Rational Pharmacotherapy in Cardiology

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Vol 13, No 1 (2017)
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4-17 661

Aim. To study particularities of course and outcomes of acute cerebrovascular accident (ACVA), quality of examination and medical treatment within a framework of an outpatient register.

Material and methods. Two outpatient registries were organized on the base of one of Ryazan outpatient clinics within a framework of the pilot phase of the REGION study: the register of patients who had experienced ACVA of any remoteness (ACVA-AR register, n=200) and the register of patients who had visited the outpatient clinic for the first time after cerebral stroke (ACVA-FV register, n=115). Particularities of ACVA development, concomitant cardiovascular diseases (CVD) and noncardiac diseases were analyzed. We estimated accordance of methods of examination and prescribed medical treatment with clinical guidelines. Long-term outcomes were also evaluated in the course of prospective follow-up.

Results. Patients of both  registers had  concomitant CVD (on an average 3 diagnosis) and  noncardiac comorbidity (on an average 1 diagnosis). Majority of patients at the outpatient phase  received inadequate treatment for cardiovascular risk decrease, especially before  reference ACVA. The ACVA-FV register patients as compared to the ACVA-AR ones (who had experienced ACVA on an average 4.8 years earlier) were more often (p<0.05) examined by instrumental and laboratory methods of diagnostics during the post-stroke follow-up in outpatient settings. ACVA-FV register patients as compared to the ACVA-AR ones were also more often (p˂0.05) prescribed prognosis-modifying therapy (statins – 46.9% vs 11%, acetylsalicylic acid – 54.8% vs 28%, ACE inhibitors – 46.1% vs 29%, and anticoagulants in atrial fibrillation – 17.6% vs 2.3%, respectively). Mortality rates in the ACVA-AR and ACVA-FV registers for 2 years were 15.5% and 32.2%, respectively (p=0.005), incidence rates of myocardial infarction – 2.5% and 0%, respectively (p=0.09), recurrent ACVA – 14.5% and 11.3%, respectively, (p=0.42).

Conclusion. Examination and medical treatment of the patients in the outpatient clinic were suboptimal especially before  ACVA development. However examination and treatment quality had improved significantly (although insufficiently) during 5-year time span between ACVA development in the ACVA-AR and ACVA-FV registers. High mortality rate (22.7%) in the first 3 months of outpatient follow-up after ACVA is an unsolved challenge.

18-24 552
. Aim. To study the effectiveness of antiarrhythmic drugs: propafenone, sotalol and verapamil for the prevention of recurrence of atrial fibrillation (AF) and other atrial tachyarrhythmias in the early postoperative period after pulmonary vein ostia catheter isolation in patients with paroxysmal AF.

Material and methods. Patients (n=243) were included into a prospective, comparative, open-label, randomized study with a control. They were divided into 4 groups: Patients of Group 1 (n=61) received verapamil retard 240 mg/day., Group 2 (n=62) – propafenone 450 mg/day, group 3 (n=60) – sotalol 160 mg/day. Patients of control Group 4 (n=60) did not receive antiarrhythmic drugs. Patient's diary, ECG, 24-hour Holter ECG monitoring, and percutaneous heart monitor were used to detect arrhythmias in the early postoperative period.

Results. During the first 3 months of postoperative period we registered 8.62±9.37 pharmacological cardioversions in Group 2, 13.24±10.77 in Group 1 (p=0.013), and 11.93±12.02 in Group 3 (p=0.123). Besides we performed 0.40±1.03 electrical cardioversions in Group 2, 1.016±1.74 in Group 1 (p=0.024), and 1.033±1.52 in Group 3 (p=0.0096). A number of hospitalizations was 0.447±0.57 in Group 2, 0.684±0.73 in Group 1 (p=0.0012), and 0.592±0.67 in Group 3 (p=0.074).

Conclusion. Better clinical effectiveness for prevention of atrial tachyarrhythmias recurrence in the early postoperative period was found in the propafenone group.

