Rational Pharmacotherapy in Cardiology

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Vol 16, No 2 (2020)
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166-174 830

In the context of the increased incidence of infectious endocarditis (IE) in the elderly, an assessment of clinical features of IE in elderly patients is still controversial.

Aim. To study the clinical features and outcomes of IE in patients aged ≥65 years.

Material and methods. А comparative assessment of risk factors, etiology, clinical manifestations, outcomes was performed in 75 IE patients ≥65 years old and in 356 IE patients <65 years old.

Results. In patients ≥65 years old IE was more often associated with previous medical care (odds ratio [OR]=14.9; 95% confidence interval [95%CI] 8.6;25.9), infections and tumors of the genitourinary system or tumors of the gastrointestinal tract (OR=12.6; 95%CI 6.4;24.6); there were more concomitant oncological diseases (OR=66.2; 95%CI 19.3;226.8), diabetes mellitus (OR=9.9; 95%CI 4.5;22.1), chronic kidney disease (OR=27.0; 95%CI 13.6;53.3). In patients ≥65 years old compared with non-drug users IE patients <65 years old (n=266), the incidence of enterococcal IE was higher (OR=3.3; 95%CI 1.4;7.9); the timing of IE diagnosis was longer – 60 (37;152) vs 30 (20;110) days (p<0.05); cardiac surgery was performed less often (8% vs 24.8%; p<0.05); in-hospital mortality was almost two-fold higher. However, with the exclusion from the mortality rate assessment of postmortem diagnosed IE cases in-hospital mortality in patients ≥65 years old and patients <65 years old did not differ significantly (14.8% vs 12.2% in non-drug users <65 years old and 14.9% in drug-users IE).

Conclusion. Late diagnosis of IE and comorbidity, which limits the possibility of cardiac surgery, are the most important prognostic unfavorable features of IE in the elderly.

175-190 984

Aim. To evaluate the effectiveness and safety of telmisartan, used in monotherapy or in combination with hydrochlorothiazide or amlodipine, in real clinical practice in patients with diagnosed arterial hypertension who have not reached the target levels of blood pressure (BP).

Material and methods. The study was a non-intervention, prospective, multicenter, comparative, observational, epidemiological program, which was carried out in Russian medical institutions. The total patient population in which the prescribed therapy was administered included 1933 people (758 men and 1175 women, mean age 57.0-59.3 years). Participants were followed-up for 12 weeks. The change in office BP was evaluated on the 4th and 12th week.

Results. Significant (p<0.001 in all cases) change in office BP compared with the initial data were recorded in all study groups of therapy already at 4 weeks of treatment and became even more pronounced at 12 weeks. In the telmisartan monotherapy group, BP decreased from 155.7±10.7/92.2±7.6 mm Hg to 131.4±12.1/80.8±7.3 mm Hg at the end of the 4th week and to 125.3±7.6/78.2±6.1 mm Hg – at the end of the 12th week. Similarly, after treatment with the combination of telmisartan and hydrochlorothiazide, BP decreased from 162.7±12.6/94.3±7.9 mm Hg to 133.2±12.5/81.6±8.4 mmHg at the end of the 4th week and to 126.0±7.8/78.4±6.7 mm Hg – at the end of the 12th week. In telmisartan/amlodipine group, a decrease in BP also occurred, from 162.5±13.2/94.6±8.6 mm Hg to 132.8±14.5/81.3±7.5 mm Hg on the 4th week and to 125.4±8.7/78.4±5.6 mm Hg at the end of follow up (12 weeks). The proportion of patients who reached the target BP (<140/90 mm Hg) after treatment with telmisartan as monotherapy was 91.7%, after treatment with telmisartan+hydrochlorothiazide – 89.6%, after treatment with telmisartan+amlodipine – 92.8%. Throughout the program, prescribed therapy was well tolerated by patients. During the study, 47 adverse events (AEs) were recorded in 36 patients: 31 AEs with telmisartan monotherapy, 5 AEs with telmisartan/hydrochlorothiazide combination, and 11 AEs with telmisartan/amlodipine combination. Most of the AEs registered during the trial resolved by the end of the study, in four cases the date of AEs resolve is unknown, in two cases, at the time of completion of the study, AEs continued.

Conclusion. In the TAINA study a high antihypertensive efficacy and a comparable favorable safety and tolerability profile of telmisartan, used as monotherapy and in combination with hydrochlorothiazide or amlodipine was determined.

191-198 492

Aim. To study nicorandil prescription effects before elective percutaneous coronary intervention (PCI) to prevent myocardial injury and 4a type acute myocardial infarction (MI, primary endpoint) and cardiovascular events (CVE) in the first year after PCI (secondary endpoint) in patients with stable coronary artery disease.

