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Rational Pharmacotherapy in Cardiology

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Vol 13, No 6 (2017)
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https://doi.org/10.20996/1819-6446-2017-13-6

ORIGINAL STUDIES

736-745 167
Abstract

Background. Seasonal variability of cardiovascular morbidity and mortality emphasizes the need for the development of new preventive approaches. One of them could be early diagnostics of the unfavorable blood pressure (BP) phenotypes.

Aim. To evaluate markers of the masked uncontrolled hypertension (MUH) phenotype in winter and summer in ambulatory treated hypertensive patients.

Material and methods. We selected patients from the database (n=477; Ivanovo and Saratov residents) according to the following criteria: regular antihypertensive treatment (AHT), clinical BP<140/90 mm Hg, available clinical and ambulatory BP monitoring (ABPM) data both in winter and summer (MUH and “optimal AHT effect” phenotypes).

Results. The patients with MUH in Ivanovo had a significantly higher body mass index in comparison with patients with optimal AHT effect in winter (29.1±4.4 kg/m2 vs 27.3±3.4 kg/m2; p<0.01), and a higher level of clinical BP. Similar differences were found for clinical heart rate (HR), orthostatic BP and HR. These patients with MUH in summer had significantly higher values of clinical BP and orthostatic systolic BP. In Saratov patients, the MUH phenotype in winter was characterized by a higher prevalence in men (56% vs 38%; p<0.05), a relatively high body height and weight vs these in patients with optimal AHT effect. Similar to the patients from Ivanovo, Saratov patients with MUH in winter had higher clinical and orthostatic BP levels compared to patients with optimal AHT effect. In summer, Saratov patients with MUH had significantly higher body mass index, clinical BP, orthostatic HR and systolic BP. In multivariate analysis, MUH was associated with male sex (p<0.05), obesity Stage 1 (p<0.05) and Stage 2 (p<0.01), and diastolic BP in orthostasis (in particular, diastolic BP≥85 mmHg; p<0.0001). No significant associations were observed for season, city, and other selected factors.

Conclusion. According to our study ABPM could be useful for “unmasking” of the probable MUH both in winter and in summer in patients with target clinical BP on AHT who are obese, have orthostatic diastolic BP ≥85 mmHg and especially in men. Further studies in this area are required, in particular the assessment of the prognostic value of the seasonal dynamics and interrelation of clinical and ambulatory BP.

746-755 156
Abstract

Aim. To study the risk factors associated with the fatal outcome in patients with obliterating diseases of the lower extremities arteries at the stage of outpatient observation.

Material and methods. The study included 467 patients (381 men and 86 women, the median age – 63 years [59;70]) with obliterating atherosclerosis of lower limb arteries >50%. Patients were examined in the framework of the current registry on the basis of the Kemerovo Cardiology Center for the period from 2009 to 2013. The examination included the dynamic observation of an angiosurgeon and a cardiologist, the determination of instrumental and laboratory indicators. During 3 years of follow-up, 42 deaths were registered (8.99% of the total number of patients), including 28 (65%) ones due to cardiovascular diseases. Patients were divided into two groups – with a fatal outcome (9%) and without it (91%).

Results. The lethal outcome was associated with the male gender (83%), disability (69.8%), retirement status (85.5%), higher incidence of previously diagnosed myocardial infarction (38.5%), angina pectoris (66.6%), stroke or transient ischemic attack (19%). Lesions of two (86%) and three arterial basins (36%) and significant coronary bed lesions (74%) were more frequent in patients with lethal outcome, they were characterized by a longer smoking experience (17.9 years) and hypertension (14.5 years). Surviving patients were more likely to undergo reconstructive surgeries on lower limb arteries (26.5%).

Conclusion. Factors associated with death in patients with obliterating diseases of the lower extremities arteries were angina pectoris [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.04-1.43; p=0.041), smoking experience (OR 1.28, 95% CI 1, 8-3,24; p=0,023), the duration of hypercholesterolemia (OR 2.01, 95% CI 0.35-4.12; p=0.012) and intermittent claudication (OR 2.01, 95% CI 0.35-4.12; p=0.041), presence of coronary artery stenosis ≥50% (OR 3.21, 95% CI 2.02-6.14; p=0.031), atherosclerosis of two or more arterial basins ≥50% (OR 3.43, 95% CI 3.46-5.52; p=0.004), the presence of a history of myocardial infarction (OR 2.12, 95% CI 0.75-6.02; p=0.043), and stroke (OR 2.23, 95% CI 2.05-4.21; p=0.021). To improve the effectiveness of secondary prevention in these patients it is advisable to use new organizational approaches at the outpatient stage of their management.