25-30 768

Aim. To study changes in course of arrhythmias, depending on the efficacy of coronary blood flow restoration due to pharmacoinvasive revascularization in patients with ST segment elevation myocardial infarction (STEMI).

Material and methods. STEMI-patients (n=117) with an effective (according to ECG criteria) thrombolytic therapy (TLT) and the subsequent (after 3-24 hours) percutaneous coronary  intervention (PCI), were included into the study. Telemetry ECG was performed before  and after PCI with analysis of the arrhythmias and cardiac conduction disorders.

Results. Patients (n=84; 71.8%) with an effective TLT, confirmed by the coronary angiography (CAG), and with subsequent effective PCI were included into the group "without rethrombosis" (RT(–)). Patients (n=33; 28.2%) with CAG proven rethrombosis of the infarct-related coronary artery and subsequent effective PCI were included into the group "with rethrombosis" (RT(+)). Regardless of the stability of coronary blood flow restoration after the TLT, PCI was associated with an increased incidence of ventricular tachycardia (VT) (p<0.01), sinus tachycardia (p=0.01), paroxysmal supraventricular tachycardia (SVT) (p<0.05) and paired ventricular extrasystoles (p<0.01). Compared to the RT(–) group, in the RT(+) group after PCI VT were recorded more frequently (44% vs 63.6%, respectively; p<0.05) as well as AV-block 3 degree (3.6% vs 12.1%, respectively; p<0.05). Episodes of sinus tachycardia were detected significantly more frequently before PCI in RT(–) group compared with RT(+) group (67.9% vs 45.4% respectively; p<0.01). The number of patients with episodes of sinus bradycardia increased (from 19% to 32.1%; p=0.02) after PCI in RT(–) group.

Conclusion. The incidence of VT and SVT paroxysms, episodes of sinus tachycardia, atrioventricular conduction disturbances and ventricular extrasystoles increased in all patients after the effective PCI due to reperfusion. However, VT episodes and paroxysmal atrioventricular block grade 3 were more common in patients with previous re-thrombosis of the infarct-related coronary artery. Considering a high risk of arrhythmic events, continuous ECG mon itoring with automated alarm systems  about life-threatening arrhythmias should be applied in STEMI patients regardless of tactics of coronary  blood flow restoration and the reperfusion effectiveness.

31-35 490

Aim. To study the socio-behavioral, instrumental and laboratory parameters and quality of life of patients with arterial hypertension (HT) and comorbid conditions.

Material and methods. The study included 64 patients of both  sexes, aged  30-69 years. All patients were divided into 3 groups:  patients with HT (I group, n=20; 52.7±9.9 years old); patients with HT and diabetes mellitus (DM) type 2 (II group, n=23; 58±5.3 years old); and HT patients with chronic obstructive pulmonary disease (COPD; III group, n=21; 57±7.2 years old). Clinical symptoms, anamnesis, resting heart  rate were evaluated as well as blood pressure measurement, echocardiography and biochemical analysis of the blood were performed. Quality of life was also assessed with the international questionnaire EQ-5D.

Results. Combination of HT and COPD was more common in women than in men (66.7% vs 33.3%), and a body mass index >30  kg/m2 was typical for the majority of patients with the HT and DM (34.1±9.1 kg/m2), HT and COPD (33.6±6.7 kg/m2). The assessment with the questionnaire EQ-5D showed that a more pronounced decrease in the quality of life was in patients with HT and DM. Quality of life in groups  II and III was worse than  in group  I (1.7±1.3 and 1.4±1.5 vs 0.9±0.86 scores,  respectively). The combinations of HT with DM and HT with COPD were accompanied by increased plasma creatinine levels (88.6±14 and 88.5±11.7 mcmol/L, respectively) and more severe dyslipidemia.

Conclusion. In patients with HT concomitant DM and COPD contribute to the quality of life reduction, increase in plasma creatinine levels, and more severe dyslipidemia.