Material and methods. 182 patients with stable coronary artery disease were included into the study and were randomized into two groups: nicorandil treatment group (n=90) and a control group with a standard medical treatment (n=92). Nicorandil was prescribed orally: 2 days before PCI – 30 mg/day; on the day of PCI – 20 mg 2 hours before intervention and 10 mg 6-12 hours after PCI; over the next 30 days – 30 mg/day. High sensitivity troponin I (hs-Tr) and creatine kinase-MB tests were carried out before PCI, 24 and 72 hours after the intervention; the 4a type MI was diagnosed according to the 4th Universal Definition. Non-fatal myocardial infarction, nonfatal stroke, death from cardiovascular diseases, repeat revascularization (PCI, coronary artery bypass surgery due to aggravation), hospital admissions for angina pectoris recurrence (without interventions) and death from any causes were considered as cardiovascular events. Data on adverse outcomes were collected over the hospital stay, and then 30, 180 and 365 days after the hospital discharge.

Results. 4a type MI was diagnosed in 14 patients (8%), in women – 12% and in men – 6%. There was a significant decrease in the incidence of type 4a MI in the nicorandil group (n=3; 3%) compared with the control group (n=11; 12%; p=0.05). Secondary endpoint was recorded in 21% of patients. The relationship was found between 4a type MI and the incidence of CVE the next year after the PCI (p=0.01). In patients with type 4a MI CVE odd ratio increases 5.8 times with confidence interval from 1.5426 to 21.6024. According to the logistic regression analysis the significant relationship between hs-Tr growth 24 hours after the PCI and CVE incidence next year after the PCI was found with cutting value 389.8 pg/ml, AUC=0.641 (p=0.04).

Сonclusion. Peroral nicorandil 30 mg/day 2 days before PCI, 20 mg 2 hours before surgery and 10 mg 6-12 hours after PCI, and 30 mg/day next 30 days after PCI decreases the risk of intraoperative myocardial injury and CVE in the next year after PCI.

199-205 598

Aim. To evaluate the effectiveness of the anticoagulant choice algorithm in the prevention of complications of atrial fibrillation (AF).

Material and methods. Patients with AF (n=98) were included into observational prospective study. The level of adherence to treatment, risk of food interactions and presence of CYP2C9 and VKORC1 genes mutations were determined at the initial examination. These indicators were necessary to specify an eligible anticoagulant according to the evaluated algorithm. Therapy was prescribed by the attending physician. Hemorrhagic and thromboembolic complications were assessed at the next examination after 24 weeks.

Results. Hemorrhagic complications were observed in 31.6% of patients during the follow-up. Their number was comparable in individuals taking antiplatelet agents and direct oral anticoagulants (DOACs) (χ2=1.44; p<0.49, Pearson) and significantly more in individuals taking warfarin (as compared to DOACs: χ2=25.08; p<0.000, Pearson; and antiplatelet agents: χ2=34.32; p<0.000, Pearson). Thromboembolic complications were reported in 8.16% of patients. Their number was more in patients taking DOACs than warfarin (χ2=7.03; p<0.03, Pearson). Patients who had to take DOACs according to the algorithm, but in the study took warfarin, demonstrated significantly greater number of thromboembolic complications, with a comparable number of hemorrhagic complications. Patients who could take warfarin according to the algorithm, but in the study took DOACs, had significantly greater number of thromboembolic complications, with a comparable number of hemorrhagic complications.

Conclusion. The results of the study demonstrated the potential for reduction in complications, especially thromboembolic, in the choice of anticoagulant using the algorithm; and reduction in complications of therapy, primarily with warfarin, due to the initial prescription of DOACs. The proposed approach, which consists in using the quantitative assessment of adherence to treatment, and only if necessary supplemented by the assessment of food preferences and/or pharmacogenetic studies, contributes to the treatment optimization.

206-212 517

Aim. To study clinical profile and antihypertensive treatment features in outpatients observed in ambulatory facilities.

Material and methods. 140 arterial hypertension (AH) outpatients were examined, questioning and anthropometry were performed. Blood pressure (BP) was measured on both hands, then twice on the hand with larger value, the medium value was calculated. Tests results were obtained from outpatient cards.

