol were included in the study. The average age of the patients was 69.1±9.5 years (31% of women and 69% of men). Patients were divided into groups: those who first applied to a specialized department during the period of the study inclusion, or those who were previously observed in a specialized department. The general adherence assessment to medical therapy was carried out using the original questionnaire «The adherence scale of the National Society for Evidence-Based Pharmacotherapy» which was supplemented with questions to assess the actual adherence to specific medical drugs recommended for patients with CHF.

Results. According to the results of the study, beta-blockers were prescribed to 70 (97.2%) patients. Angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs) were recommended in 68 (94%) patients. Mineralocorticoid receptor antagonists were included in therapy in 6 out of 9 patients who were shown to be prescribed (66.6%). The choice of medical drugs within the group was not always adequate. For example, ACEi/ARBs with proven efficacy in patients with CHF were prescribed only in 72% of patients. Comparative analysis of adherence to medical therapy between patients of the selected groups demonstrated a higher adherence to the recommended therapy in patients who were previously observed in a specialized center.

Conclusion. The medical therapy quality for patients with CHF doesn't always comply with current clinical guidelines. The choice of a medical drug within a group is not always adequate. Regular observation in a specialized center contributes to a higher adherence to the recommended therapy.

POINT OF VIEW 

743-751 78
Abstract

Obesity is a multifactorial disease that leads to excessive adipose tissue accumulation, mainly visceral fat. Importance and prevalence of obesity has increased significantly in recent decades all over the world. Until now, the pandemic of obesity has been associated more to lifestyle changes: excessive eating and low physical activity. In recent years, special attention has been paid to studying of composition and functions of intestinal microbiota as major factor in development of obesity and related comorbidities, such as hypertension, cardiac ischemia, heart failure and others. It is proved that gut microbiota affects extraction, accumulation and consumption of energy derived from food, lipid metabolism and immune response. It is also revealed that composition of the microbiota is different in thin and obese people. Thus, study of the relationship between intestinal microbiota composition and risk factors for cardiovascular diseases, in particular obesity, is an actual task. The purpose of this review is analyzing of literature about assessment of relationship between composition and functions of intestinal microbiota in the diagnostics, prevention and treatment of obesity and cardiovascular diseases.

752-760 71
Abstract

Beta-adrenergic blockers are a valuable class of cardiovascular drugs and are widely used in the treatment of arterial hypertension (AH), coronary heart disease, chronic heart failure (CHF), cardiac arrhythmias, significantly improving the prognosis of patients. However, the clinical efficacy of betablockers is largely dependent on the genetic polymorphism of beta1-adrenergic receptors (ADRB1). The aim of the review was a systematic analysis of scientific data from pharmacogenetic studies on the role of beta1-adrenergic receptor polymorphism in the clinical efficacy of beta-blockers in the treatment of hypertension, chronic heart failure, and atrial fibrillation. The results of clinical trials and meta-analyzes were used. Of greatest importance is the genetic polymorphism of beta1-adrenergic receptors of two loci – Arg389Gly and Ser49Gly; the frequency of occurrence of variant and less functionally active alleles Gly389 and Gly49 in Europeans reaches 27% and 15%. The variant Gly389 allele has reduced functional activity and carriers have a weak response to the use of beta-blockers. In carriers of variant alleles Gly389 and Gly49 a reduced hypotensive effect on the use of beta-blockers was observed, and in studies of long-term efficacy, carriage of variant alleles was accompanied by an increase in the frequency and risk of unfavorable outcomes of hypertension. In pharmacogenetic studies, a reduced effect of the effect on myocardial remodeling in patients with CHF for beta-blockers in carriers of the variant Gly389 allele were confirmed. According to two meta-analyzes of trials on use of beta-blockers in patients with CHF, the frequency of increased left ventricle ejection fraction was significantly higher in carriers of the wild Arg389Arg gene type (risk ratio=1.83, p=0,001). In contrast, in atrial fibrillation, the frequency of rhythm control with beta-blockers was achieved better in the presence of the variant allele Gly389 with “loss of function”. Another polymorphic Gly49 allele plays a role in desensitization and down-regulation of beta1-receptor activity, although clinically this effect has been less obvious and contradictory. However, in studies, a more pronounced clinical effect of beta-blockers was observed in carriers of the wild genotype Ser49Ser, as well as in carriers of the haplotype Ser49Ser/Arg389Arg. Thus, genetic polymorphism ADRB1 may be another important predictor of the effectiveness of beta-blockers in clinical practice, which must be taken into account in the treatment of cardiovascular diseases.