756-763 206
Abstract

Aim. To study the initial disorders in the coagulation system, as factors influencing the development of bleeding during anticoagulant therapy with direct oral anticoagulants (DOAC).

Material and methods. 117 patients receiving DOAC (direct thrombin inhibitors – dabigatran, and Xa factor inhibitors – rivaroxaban and apixaban) were included into the cohort study in parallel groups. In addition to evaluate the efficacy and safety of therapy, an extensive analysis of the blood hemostasis system was performed in patients before the start of anticoagulant therapy.

Results. No thromboembolic events and major bleedings were registered in patients receiving DOAC during 24 month observation. No significant correlations were observed between minor bleeding frequency in both groups (16.33% in dabigatran group and 22.39% in Xa factor inhibitors group) and troponin I and hemoglobin levels, as well as HAS-BLED and ATRIA risk scores. Among patients receiving dabigatran initial decrease in von Willebrand factor plasma level (p=0.02) and increase in fibrinogen blood concentration (p=0.02) were predictors of minor bleedings. These predictors of bleeding events were not found in Xa inhibitor groups.

Conclusions. DOAC in patients with atrial fibrillation showed their efficacy and safety without any differences between classes of direct thrombin inhibitors and Xa factor inhibitors. Among the possible predictors of spontaneous minor hemorrhagic events on the dabigatran therapy, a reduced level of von Willebrand factor and elevated fibrinogen level may be considered when choosing a dose of the drug. Markers of hemorrhagic complications development were not determined for the Xa factor inhibitors. Limitation of this study was the absence of randomization, that is why the results should be interpreted with caution.

764-770 175
Abstract

Aim. To evaluate the features of blood flow at the level of the microcirculatory bed of the skin (MC) in the conditions of comorbid pathology and increased coagulation potential of the blood in patients with atrial fibrillation (AF).

Material and methods. The following groups were formed by random sampling: the main (group 1, n=50) group of patients with paroxysmal or persistent form of AF, after cardioembolic stroke. The comparison group (group 2, n=50) consisted of patients with paroxysmal or persistent AF without a history of stroke. The control group (group 3, n=50) – patients comparable on the basic parameters of patients from groups 1 and 2, but without AF and stroke. The plasma levels of von Willebrand factor (vWF), tissue plasminogen activator inhibitor-1 (PAI-1), antithrombin III (AT III) and plasminogen were determined. All MC parameters were studied with a single-channel laser cutaneous blood flow analyzer for the general practitioner "LAKK-OP" in the area of the finger pad during the period, when a patient had sinus rhythm.

Results. The obtained results indicate the disorders of microcirculation processes in patients with AF after stroke, which are expressed in decrease in tissue perfusion, specific oxygen consumption (I) and relative perfusion of the microcirculation saturation (Sm). Significantly higher levels of vWF, PAI-1 and low levels of AT III were observed in patients with AF and stroke than these in the group of patients with AF. It was found that Sm in patients of the group 1 statistically significantly correlated with vWF (r=-0.61; p=0.0032), plasminogen (r=0.45; p=0.0084), PAI-1 (r=-0.43; p=0.0027) and AT III (r=0.49; p=0.0065).

Conclusion. The revealed disorders of microcirculatory processes are significantly related with the disturbances of the hemostatic function of the endothelium. From the pathophysiological point of view, that is one of the negative risk factors of the development of recurrent thrombus formation.

771-775 191
Abstract

Aim. To study the use of CYP2C19 pharmacogenetic testing (PhGT) for personalization of antiplatelet therapy in patients with acute coronary syndrome (ACS) in routine practice.

Material and methods. The study included 103 patients with ACS without indications for long-term anticoagulant therapy, which underwent CYP2C19 PhGT aimed at antiplatelet therapy personalization.

Results. According to CYP2C19 genotyping the GG, GA, AA allelic variants were detected. CYP2C19*2 PhGT revealed that genotypes GG, GA and AA were carried by 76 (73.8%), 23 (22.3%) and 4 (3.9%) patients, respectively. Initially 86 (83.5%) patients received clopidogrel, 17 (16.5%) – ticagrelor. After therapy correction based on genotype GA and AA, the proportion of ticagrelor receiving patients increased from 25.9% to 55.5% (relative risk=0.172; 95% confidence interval 0.075-0.396; p<0.001). In 40.7% of patients who were poor clopidogrel metabolizers increased clopidogrel doses during maintaining therapy can be associated with the increased risk of bleeding.