Results. The sampling included 100 (71.4%) females and 40 (28.6%) males. Median of systolic BP at first measurement was 140.0 mm Hg (130.0;150.0), mean value of three BP measurements was 138.0 mm Hg (127.0;150.0) (p<0.001); median diastolic BP at first measurement was 83.0 mm Hg (80.0;90.0), mean BP value was 82.0 mm Hg (78.0;88.0) (p<0.001). Grade 1 AH was identified in 11.4% of patients, Grade 2 – in 35.7%, Grade 3 in 52.9%. No target organ damage was found in 26.4% of AH patients, asymptomatic target organ damage was diagnosed in 26.4%, and 61.4% had associated clinical conditions. Cardiovascular event risk was assessed as moderate in 13.6%, high – in 24.3% and very high – in 62.1% of patients. Every third patient had myocardial hypertrophy signs; Cornell index was detected more often than Sokolov-Layon index (p=0.006). Chronic kidney disease was diagnosed in 65.1% of patients: 44.0% of them had stage C2, 13.8% – stage C3A, 6.5% – stage C3B, and 1.8% – stage C4. 97.9% of AH patients received antihypertensive treatment. Daily medication consumption was reported by 127 people, and 10 patients reported taking medication as needed. Monotherapy was prescribed in 14.3% of patients; combined treatment was performed in 83.6% people. BP target value was achieved in 59 patients (42.1%) at first measurement results and in 71 (50.7%) ones at calculated mean value (p=0.002). Indications for statin use were identified in 86.4% of patients. Statins were administered in 56.2% patients having indications and in 21.1% of subjects without indications (p=0.006). Indications for antiplatelet therapy use were identified in 56.4% of patients. Antiplatelet treatment was administered in 58.2% of patients with indications and in 23.0% of subjects without indications (p<0.001).

Conclusion. Glomerular filtration rate and left ventricular myocardial hypertrophy amplitude criteria calculation allow to diagnose subclinical target organ damage in outpatients at physician visit without additional costs. Compliance with the current antihypertensive therapy guidelines allows to achieve target BP in current practice. Compliance with the BP measuring rules allows to adequately assess the effectiveness of antihypertensive therapy. A significant proportion of AH outpatients have a very high cardiovascular risk, which requires lipid-lowering and antiplatelet therapy.

213-220 427

Aim. To study the long-term dynamics of vascular remodeling in patients with hypertension and high and very high cardiovascular risk when statin is added to antihypertensive therapy with a fixed combination of calcium antagonist and angiotensin converting enzyme (ACE) inhibitor.

Material and methods. Hypertensive patients (n=75) with high and very high cardiovascular risk (age 51.5 [44;58] years) were included in the study. Patients were randomized into two groups. The first group (n=36) received a fixed combination of amlodipine and lisinopril in starting dose of 5/10 mg/day. The second group (n=39) received the same antihypertensive therapy and additionally rosuvastatin (20 mg/day). The follow-up period was 52 weeks. The effect of therapy on the following parameters was evaluated: level of office and average daily blood pressure (BP), central BP in the aorta, augmentation index (AIx), pulse wave velocity (PWV), endothelium-dependent brachial artery vasodilation, carotid intima-media complex thickness, carotid arteries plaque height, and blood lipid profile indicators.

Results. A significant decrease in office and average daily BP was found in both groups: from 171.5 (152;194)/104.5 (97;112) to 140.0 (129;154)/87.0 (83;95) mm Hg and from 142.1 (135;153)/86.7 (83;97) to 124.6 (119;133)/76.5 (73;80) mm Hg, respectively, in the 1st group; from 169.5 (160;190)/103.5 (95;109) to 135.0 (125;141)/83.0 (77;88) mm Hg and from 139.9 (136;152)/86.2 (80;92) to 125.1 (118;134)/74.0 (70;81) mm Hg, respectively, in the 2nd group (p<0.001 for all changes). The frequency of reaching the target office BP level was higher in the 2nd group (p=0.031). Significant decrease in total cholesterol by 33.1% and low-density lipoprotein cholesterol by 50.0% was observed in the group 2. Central BP in the aorta decreased in both groups; the degree of central BP reduction did not differ significantly. AIx decreased from 36.5 (24;41)% to 25.0 (15;36)% (p=0.04) in the 1st group and from 36.0 (30;41)% to 24.0 (20;32)% in the 2nd group (p<0.0001) with a more pronounced decrease in AIx after 24 weeks of therapy (-4.8% and -9.4%, respectively, p=0.036). This trend continued at the end of the observation (-6.4% and -10.8%, respectively, p=0.08). Carotid-femoral and carotid-radial PWV decreased only in the 2nd group from 9.5 (8.2;10.7) to 8.3 (7.6;8.9) m/s (p=0.003) and from 9,6 (8.5;10.6) to 8.4 (7.9;9.3) m/s (p=0.01), respectively. A significant decrease in the thickness of the intima-media from 1.08 (1.0;1.2) to 1.02 (0.9;1.1) cm (p<0.0001) and the height of the plaque from 2.2 (2,2;1.7) to 2.1 (2.1;1.7) mm (p=0.001) was found in the 2nd group.