36-44 601

Aim. To study the ranges of low density lipoprotein (LDL) cholesterol depending on the age and gender of patients with familial hypercholesterolemia (FHC) by an example of a sample of patients living in the Republic of Karelia.

Material and methods. Parameters of lipid spectrum of 219 patients (aged 52.5±1.7 years; males 38.3%) with heterozygous FHC were studied before the start of statin therapy. Definite FHC was diagnosed in 102 patients. Lipid profile was estimated by enzymatic calorimetric method. The diagnosis of FHC was established according to the criteria of The Dutch Lipid Clinic Network.  Genetic analysis was performed in 102 patients (46.6%); pathogenic mutation in the LDL receptor was identified in 21 patients. The control group consisted of 539 people with the excluded diagnosis of FHC (aged 46.8±0.8 years; males 53.8%).

Results. We determined the level of LDL cholesterol (LDLC) associated with increased frequency of mutations of the LDL receptor in patients with definite FHC; mutation frequency was 3 times higher when LDLC level was more than 6.5 mmol/L. We revealed the following characteristic intervals of the LDLC levels in patients with a definite FHC: up to 20 years old – 4.8-6.2 mmol/l; in patients of 20-29 years old – 5.9-8.2 mmol/l; in the age range of 30-39 years the upper value of the LDLC levels reached 9.6 mmol/l; in individuals of 40-49 years old a stabilization, "plateau", was observed – LDLC level did not differ significantly compared to the previous decade, and was 5.4-9.0 mmol/l. In the age range  of 50-59 years the upper LDLC level was up to 11.4 mmol/l. Similar indicators were identified in patients aged 60-69 years. Patients older than 70 years with a definite FHC an upper level of LDLC was higher and reached 12.5 mmol/l. Tendency to increase in the characteristic values of LDLC with age was observed both in men and in women. Specific age-related trends  for men (an increase from a plateau by the age of 50 years, with some decrease after 60 years) and women (smooth increase of LDLC levels with age) were demonstrated.

Conclusion. Characteristic values of LDLC levels for the Russian population of patients with FHС were shown; relationship between LDLC levels and detection of mutations of the LDL receptor was analyzed.

45-50 700

Aim. To compare cost-effectiveness of the use of direct factor Xa inhibitors rivaroxaban and apixaban in patients with non-valvular atrial fibrillation (AF) and to assess the impact of the both therapies on the healthcare budget of Russian Federation.

Material and methods. Pharmacoeconomic analysis with "decision tree" modeling is performed. The costs of regimens using rivaroxaban and apixaban were calculated. Assessment of the likelihood of cerebrovascular complications during anticoagulant therapy was performed, and the average additional costs in development of adverse  clinical effects were calculated. The average costs of treatment regimens used in view of the probability of occurrence of all the clinical effects,  were calculated as a result of the modeling.

Results. The results of the pharmacoeconomic analysis shown, that the strategy of the use of rivaroxaban for stroke prevention in patients with non-valvular AF is less costly 49558.43 rubles for one patient per year. The strategy of apixaban application costs higher by 0.15% (50027.57 rubles). Cost reduction for the year of rivaroxaban therapy in a cohort  of 1000 patients was 469140 rubles due to decrease in the incidence of cerebrovascular complications in comparison with apixaban therapy.

Conclusion. When choosing pharmacotherapy strategy to prevent the stroke in patients with non-valvular AF rivaroxaban use is more effective, than the use of apixaban, from the clinical and pharmacoeconomic points of view.


51-54 452

Aim. To assess effectiveness and safety of the hospital use of recombinant non-immunogenic staphylokinase in patients with acute  ST-elevated myocardial infarction (STEMI).

Material and methods. Recombinant non-immunogenic staphylokinase was administered during in-hospital stage of treatment of 93 patients with acute STEMI, followed by clinical and electrocardiographic assessment and angiographic verification of the degree of blood flow in the infarct-related coronary  artery. Hemorrhagic complications, allergic reactions, and hospital mortality were also considered.