Conclusion. PhGT results (detection of carriage of the CYP2C19*2 allele variant) was a significant predictor of antiplatelet therapy correction in ACS patients. Therapy personalization included the replacement of clopidogrel with ticagrelor or an increase in the clopidogrel maintenance dose to 150 mg per day, which did not affect significant clinical outcomes.

776-786 192
Abstract

Working Group of the NIKEA Program. Ekaterinburg: Akulina E.N.; Izhevsk: Shinkareva S. E., Grebnev S.A.; Krasnodar: Kudryashov E.A., Fendrikova A.V.; Krasnoyarsk: Nemik D.B., Pitaev R.R., Altaev V.D., Samokhvalov E.V., Stolbikov Y.Y.; Moscow: Dmitrieva N.A., Zagrebelnyy A.D., Zakharova A.V., Balashov I.S., Leonov A.S., Sladkova T.A., Zelenova T.I., Shestakova G.N., Kolganova E.V., Maksimova M.A.; Novosibirsk: Moskalenko I.V., Shurkevich A.A.; Omsk: Loginova E.N., Gudilin V.A.; Orel: Zhuravleva L.L., Lobanova G.N., Luneva M.M.; Orenburg: Kondratenko V.Y.; Rostov-on-Don: Kalacheva N.M., Kolomatskaia O.E., Dubishcheva N.F., Romadina G.V., Chugunova I.B., Skarzhinskaia N.S.; Ryazan: Bulanov A.V., Trofimova Y.M., Nikolaeva A.S.; St. Petersburg: Savinova E.B., Ievskaia E.V., Vasileva L.B.; Tula: Zubareva L.A., Berberfish L.D., Gorina G.I., Nadezhkina K.N., Iunusova K.N., Nikitina V.F., Dabizha V.G., Renko I.E., Soin I.A.

Aim. To study the adherence to treatment and the factors that affect it in patients with stable coronary heart disease during the treatment with nicorandil. Material and methods. The use of nicorandil in addition to standard antianginal therapy was recommended to patients (n=590) in a prospective, observational, multicenter NIKEA study. Patients completed original questionnaires on adherence, including a Morisky-Green test at the enroll visit. The questionnaires were filled by 423 patients (73% response). The factors that influence adherence were studied.

Results. All patients were divided into 3 groups, depending on the adherence to the use of nicorandil: immediately refused to take the drug (n=150; group 1); started, but stopped taking nicorandil in the first 3 months of observation (n=75; group 2); who took nicorandil for 3 months (n=327; group 3). Potentially adherents (intention to treat) were 582 out of 590 (98.6%) patients, and actually adherents – only 327 of 552 (59.2%) patients. The main reason for non-adherence to the beginning of therapy is polypharmacy; to the continuation of the treatment that had just started – adverse events; for termination of long-term therapy – polypharmacy, adverse events and insufficient effectiveness of treatment. Group 3 had initially more severe angina pectoris: more number of angina attacks (p=0.014) and the need of short-acting nitrates (p<0.0001). Patients of the group 1 compared to the patients of group 3 did not visit the doctors more often or attended them only when necessary, violated the medical prescriptions for taking medications (p<0.05). According to the results of the Morisky-Green test, 150 patients (36.2%) were not are committed to medical recommendations, 264 (63.8%) – are committed. Women were more adherent than men (p=0.47); patients with class I angina were more adherent than patients with class III angina (p=0.027), and patients who regularly attended the treating physician (more often than once a month) were more committed to medical recommendations than patients, not visiting the treating physician (p=0.004).

Сonclusion. The levels of overall adherence according to Morisky-Green test, the potential adherence according to the survey and the actual adherence of patients to treatment vary considerably. The leading cause of non-adherence at the beginning of therapy is polypharmacy, for the continuation of the recently started treatment – the adverse events; for long-term sustained treatment – equally polypharmacy, drug adverse events and the lack of treatment efficacy.

787-793 188
Abstract

Aim. To evaluate the dynamics of the parameters of autonomic balance and electrical instability of the myocardium depending on the effectiveness of the restoration of coronary blood flow in pharmacoinvasive revascularization in patients with acute ST segment elevation myocardial infarction.