Conclusion. Addition of rosuvastatin to the fixed combination of amlodipine and lisinopril in treatment of hypertensive patients with high and very high cardiovascular risk was accompanied by a more frequent (compared with amlodipine and lisinopril only) achievement of the target office BP level and more pronounced reduction in the following indicators: augmentation index, carotid-femoral and carotid-radial PWV, intima-media thickness, plaque height, total cholesterol and low density lipoprotein cholesterol blood levels.


221-230 999

Arterial hypertension (AH) is one of the most significant modifiable risk factors that increase cardiovascular morbidity and mortality worldwide, including Russia. The complex of structural and functional changes in the heart that occurs during AH consists not only in the formation of left ventricular (LV) myocardial hypertrophy, but also in the myocardial stiffness increasing due to collagen formation and cardiomyocytes apoptosis. These abnormalities are substrate for diastolic function disturbances, electrical myocardial instability and ischemia. The article provides a clinical case of amlodipine/lisinopril single-pill combination (A/L SPC) use in real clinical practice in a patient with stage II grade 2 newly diagnosed AH and its effect on blood pressure and echocardiographic myocardial fibrosis markers, including speckle tracking parameters The high antihypertensive efficacy of A/L SPC, a favorable effect on blood pressure circadian rhythm, as well as pronounced target-organ protective properties, in particular the ability to reduce LV and left atrial stiffness, were demonstrated. So, we conclude that A/L SPC improve the elastic properties of the left heart.

231-239 684

Aim. To analyze the difficulties of diagnosis and the clinical features of the Danon disease in women.

Results. An observation of Danon disease in a woman aged 18 years with an uncomplicated family history is presented. The early development of atrial fibrillation (at the age of not more than 15 years) in combination with atrioventricular blockade against the background of regular sports was not attracted due attention for 3 years. The examination revealed: a moderate degree of left ventricular hypertrophy (up to 17 mm), its diffuse nature and simultaneous involvement of the right ventricle, signs of heart failure due to severe restrictive disorders with preserved ejection fraction. Cardiac magnetic resonance imaging data (non-specific late gadolinium enhancement) became the basis for the assumption of amyloidosis and the implementation of a myocardial biopsy. An erroneous diagnosis of cardiac amyloidosis according to myocardial biopsy was refuted during a second study, the PAS reaction revealed signs of storage disease. The diagnosis of Danon disease was verified using DNA diagnostics (c.731delG mutation was detected). Due to the presence of unsustained paroxysmal ventricular tachycardia and a high calculated risk of sudden death, cardioverter-defibrillator was implanted. The analysis of literature data on the frequency and the manifestation of Danon disease in women, the place of this disease in the structure of the causes of myocardial hypertrophy is given.

Conclusion. Atrial fibrillation at a young age and left ventricular hypertrophy syndrome can develop due to primary myocardial diseases not well known in the practice of a cardiologist. They require an in-depth diagnostic search; their identification is critical for determining treatment tactics and prognosis.


240-249 528

Aim. To study the influence of social determinants on the frequency of glomerular filtration rate (GFR) categories of various levels, as well as associations with a number of cardiovascular diseases (CVD) and cardiovascular risk factors among the population of four Russian regions included in the ESSE-RF-2.

Material and methods. The study was performed as part of a multicenter epidemiological study “Epidemiology of cardiovascular diseases in the regions of the Russian Federation. The second study (ESSE-RF-2)”. In total, 6681 people 25-64 years old from 4 regions of Russian Federation were included in the analysis. The CKD-EPI formula was used to calculate GFR by blood creatinine level. Groups with normal GFR (≥90 ml/min/1.73 m²), with an initial decrease in GFR (<90 ml/min/1.73 m²), and with a decrease in GFR (<60 ml/min/1.73 m²) were distinguished for statistical analysis. Generalized linear/nonlinear analysis (GLM) was used for multivariate assessment and adjustment of results to socio-demographic characteristics.