761-770 59
Abstract

Coronary revascularization is one of the most studied types of interventions in cardiology, but there is no consensus among specialists about the indications for its implementation in patients with chronic coronary syndromes (CCS). The data of recently completed clinical trials on the role of revascularization in CCS clearly contradict the current Guidelines, emphasizing the high effectiveness of modern conservative therapy. This paper discusses the main recommendations of the most significant American and European Guidelines on myocardial revascularization, and also analyzes the appropriateness of revascularization to improve the prognosis and symptoms in chronic coronary syndromes in view of the new research data, primarily the ISCHEMIA study (NCT01471522). Its strengths and limitations are discussed in detail. The data on the expediency of revacularization in CCS, obtained after the completion of ISCHEMIA and its potential significance, as well as subgroup analyses of ISCHEMIA, including in the most important ‘problem’ subgroups (3-vessel disease, proximal LAD disease, severe ischemia on stress test, etc.) are discussed. The paper also discusses the important achievements in modern drug therapy of chronic coronary syndromes, primarily antithrombotic therapy. The data of the COMPASS study (NCT01776424) are discussed, based on which the addition of a second antithrombotic drug – rivaroxaban in a small dose (2.5 mg BID) – is recommended for patients with CCS without atrial fibrillation who have high-risk characteristics. Indications the administration of dual antithrombotic therapy to patients with CCS, comparative results of its various regimens in relation to the prevention of cardiovascular complications, the risk of bleeding and the net clinical effect are given.

CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY 

771-778 64
Abstract

Oral anticoagulant therapy is widely used in different patients for the prevention and treatment of thromboembolic events: in atrial fibrillation, deep vein thrombosis/pulmonary embolism, acute coronary syndrome, in the early postoperative period after orthopedic surgery. Nowadays it is possible to use vitamin K antagonists (warfarin) as well as direct oral anticoagulants (DOAC): dabigatran, rivaroxaban, apixaban and edoxaban. The mai complication of any anticoagulant therapy is bleeding (gastrointestinal, intracranial, etc.), which seriously limits its usage. In this review the incidence of gastrointestinal bleeding (GIB) associated with oral anticoagulants intake was analyzed according to the results of both large randomized and postregistration trials. Furthermore, the effect of age on the risk of GIB development is discussed, and also aspects of the pathophysiology of gastrointestinal mucosa lesions in patients taking DOAC are considered.

779-784 77
Abstract

More than 50 years after Propranolol was introduced to the pharmaceutical market as a drug that can lower the heart rate, beta-blockers (BAB) are still widely used in the pharmacotherapy of cardiovascular diseases. However, the use of BAB has a number of limitations, first of all, due to adverse drug events (AE) that develop during their use. The purpose of our review was to study the features of the BAB AE manifested by injuries of the skin and its appendages. The clinical manifestations of them are the development or exacerbation of psoriasis, lichen planus, contact dermatitis, acrocyanosis, Raynaud's disease, alopecia, hyperhidrosis, vitiligo, anaphylaxis, and allergic skin reactions. True medicinal psoriasis occurs in patients taking BAB with no family or previous history and most often mimics erythrodermic psoriasis and palmar-plantar pustular psoriasis. Systemic use of BAB can also be accompanied by exacerbation of vitiligo. In patients with segmental vitiligo, the results of Doppler flowmetry and iontophoresis showed increased blood flow in vitiligo foci compared with normal skin. The development of anaphylactic reactions against the background of BAB therapy may be due to the modulation of adenylate cyclase, which can affect the release of anaphylactogenic mediators, as well as a decrease in the severity of cardiovascular compensatory changes. The peculiarities of the development of such reactions may be the resistance of patients to traditional treatment, which is due to the development of paradoxical reflex vagotonic effects when using adrenaline. Some of the mentioned AE may pose a potential threat to the life and health of the patient and therefore require additional discussion.

785-791 13880
Abstract

The aim of this article is to represent the characterization of the clinical case of chemotherapy-related atrial fibrillation (AF) development in the young woman, elaborated as a result of multiple neoadjuvant and adjuvant modes of the intake of chemotherapy (both anthracycline based and non-anthracycline ones). In this case, the noted disturbances of heart rhythm should be recognized as a manifestation of cardiotoxicity. The latter implies the degree of detrimental effect of chemotherapeutical medication on the morphophynctional parameters of the cardiovascular system. Anthracycline drugs, being highly effective chemotherapytical agents, provide well-known toxic effects on the heart and vessels. Anthracycline mediated cardiotoxicity is a well- known veracity that dates back to the 60s of the last century, but up to now this medication sustains irreplaceable components of big volume of chemotherapy modes. Moreover, it should be noted that relatively newer drugs also posses certain cardiotoxicogenic potential.

OUR MENTORS 

792-798 96
Abstract

September, 2021 marks the 175th anniversary of the opening of the Faculty Therapeutic Clinic (FTC) of the Imperial Moscow University, which is a successor of the First (1805) and Second (1820) Clinical Institutes with their therapeutic beds and chairs, and thus is the oldest therapeutic clinic in Russia. From 1930 the Clinic became part of the newly formed I.M. Sechenov First Moscow Medical Institute (now Sechenov University) and retains continuity to the present day. This publication is one of three research articles prepared by the staff of the Clinic for the anniversary and devoted to little-known pages of biography and scientific activities of the three heads of the FTC at the crucial stages of its history – A.I. Over, G.A. Zakharyin and the last prerevolutionary director – N.F. Golubov.

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)