Material and methods. The study included 91 patients who underwent effective thrombolytic therapy (TLT) according to the ECG criteria, followed by (3-24 hour later) coronary angiography with percutaneous coronary intervention (PCI). Before and after PCI the telemetric ECG recording was conducted. The dynamics of the temporal and spectral characteristics of heart rate variability (HRV), presence of ventricular late potentials (VLP) and abnormal heart rate turbulence (HRT) were evaluated.

Results. The episodes of ST-segment re-elevation by1 mm or more, lasting at least 1 min, and the dynamics of some HRV indices indicated the development of rethrombosis after TLT. The increase in the mean square deviation of normal intervals to 82.5 (64.5; 94) ms, the average value of the standard deviations of normal intervals calculated over 5-minute intervals throughout the entire recording to 37.5 (31.5; 47.5) ms, the total power of the spectrum and the power of high frequency waves, as well as the decrease in the power of ultra-low frequency waves were found after PCI in the group with a rethrombosis of the infarct-related coronary artery. The analysis of VLP in this group showed an increase in duration of the filtered QRS complex after TLT (to 128.7±34.5 ms), and the root mean square value of the last 40 ms of the QRS complex after PCI (to 49±50.3 μV).

Pathological deviations of the HRT parameters (especially the onset of turbulence) independently on the absolute values were registered more often in patients with rethrombosis, and abnormal values of both HRT parameters were found only in patients with episodes of unstable coronary blood flow.

Conclusion. The results are the indirect evidences of disruption of autonomic regulation of cardiac activity and increased arrhythmic readiness of myocardium in developing rethrombosis of coronary artery. The pronounced reperfusion injury of the myocardium evidently plays an important role in this process and is associated with embolization of the vessels of the microcirculatory bed, release of free radicals and alteration of cardiomyocytes, especially due to prolonged ischemia.

794-799 160
Abstract

Aim. To reveal whether there are differences in subfractional distribution of apo B-containing lipoproteins in men and women with coronary atherosclerosis treated with statins depending on low density lipoprotein (LDL) cholesterol level.

Material and methods. Patients aged 33-85 years with angiography documented coronary atherosclerosis were included into the study (n=133): 97 men (mean age 61±9.0 years) and 36 postmenopausal women (mean age 65±9.3 years). Patients were on statin therapy at least 6 months before admission: atorvastatin (10-40 mg/day), simvastatin (20-40 mg/day), rosuvastatin (10-40 mg/day) and pravastatin (20 mg/day). Subfractional apo B-containing lipoproteins distribution was analyzed by electrophoresis in a 3% polyacrylamide gel.

Results. Men achieving target LDL cholesterol level (<2.5 mmol/l) as compared with those with higher LDL cholesterol level alongside with decreased proatherogenic lipids and apolipoproteins, had less atherogenic LDL subfractional profile: lower portion of LDL 2 (7.3±3.4 и 9.9±3.9%, p<0.01), small dense LDL 3 (1.3±1.2 и 2.2±2.2%, р<0.05), LDL 4 (0.2±0.2 и 0.3±0.5%, p<0.05), and concentration of cholesterol in this subfrtactions. These differences were associated with elevated mean size of LDL particles (270.8±3.0 vs 268.8±3.9 Å, p<0,01). On the other hand, women, despite achieving target LDL cholesterol level, had elevated apo B level and apo B/AI ratio without any differences in subfractional profile of low densities lipoproteins.

Conclusion. In patients with coronary atherosclerosis treated with statins, antiatherogenic shifts in apo B-containing lipoproteins, decrease of cholesterol concentration subfractions coupled by elevation of mean LDL particle size were found only in men who reached target LDL cholesterol level.

800-805 127
Abstract

Aim. To study the incidence of arterial hypertension (HT) and prevalence of risk factors and occupational factors (OF) among people with HT on the base of engineering plant within "The program of formation of healthy lifestyle and prevention of chronic non-communicable diseases among the contingent, attached for the medical assistance for the period 2012-2016".

Material and methods. The study included men (n=586), aged 20-65 years – the workers of the engineering plant directly involved in the works in conditions of industrial occupational exposures. These specified works occupied not less than 50% of the general time, and work experience at the enterprise in examined workers was at least 5 years.