Results. The average GFR level in the total sample was 97.8±16.6 ml/min/1.73 m2 ; 29.0% of individuals had an initial decrease in GFR, 1.6% had a reduced GFR. Age was significantly associated with GFR. A statistically significant association with an initial decrease in GFR was found for: hypercholesterolemia (odds ratio [OR] 1.22; 95% clearance interval [95%CI] 1.14-1.30), hypertriglyceridemia (OR 1.09; 95%CI 1.02-1.17), hyperuricemia (OR 1.51; 95%CI 1.39-1.63), no smoking (OR 0.79; 95%CI 0.73-0.85), history of kidney disease (OR 1.13; 95%CI 1.04-1.22). A more pronounced decrease in GFR was associated with the following factors and diseases: arterial hypertension (OR 1.48; 95%CI 1.07-2.05), low level of high-density lipoproteins (OR 1.36; 95%CI 1.04-1.79), hypertriglyceridemia (OR 1.37; 95%CI 1.08-1.76), hyperuricemia (OR 2.49; 95%CI 1.97-3.16), hyperglycemia (OR 1.35; 95%CI 1.01-1.80), a history of myocardial infarction (OR 1.63; 95%CI 1.13-2.36) and kidney disease (OR 1.50; 95%CI 1.16-1.93).

Conclusion. The results of the study indicate a greater number of factors and diseases associated with low GFR compared with the initial decrease, which emphasizes the need for early detection of signs of chronic kidney disease, especially in the elderly, in people with metabolic syndrome, hypertension or diabetes mellitus, as well as a history of kidney disease.

250-257 605

Aim. To identify specific risk factors and features of the course of myocardial infarction (MI) in young patients.

Material and methods. The study design is based on a comparison of observation data for patients of different ages from the Russian RECORD-3 registry (n=2359) and the registry of acute coronary syndrome of the Kemerovo city in 2015 (n=1343). The clinical and anamnestic portrait was determined, the frequency of hospital complications and the “hard” endpoints were evaluated.

Results. Young patients with myocardial infarction (MI) according to RECORD-3 are more often male smokers (p=0.001) with a heredity in cardiovascular pathology (p=0.034), who have an uncomplicated STEMI upon admission to the hospital, and are sent for coronary angiography with stenting (p=0.001), without prescribing statins in the primary and secondary prevention (p=0.050 and p=0.016, respectively). There were no differences with other age groups by endpoints a year later; during the current hospitalization, young patients less often died (p=0.001) or had a relapse of MI (p=0.011). Young patients with MI from Kemerovo were also mostly male smokers (p=0.001), who more often had a history of chronic kidney disease, chronic heart failure, and lipid metabolism disorders (p=0.001), who admitted to the hospital with uncomplicated STEMI, actively undergoing thrombolytic therapy and endovascular diagnosis and treatment (p=0.001). However, it should be noted that these patients were less likely to receive aspirin (p=0.015), dual antiplatelet therapy (p=0.003), angiotensin converting enzyme (ACE) inhibitors (p=0.040) and statins (p=0.001). Moreover, in young patients with MI, deficiency of high density lipoproteins (p=0.005) was more often found in the absence of very high values of low density lipoproteins (p=0.001). Among the complications of inpatient treatment, it should be noted a tendency to bleeding (p=0.001). One year after referent MI a high proportion of repeated non-fatal MI (p=0.005) and deaths (p=0.001) were observed. A comparison of the registries showed that young patients from Kemerovo were more likely to have STEMI (p=0.032), they were more likely to have stenting (p=0.004), they were more often diagnosed with chronic renal and heart failure (p=0.001), and more often ACE inhibitors was prescribed (p=0.017), and MI during hospitalization was more often complicated by bleeding (p=0.003).

Conclusion. From 1.7 to 2.4% of all MI occurs in young patients. The most frequent version of the debut is STEMI. The leading factors of cardiovascular risk in such patients are the male gender, active smoking, a hereditary history of cardiovascular diseases, low cholesterol of high density lipoproteins with insufficient statins prevention. In young patients of the Kemerovo registry, chronic heart failure and chronic kidney disease were more often observed, and ACE inhibitors were prescribed, hospitalization was often accompanied by bleeding. In a young age differences in the frequency and structure of outcomes in one year after referent MI were not found when comparing registries.

258-265 550

Aim. To evaluate the gender characteristics, educational level, cardiovascular diseases (CVD) risk factors and adherence to drug treatment in patients with premature CVD in an outpatient prospective registerу.   

Material and methods. 3690 patients with hypertension, coronary artery disease, chronic heart failure, atrial fibrillation and their combinations were enrolled in the RECVASA registry in Ryazan region of Russia. Groups of patients with early development of CVD (criterion 1 – the age of 18-49 years old, criterion 2 – the age of men 18-54 years old and women – 18-64 years old) were compared with the corresponding older groups. The gender characteristics, educational level, CVD risk factors, and adherence to drug treatment were analyzed.   