Results. When monitoring electrocardiogram after 90 minutes from the first bolus of recombinant non-immunogenic staphylokinase, the decrease of ST segment by 50% to the isoline was found in 93.5% of patients. Intracranial and extra brain major and small bleedings were not observed, as well as allergic reactions. In the group of patients who underwent coronary  angiography (n=15), antegrade blood flow TIMI 3 was visualized in 100% of cases. Hospital mortality was 6%.

Conclusion. Modern thrombolytic drug of recombinant non-immunogenic staphylokinase demonstrated high effectiveness in recovery of blood flow in the infarct-related coronary  artery,  hemorrhagic safety,  and easy to use in the bolus administration.


55-62 531

Aim. To study a treatment of patients with acute  myocardial infarction (AMI) before  and during hospitalization in a Khabarovsk  hospital, which has an opportunity of primary percutaneous coronary  intervention (PCI), as well as hospital outcomes according to the AMI Register.

Material and methods. 321 patients consecutively hospitalized in the Khabarovsk  Regional Vascular Center were included into AMI Register: 177 patients with ST-segment elevation AMI (STEMI; 55.1%); 135 patients non-ST-segment elevation AMI (non-STEMI; 42.1%); 9 patients with early recurrence of AMI and early post-infarction stenocardia (2.8%).

Results. Before reference AMI a frequency of administration of statins was 13.7%, angiotensin-renin blockers – 29.3%, acetylsalicylic acid – 28.7%, beta-blocker – 25%. Among patients with atrial fibrillation only 7 ones (17%) were treated with oral anticoagulants.        141 patients (79.6%) with STEMI underwent PCI procedure: primary PCI – 82.3% and delayed PCI – 17.7%. PCI with coronary  stenting was performed  in 86.5% of patients with STEMI. Frequency  of PCI in non-STEMI patients was 42%: primary PCI – 43.9%, delayed PCI – 56.1%, PCI with coronary stenting – 43.9%. Gender and age of the patients did not influence the choice of tactics of revascularization in STEMI and non-STEMI (PCI(+), PCI(-), PCI with coronary  stenting) (p<0.05).

Medication in hospital: double antithrombotic therapy (DATT) was prescribed in 86.9% of patients; direct anticoagulants – in 91.2%, statins – in 97.2%, beta-blockers – in 88.5%; renin-angiotensin-aldosterone system inhibitors – in 90.6%. A total lethality in STEMI was 15.2%, and in non-STEMI – 1.5%. Lethality in PCI-negative patients with STEMI was higher than  this in patients with non-STEMI (p<0.001). In STEMI patients lethality was 3.3  times lower in PCI-positive patients in comparison with PCI-negative patients.

Conclusion. AMI Register demonstrated that before reference AMI very few patients were covered with modern medicines influencing prognosis. AMI hospital treatment in Khabarovsk Regional Vascular Center was characterized by a high rate of primary PCI, DATT, enoxaparin, and high-dose statin therapy.


63-68 737

Aim. To compare a «portrait» of a patient and hospital lethality between register LIS-1 of myocardial infarction (MI) and register LIS-3 of acute coronary syndrome (ACS).

Material and methods. We compared two registers held in Lubertsy town: MI register LIS-1 (2005-2007) and ACS register LIS-3 (01.11.2013-31.07.2015). LIS-1 is a retrospective study; information about patients survived and died in hospital was taken from medical histories. LIS-3 is a prospective study; data on survived patients was collected from questionnaires and medical histories, information about died ones – from medical histories.

Results. «Portrait» of a patient of LIS-1 and LIS-3 registers was comparable in gender, age, history of MI, arterial hypertension, atrial fibrillation, and stroke. LIS-3 patients had diabetes mellitus more often, and on the contrary, history of ischemic heart disease (IHD) and angina pectoris – more rarely than  LIS-1 patients. ACS was the first manifestation of IHD in 64% of LIS-3 register patients and 31.4% of LIS-1 register patients. Hospital lethality was 15.2% in LIS-1 register and 19.4% in LIS-3 register (p>0.05). Hospital lethality increased in elderly patients in both  registers. Atrial fibrillation increased hospital lethality risk in LIS-3 register and long-term mortality risk in LIS-1 register. History of arterial hypertension and angina pectoris re duced hospital lethality risk in LIS-3 register. In LIS-1 register neither of these factors was significant, but left ventricular hypertrophy reduced hospital mortality risk.