Results. All examined people were divided into 2 groups according to the office blood pressure (BP) levels: without HT – 380 people (64.8%) and with HT – 206 patients (35.2%). HT was observed more often among people without higher education (39.2 vs 28.3%; р<0.07). The prevalence of morphological changes on the fundus of eyes was significantly different in hypertensive patients and people without HT (30.6% vs 21.3%, respectively; p<0.04), that appears to be evidence of early organ disorders. OF were found more often in the group of workers with elevated office BP (31.9% vs 23.2%; p<0.04). Metabolic syndrome were detected in 44.8% of hypertensive patients vs 22.4% in people without HT (p<0.001). The people with HT but without other components of metabolic syndrome were taken for particular analysis. In this group the higher education was also much less often (24.0% vs 57.6%; p<0.001), and OF (excluding work at the computer) were revealed more often (87.3% vs 80.2%; p <0.06).

Conclusion. The development of HT in workers of engineering plant is influenced, firstly, by "traditional" risk factors – age and components of metabolic syndrome, and higher education is a kind of HT "anti-risk factor". OF were significantly more common in the group of workers with elevated office BP. Periodic checkups should be the routine method to identify chronic non-communicable diseases among people of working age.

NOTES FROM PRACTICE

806-812 163
Abstract

The article presents a rare clinical case of thrombosis of large and small branches of the pulmonary artery, the probable cause of which was the degeneration of the muscle fibers of the wall of the pulmonary artery trunk by type of the cystic medionecrosis, possibly having a viral etiology. The disease was associated with the tumor of the pancreas body, smoldering purulent pancreatitis complicated by the syndrome of disseminated intravascular coagulation.

813-818 233
Abstract

The clinical case of acute myocardial infarction during a therapy with capecitabine is considered. Cardiovascular diseases and cardiovascular risk factors were not detected before the anticancer treatment. In a week after start of the fluoropyrimidine therapy, a routine electrocardiography revealed the acute phase of myocardial infarction of the lower localization. The diagnosis was confirmed by biochemical blood tests. The administration of capecitabine was discontinued. An urgent coronary angiography did not find obstruction of the coronary arteries. Thus, according to the results of a standard therapeutic examination of the patient, it was impossible to predict the development of capecitabine-induced cardiovascular toxicity before the start of anticancer therapy, as well as diagnose it clinically.

PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH

819-826 190
Abstract

Aim. To study the association of heart rate (HR) with the health parameters obtained in the ESSE-RF study.

Material and methods. The data of the multicenter epidemiological study of ESSE-RF were used in the work. 8,343 men and 13,531 women aged 25-64 years were examined. The response to the survey was about 80%. The analysis is performed depending on the elevated heart rate. Education, place of residence, region, lipid profile, levels of C-reactive protein (CRP) and glucose, history of diabetes, anxiety and depression, elevated blood pressure were analyzed as factors possibly associated with increased heart rate. Epidemiological diagnosis of ischemic heart disease (IHD) was established using the Rose questionnaire, an electrocardiogram analysis, followed by the Minnesota code coding.

Results. Almost every fifth inhabitant had a pulse rate of more than 80 beats/min. No significant difference was found between the sexes. The increase in heart rate in men, starting in the age group 25-34 years to 45-54, and in women only up to 35-44 years with subsequent reduction in men and women was found. The prevalence of increased heart rate varies from region to region. The highest heart rate in men is recorded in Orenburg (33.1%), Ossetia (Alania) and Volgograd (29.7% and 27.6%, respectively), in women – in Vladivostok (37.4%), and the lowest heart rate in both gender groups

– in Samara (9.4% for men and 8.1% for women). Increase in heart rate in men with secondary education [odds ratio (OR) 1.24; 95% confidence interval (CI) 1.10-1.40], smokers and quitters (OR 1.90, 95% CI 1.63-2.27), who did not drink alcohol during the last year (OR 1.18, 95% CI 1.021.37), living in rural areas (OR 1.22, 95% CI 1.04-1.42), who are obese (OR 1.27, 95% CI, 1.101.45), having elevated blood pressure (OR 2.24, 95% CI 1.88-2.67), elevated levels of triglycerides, glucose and CRP was found after correction for age, region and all indicators included in the analysis (multidimensional model). The heart rate >80 beats/min was found significantly less often in people with history of myocardial infarction. A different model was found in women, it included, like in men, living in the village, elevated levels of blood pressure, triglycerides, glucose and CRP, but not education, smoking and alcohol consumption, obesity. Anxiety, low level of high-density lipoproteins and history of diabetes mellitus were also in the model in women.