Results. According to criterion 1, the age groups of 18-49 years old and ≥50 years old included 347 (9.4%) and 3343 (90.6%) patients, respectively, 144 (41.5%) and 902 (27, 0%), respectively were   men, p<0.0001. According to criterion 2, 1369 (37.1%) patients were assigned to the group with early development of CVD, of which 254 (18.6%) were men under 55 and 1115 (81.4%) were women under 65. The group of older patients included 2321 individuals, of which 792 were men (34.1%) and 1529 were women (65.9%). According to criterion 2, the proportion of men in the group of patients with early development of CVD, was 2.2 times lower, than in the older age group (18.6% vs 41.5%, respectively; p<0.0001). Patients <50 years old were more likely to have higher education, than the group of patients ≥50 years old (42.3 vs 25.9%; p<0.0001), including among both men and women. According to criterion 2, the same statistically significant differences were observed (36.2 vs 21.3%; p<0.0001), including among both men and women. The proportion of smokers was 2 times higher in patients younger than 50 years old, than in patients ≥50 years old (44.0 vs 21.7%; p<0.0001). The largest proportion of smokers was among men and women <50 years old (69.4% and 24.1%, respectively). According to criterion 1, hypercholesterolemia (>5 mmol/L) was diagnosed significantly less frequently in patients with early development of CVD than in the older age group (47.8 vs 54.6%; p=0.047); these differences were obtained due to women (46.9 vs 58.8%; p=0.008), the proportion of individuals with hypercholesterolemia did not significantly differ among men. According to criterion 2, statistically significant differences in the frequency of hypercholesterolemia were not detected among both men and women. There was no differences in the incidence of family history (FH) of premature CVD in the study groups, while the proportion of patients with FH of premature CVD was significantly higher in men <55 years old than in women <65 years old (44.8 vs 37.7%; p<0.0001). According to criterion 1 the proportion of patients with low adherence to treatment was higher in patients with early development of CVD than in the older age group (57.1% vs 46.1%; p=0.0006), the proportion of patients with high adherence was 22.9% and 32.4% (p=0.0013), respectively. According to criterion 2, there were no differences in adherence to treatment.   

Conclusions. According to RECVASA registry, patients with early development of CVD were more likely to be men, in accordance with criterion 1. Patients with early development of CVD, including men and women, according to both criteria, were characterized by a significantly higher proportion of individuals with higher education and a higher proportion of smokers. In patients with early development of CVD using criterion 1, in contrast to criterion 2, hypercholesterolemia was diagnosed significantly less often than in the older age group. It is preferable to use criterion 1 to assess hypercholesterolemia in patients with early development of CVD. The proportion of individuals with FH of premature CVD was significantly higher in men <55 years old than in women <65 years old. Patients with early development of CVD according to criterion 1 were characterized by a lower adherence to drug treatment. Individuals with early development of CVD, especially <50 years old are the target group for comprehensive prevention, not only due to improving the quality of proven effective drug therapy, but also by correcting risk factors and increasing level of adherence to treatment. 


266-272 453

Aim. To study the changes in clinical and demographic characteristics, risk factors, treatment tactics, the dynamics of drug therapy at the prehospital stage and prescribed during discharge from the cardiology department over a 4-year period in patients after acute coronary syndrome (ACS) with ST segment elevation and ACS without ST segment elevation.

Material and methods. Data from the LIS-3 prospective registry (Lyubertsy mortality study) was used. Patients admitted to the cardiology department of the Lyubertsy district hospital No. 2 for the first 9 months of 2014 (n=104) and for the first 9 months of 2018 (n=223) with a diagnosis of “ACS with ST segment elevation and ACS without ST segment elevation” and with a confirmed diagnosis at discharge “acute myocardial infarction” (AMI) or “unstable angina” (NSA) were included into the study. Comparison of clinical and demographic indicators, risk factors, the frequency of use of acetylsalicylic acid, clopidogrel, statins, beta-blockers, ACE inhibitors, angiotensin II receptor antagonists, anticoagulants at the prehospital stage and during discharge from the hospital were performed.

Results. Significant differences in the gender and age composition of patients were not found. The number of working patients increased. Compared to 2014, in 2018 the number of patients with arterial hypertension increased (64.4% and 75.8%, respectively, p=0.047), and with coronary heart disease decreased significantly (39.4% and 22.4%, respectively, p=0.004), however, the incidence of atrial fibrillation, history of AMI, and cerebral stroke did not change over the period under consideration. The frequency of concomitant diseases did not practically change, except for kidney diseases, which have become more common. A significant decrease in the frequency of thrombolysis and a significant (more than 6-fold) increase in angioplasty with stenting were found. Patients before ACS in 2014 received less antiplatelet agents than in 2018, including dual antiplatelet therapy, ACE inhibitors were prescribed more often. The intake of nitrates decreased, and the use of statins increased (6.7% versus 13.9%, respectively, p>0.05). AMI as the outcome of ACS was almost the same in both men and women. A downward trend in myocardial Q-infarction (p>0.05) was found. Taking dual antiplatelet therapy and ACE inhibitors were more often recommended at discharge and taking nitrates and any diuretics was less common. Statins intake did not change.