Conclusion. LIS-1 and LIS-3 patients were comparable in many factors, bud differed in history of IHD (31.4% in LIS-1 register, 64% in LIS-1 register) and angina pectoris. Factors associated with hospital mortality differed in the two registries.


69-79 1085

The need to maintain a high quality of life against a backdrop of its inevitably increasing duration is one of the main problems of modern health care. The concept of "right drug to the right patient at the right time", which at first was bearing the name "personalized", is currently unanimously approved by international scientific community as "precision medicine". Precision medicine takes all the individual characteristics into account: genes diversity, environment, lifestyles, and even bacterial microflora and also involves the use of the latest technological developments, which serves to ensure that each patient gets assistance fitting his state best. In the United States, Canada and France national precision medicine programs have already been submitted and implemented. The aim of this review is to describe the dynamic integration of precision medicine methods into routine medical practice and life of modern society. The new paradigm prospects description are complemented by figures, proving the already achieved success in the application of precise methods for example, the targeted therapy of cancer. All in all, the presence of real-life examples, proving the regularity of transition to a new paradigm, and a wide range  of technical and diagnostic capabilities available and constantly evolving make the all-round transition to precision medicine almost inevitable.

80-87 565

Stroke is one of the most frequent causes  of death and permanent disability among adults. The majority of ischemic strokes  are due to atherosclerotic plaque in the internal carotid artery. Carotid endarterectomy is more effective than medical management in the prevention of stroke in patients with carotid artery stenosis. Carotid artery stenting, a less invasive revascularization strategy than  endarterectomy, is also wide-spread but it is associated with more periprocedural complications. Knowledge of risk factors of these  complications may impact treatment decisions for the individual patient, but these factors have not been extensively studied.


88-94 964

Aim. To study changes in the glycoproteins content in the glycocalyx of endothelial cells under the influence of magnesium orotate.

Material and methods. Endotheliocytes of cell culture EA.hy 926 were examined before  and after addition of the magnesium orotate to the culture medium. Intimal endothelium of internal carotid arteries, fragments of which were obtained by sequential execution of bilateral resection of the arteries before  and after course of treatment with magnesium orotate was also investigated. Anthony’ method (1931), designed for the study of glycoproteins in the bacteria capsule and adapted by L.V. Didenko (2013) for eukaryotes was used to detect glycoproteins. The scanning electron microscopy with simultaneous x-ray microanalysis was applied.

Results. Total number of Cu2+-signals per one scanning field in the mapping of samples for Cu2+ as the indirect index of proteoglycan content in EA.hy 926 endothelial cell culture before incubation with magnesium orotate was 6928±124, and after incubation with magnesium orotate – 7592±131. Number of Cu2+-signals on the surface of the internal carotid artery intima before treatment with magnesium orotate was 5015±407, and after treatment – 6100±152 per one scanning field.

Conclusion. A significant increase in the content of glycoproteins on the surface of EA.hy926 endothelial cell culture (+10%) and internal carotid artery intima (+22%) under the influence of magnesium orotate was found.


95-99 902

The review actualizes the need to validate data  obtained in randomized clinical trials (RCT) by the results of routine clinical practice (RCP). Definitely, both methods have some disadvantages. Only patients with minimal comorbidity and a number of other restrictions are included into the RCT in accordance with strict procedures and treatment protocol. On the contrary, the analysis of the RCP shows that data  bases  of insurance companies and medical records are associated with less exact information about the patients, heterogeneity of comparison groups might be significant, and end points evaluation can be different. At the same time, if the RCT data are confirmed by the key results of the RCP analysis, it is a strong  evidence of the credibility of information, obtained by the both methods. The analysis of various RCP data bases published over the past 2 years shows that, among all new oral anticoagulants, apixaban is associated with the best adherence to treatment and lowest bleeding incidence in patients with non-valvular atrial fibrillation. These results confirm good safety profile of apixaban which was previously demonstrated in ARISTOTLE trial. On the contrary, rivaroxaban was associated with the most frequent bleeding in long-term use in patients with atrial fibrillation.