Сonclusion. Significant associations between increased heart rate and metabolic risk factors, inflammation and residence in the village are found.

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY

827-834 132
Abstract

Aim. To assess the changes in prehospital treatment of patients with acute coronary syndrome during the last years on the basis of the LIS-3 registry data.

Material and methods. Data of acute coronary syndrome hospital registry LIS-3 (2013-2015, n=397) and acute myocardial infarction hospital registry LIS-1 (2005-2007, n=1133) were used. To assess quality of prehospital treatment the fact of taking specific pharmacological groups of medications for primary and secondary cardiovascular diseases prevention was taken into consideration.

Results. Patients in the LIS-3 registry, in comparison with patients in the LIS-1 registry, more often took antiplatelet drugs (23.2% vs 15.7%, respectively; p<0.01) and statins (4.9% vs 2%, respectively; p<0.01). However, in general, the frequency of prescribing these groups of medications remained low. The use of medications of other pharmacological groups was comparable in patients of LIS-1 and LIS-3 registries (p>0.05). The quality of prehospital treatment did not differ significantly in survived and deceased patients of LIS-3 registry (p>0.05).

Conclusion. Only slight improvement in the quality of prehospital therapy in patients with acute coronary syndrome was revealed, mainly due to more frequent use of antiplatelet drugs and statins. It may be explained by poor detection of early forms of ischemic heart disease and underestimation of the importance of risk factors correction, both on the part of patients and on the part of physicians.

INNOVATIVE CARDIOLOGY

835-840 146
Abstract

While there are an increasing number of antithrombotic agents with demonstrated clinical efficacy, thrombosis remains the leading cause of mortality in developed countries. Therefore, there is a need further development of therapies targeting alternative components of the blood clotting mechanism, based on new knowledge about the mechanisms of thrombus formation. Recently, among several unexpected findings of new methods and approaches to the study of these mechanisms it was discovered that protein disulfide isomerase (PDI) serves an essential role in the processes of thrombus formation. PDI is secreted by platelets and endothelial cells following activation and localizes to the membrane surface. Given the role of PDI in regulating both platelet aggregation and fibrin generation in vivo, the possibility of using PDI as an antithrombotic target is discussed. While most antithrombotic target either platelet or coagulation activation, PDI inhibitors have the potential to prevent thrombosis in conditions with pathologic activation of both pathways as implicated in complex thrombotic disorders such as myocardial infarction and cancer associated thrombosis. This review considers what is known about the role of PDI in thrombus formation, main targets and mechanisms of action, as well as PDI inhibitors, as candidates for a new class of antithrombotic agents with both antiplatelet and anticoagulant properties to prevent thrombosis in humans.

POINT OF VIEW

841-850 215
Abstract

Advantages of amlodipine, lisinopril and their fixed-dose combination are presented regarding to antihypertensive effect and target-organs protection in patients with arterial hypertension in the presence of obesity. Abnormalities in myocardial strain, increased stiffness of the left heart chambers, left ventricular hypertrophy are considered as "new" risk factors in hypertensive patients along with disturbances in some parameters of blood pressure and its daily profile. Current data about various pathophysiological mechanisms of the favorable impact of calcium channel blockers, as well as angiotensin-converting enzyme inhibitors, are described, in particular, lisinopril-mediated beneficial effects on myocardial stiffness and regression of myocardial hypertrophy.

851-855 169
Abstract

The main positions of the American guidelines on management of patients with hypertension and concomitant ischemic heart disease (2015) are discussed in the article. Questions about the target blood pressure levels and the choice of the main classes of antihypertensive drugs, depending on the history of myocardial infarction, diabetes mellitus, and chronic kidney disease are presented. The principles of management of hypertensive patients with stable angina and acute coronary syndrome are discussed separately. The place of amlodipine in the therapy of patients with hypertension and ischemic heart disease is also being considered. Analysis of the large number of patients presented in the VALUE, CAMELOT and PREVENT studies allows one to more reliably talk about the pleiotropic effects of amlodipine and to determine its place in the antihypertensive therapy of patients with subclinical and symptomatic atherosclerosis. Possible potentiating effect of angiotensin converting enzyme inhibitors and amlodipine is also discussed in the article. This allows us to consider amlodipine as one of the key components of antihypertensive therapy in patients with ischemic heart disease, which contributes not only to accelerated normalization of blood pressure but also to a decrease in cardiovascular risk.