Conclusion. The “portrait” of a hospitalized ACS patient changed somewhat over 4 years: the frequency of the history of coronary heart disease significantly decreased, and the frequency of hypertension increased. The presence and significance of risk factors such as hypercholesterolemia and adverse heredity cannot be assessed as before. The frequency of use of antiplatelet agents and statins increased in prehospital therapy; however, in general, a smaller proportion of patients requiring statins took them. The proportion of AMI patients among ACS ones did not change over the study period.

273-276 651
The recent discussion about the dangers of using angiotensin-converting-enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA) in patients with COVID-19 is analyzed in the article. There is controversy over the hypothesis that these drugs can be factors contributing to an unfavorable outcome of a viral disease, as well as the absence of any clinical evidence for this hypothesis. The opinion that withdrawal of ACE inhibitors and ARA in patients with COVID-19 may increase the risk of adverse outcomes is presented.


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Chronic noncommunicable diseases represent one of the key medical problems of the XXI century. In this group cardiovascular diseases (CVD) are known to be the leading cause of death which pathogenesis still has the potential to be more profoundly revealed in order to discover its yet unknown but essential factors. The last decades are marked by the active investigation into the gut bacterial role in the initiation and progression of CVD. The result of this investigation has been the appreciation of microbiome as the potentially new cardiovascular risk factor. The development of sequencing techniques, together with bioinformatics analysis allowed the scientists to intensively broaden the understanding of the gut microbiota composition and functions of its metabolites in maintaining the health and the development of atherosclerosis, arterial hypertension and heart failure. The interaction between macro- and microorganisms is mediated through the variety of pathways, among which the key players are thought to be trimethylamine-N-oxide (TMAO), short chain fatty acids (SCFA) and secondary bile acids. TMAO is known due to its role in atherosclerosis development and the increase in major cardiovascular events. In the majority of research SCFA and secondary bile acids have demonstrated protective role in CVD. The great attention is being paid to the role of lipopolysaccharide of gram negative bacteria in the development of systemic low-grade inflammation due to the metabolic endotoxemia which contributes to the progression of CVD. The described interactions draw attention to the opportunity to influence on the certain mechanisms of CVD pathogenesis through the modulation of microbiota composition and function. The review is aimed at highlighting the current data about the mechanisms by which the gut microbiota and its metabolites may increase cardiovascular risk and events rate as well as discussing the existing results and future perspective of bacterial systemic effects modulation.


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This article is a review of epidemiology, pathogenesis and treatment of venous thromboembolism (VTE) in cancer patients. In accordance with actual guidelines, the duration of anticoagulant therapy of cancer-related venous thrombosis should be at least 6 months. The use of vitamin K antagonists (VKA) is associated with an increased risk of VTE recurrence and bleeding, so low molecular weight heparin (LMWH), in particular dalteparin, has been the "gold standard" until recently. Compared to VKA, prolonged use of LMWH can reduce the incidence of VTE recurrence without affecting the risk of bleeding or death. The main disadvantage of LMWH is low compliance, leading to premature discontinuation of treatment or switching to alternative anticoagulants. Direct oral anticoagulants (DOACs) have changed the situation. Compared to VKA, they demonstrated higher efficacy with a similar (or improved for individual DOACs) safety in patients with cancer-related VTE. Recently, the results of studies comparing the use of DOACs with dalteparin in cancer patients have been published: SELECT-D (rivaroxaban), HOKUSAI-VTE Cancer (edoxaban), ADAM VTE (apixaban), CARAVAGGIO (apixaban). Rivaroxaban showed higher efficacy than dalteparin with a similar risk of major bleeding, but an increased risk of clinically relevant non-major (CRNM) bleeding. Edoxaban had the same efficacy as dalteparin but increased risk of major but not CRNM bleeding. Apixaban showed similar efficacy and safety as dalteparin in the CARAVAGGIO study, but did not provide higher safety in the ADAM VTE study. It was noted that gastrointestinal and urogenital bleeding dominated in the structure of hemorrhagic complications of DOACs. The results of published trials are reflected in the current guidelines of the specialized societies. DOACs (particularly, rivaroxaban and edoxaban) are recommended for the VTE treatment in cancer patients.