856-862 152
Abstract

Atrial fibrillation (AF), being both a cause and a consequence of chronic heart failure (CHF), occurs with it significantly more often than in the general population. Prevention and treatment of AF in patients with CHF has its own specifics and presents certain difficulties for practical physicians of various specialties. The article presents a modern view of primary and secondary prevention of AF in patients with CHF and a critical analysis of international recommendations on the use of various antiarrhythmics and not antiarrhythmic drugs, anticoagulants and non-drug treatments in these patients. Based on the analysis of a number of studies, it has been shown that in patients with AF and CHF, the sinus rhythm control strategy has no advantages over the rate control strategy. The review also examines the possibilities of drug therapy in rate control strategy in CHF, depending on the size of the left ventricular ejection fraction, as well as indications for interventional prophylaxis of the AF paroxysms. At the same time, it discusses some questions about the choice of tactics for management of patients with AF and CHF, electrical and pharmacological cardioversion and prevention therapy, features of AF treatment in certain diseases and syndromes. The article also presents a critical evaluation of interventions in the treatment of AF, such as catheter ablation of AF, catheter ablation of additional routes and destruction of the AV node in combination with the pacemaker implantation.

863-870 129
Abstract

A clinical role of biomarkers (especially, natriuretic peptides) is discussed in the article. The most important evidences of clinical effectiveness of using biomarkers in patients with suspected heart failure and in patients with confirmed diagnose of heart failure are reviewed. The need to use natriuretic peptides in patients with takotsubo syndrome is discussed. Limited diagnostic value of using natriuretic peptides in renal dysfunction, as well as in other diseases in which the concentration of natriuretic peptides may increase in the absence of heart failure, is also discussed.

871-879 275
Abstract

The prevalence of smoking in the Russian Federation is 27.7%. Losses of potential years of life in working age associated with premature death due to smoking in Russia on average are 9 years for men, for women – 5.6 years. Tobacco use is a risk factor for 6 of 8 main causes of death in the world: ischemic heart disease (IHD); cerebral circulation disorders; lower respiratory tract infection; chronic obstructive pulmonary disease; tuberculosis; trachea, bronchus, and lung cancer. The risk of developing IHD in smoking patients is increased by 2-4 times in men and women and in any age group. Myocardial infarction occurs in smoking patients at a younger age, and they have a similar risk of coronary events with patients of older age groups. The increased risk of recurrent coronary events persists with the continuation of smoking in the patient after myocardial infarction. Smoking is associated with a double risk of ischemic stroke and a 2-4-fold increase in the risk of subarachnoid hemorrhage. The risk of peripheral arteries diseases in smokers is increased 3-6 times than this in non-smokers. The mechanisms of development of acute cardiovascular events during smoking include the activation of inflammation, platelet aggregation/thrombogenesis, the sympathetic nervous system, and the development of endothelial dysfunction due to exposure to tobacco smoke components.

CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY

880-884 197
Abstract

Data on the mechanisms of cardiomyocyte apoptosis in myocardial infarction are presented. It has been experimentally established that the ratio of the number of cardiomyocytes with signs of apoptosis and necrosis is 30:1 already 2 hours after acute artery occlusion. This fact points out the leading role of apoptosis in cardiomyocyte death in acute period of myocardial infarction. Cardiomyocyte apoptosis makes a significant contribution in myocardial remodeling and left ventricular dysfunction after myocardial infarction. The essential role of active forms of oxygen in the development of cell apoptosis after reperfusion was proved in experimental data. Carvedilol is a third-generation beta-blocker with additional pleiotropic and antioxidant effects. The multifactorial positive influence of carvedilol on apoptosis prevention gives the opportunity to adopt experimental results into real-life clinical practice. It was established in vivo that administration of carvedilol just after start of coronary reperfusion decreases by 77% the number of cells suffered from apoptosis. Carvedilol has antioxidant effects and prevents cell apoptosis due to reduction in calcium concentration in mitochondrial matrix. The experimental results and the data of large randomized clinical trials give an opportunity of using carvedilol in treatment of myocardial infarction to decrease necrotic zone and prevent cardiomyocyte apoptosis.

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ISSN 1819-6446 (Print)
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