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Comorbid patients with atrial fibrillation, diabetes mellitus and chronic kidney disease are at high risk of stroke. The direct oral anticoagulants are indicated for them. The choice of a drug should be based on the results of randomized clinical trials, in which the patients profile corresponds to that in the real Russian clinical practice as much as possible. Taking into account the peculiarities of comorbidity in this category of patients, the requirements for their protection should be considered comprehensively. Along with the prevention of thromboembolic complications, it is necessary that the selected direct oral anticoagulant provides a reduction in the risk of cardiovascular complications, which are typical of diabetes mellitus, and slows down the progression of renal filtration function decline. Rivaroxaban may meet these requirements; its use has significant advantage in high adherence to therapy.

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The purpose of this review is to analyze the results of randomized clinical trials, meta-analyses of cohort and observational studies in real clinical practice on the influence of dabigatran etexilate on the risk of myocardial infarction in patients with atrial fibrillation. A pivotal RE-LY study on dabigatran use in patients with atrial fibrillation did not show statistically significant differences in the frequency of myocardial infarction between any of the doses of dabigatran and warfarin, and the risk of coronary events did not depend on the presence of coronary heart disease or myocardial infarction in the patient's history. Subsequently, a number of meta-analyses have reported an increased risk of myocardial infarction when dabigatran was administered to patients with atrial fibrillation. In general, these studies were characterized by conflicting data, which did not allow to draw any definite conclusions regarding the use of dabigatran in relation to the risk of myocardial infarction. Two FDA cohort observational studies were published in 2014 and 2017, and the former was significantly criticized by experts, and the results of the second study did not provide a definitive answer to the question about the importance of the effect of dabigatran on the development of myocardial infarction in patients with atrial fibrillation. Even more "confusing" the problem arose after the publication of meta-analyses of randomized trials, which showed that the risk of myocardial infarction was increased in patients treated with direct oral anticoagulants compared to patients treated with warfarin. This review provides high quality evidence for the efficacy of dabigatran in preventing myocardial infarction and other vascular complications in patients with atrial fibrillation.
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An unhealthy diet takes the lead in the concept of cardiovascular risk factors. It contributes to the development of various so-called “alimentary-dependent” risk factors and conditions: overweight/obesity, hyperglycemia, high blood pressure and hypercholesterolemia. This, in turn, leads to high cardiovascular morbidity and mortality. Many ways to rationalize and improve nutrition have been suggested. But the supremacy in prevention of cardiovascular diseases over the past decades steadily belongs to the Mediterranean diet. The history of origin, its main components, as well as the studies in which its usefulness has been proven, became the subject of this review. In addition, issues of adaptation of the Mediterranean diet to the Russian reality are submitted for discussion.


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This narrative review describes and appraises some relatively new studies investigating the efficacy and safety profile of soluble guanylate cyclase stimulator riociguat in patients suffering from pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). It has been a while since the publication date of pivotal CHEST-1 trial in 2013. New studies available complement existing evidence, expound on specific questions and open new frontiers for CTEPH investigations going forward. In this paper authors attempted to present data from post-hocanalysis of the CHEST-1 study and real-world data on riociguat treatment, confirming the positive effect of the drug on hemodynamic parameters of the pulmonary circulation and the functional status of patients. This effect was shown previously in large randomized trials. The extremely important positive effect of riociguat demonstrated both in the group of inoperable patients with CTEPH and in patients with residual pulmonary hypertension after pulmonary thrombendarterectomy. Of great interest are the presented some authors results of reverse remodelling of the right heart chambers during riociguat therapy in CTEPH patients, including using unique imaging methods (magnetic resonance imaging and positron emission tomography) to evaluate targeted medicinal therapy in terms of right heart remodelling. The safety profile of the drug was analyzed in the long-term post-registration international, multicenter, prospective, observational study EXPERT (NCT02092818), which confirmed the good tolerability and safety of riociguat therapy in PAH and CTEPH patients.

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World experience in off-label medicines use is presented in the article. Data on the history of changes in tactics and approaches to solve the problem of medicines off-label use in the USA and some European countries, as well as in the European Union as a whole, are presented. The reasons, why doctors should use medicines off-label, are discussed. The expert opinion on the conditions ensuring the maximum safety in off-label medicines use is presented. In particular, the validity of obtaining patient informed consent is discussed. The article does not apply to the Russian regulation regarding “off-label” therapy but describes the foreign practice related to off-label medicines use. In addition, the results of some recently completed randomized clinical trials evaluating the effects of direct oral anticoagulants are presented in order to demonstrate the need to clarify the effectiveness and safety of medicines used in certain clinical situations. The results of such studies clarify the indications for the drug use, which are subsequently entered into the summary of product characteristics.


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ISSN 1819-6446 (Print)
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