100-106 2881

Disorder of formation of vitamin B12, which has a wide range  of biological properties and is involved in the regulation of many important physiological functions, is the basis of a number of serious diseases. Usually internists consider that vitamin В12 deficiency is associated with disturbances of hematopoiesis or central nervous system. However cobalamin deficiency also affects the state of the cardiovascular system. Its connections to the increased incidence of myocardial infarction, stroke, and congestive heart failure were found, as well as the elevated risk of restenosis after coronary artery bypass surgery. Besides, there are data that demonstrate an association between vitamin В12 and telomere length (a marker of aging). This review presents the main reasons of cobalamin deficiency in the elderly, as well as an analysis of clinical studies that show the link between vitamin В12 deficiency and the risk of cardio-vascular diseases and aging process.

107-115 563

Monitoring of the effectiveness of drug therapy is one of the most debated issues in everyday clinical practice. The emergence of new drugs,  methods of analysis, standards, management protocols, and clinical guidelines increases the information load on practitioners and requires a significant investment of time and efforts for self-education. The purpose of the review is to help practitioners in summary form to obtain the necessary information on the issue of control of antiplatelet therapy. The review brings together data  from current  clinical recommendations on antiplatelet therapy in patients with ischemic heart disease, gives information of existing approaches to control of antiplatelet therapy specified in the guidelines and the consensuses of experts. It presents information on the most common modern methods of monitoring of the antiplatelet therapy effectiveness.


116-123 937

According to the World Health Organization, anxiety and depressive disorders will be the second  leading cause of disability by 2020. The review is devoted to the modern concepts of the pathophysiology of depression in patients with ischemic heart  disease (IHD) and to the possibilities of antidepressant therapy. The paper presents analysis of international and domestic researches devoted to efficiency and safety of agomelatine in patients both  with chronic IHD and with unstable angina and acute  myocardial infarction. The review also discusses different points of view, indicating the need for further  studies to evaluate the short and long term effects of antidepressants in patients with IHD in combination with anxiety and depressive disorders.

124-128 728

Current guidelines for the management of atrial fibrillation (AF) recommend using anticoagulants as first-line drugs for stroke prevention, but in real medical practice antiplatelet drugs are often prescribed to elderly patients. Review of clinical and pharmacoepidemiological studies allows us to conclude that  risk associated with acetylsalicylic acid (ASA) use in patients ≥75 years can overweigh its potential benefit. Other antiplatelet drugs are poorly studied in patients with AF. Dual antiplatelet therapy (ASA + clopidogrel) can be prescribed to elderly patients with cardiovascular comorbidity who are deemed unsuitable candidates for anticoagulant therapy for reasons other  than  bleeding risk or those  who refuse to take oral anticoagulants. Combined therapy of antiplatelet drugs with warfarin or new oral anticoagulants results in no reduction in stroke rate compared with anticoagulant monotherapy but is associated with increased risk of bleeding and can’t be recommended.

129-135 988

Russian physicians often afraid to use statins in patients with high cardiovascular risk and nonalcoholic fatty liver disease (NAFLD) or other hepatobiliary diseases, especially in cases when elevated levels of serum transaminases are detected. To expand the use of statins in these patients, a scheme of statins and ursodeoxycholic acid (UDCA) co-administration was developed in 2014 and subsequently in 2016 it was included into the Russian clinical guidelines for the diagnosis and treatment of NAFLD. In addition to the scheme, the guidelines contain the results of clinical trials that demonstrated hepatoprotective, lipid-lowering and anti-atherogenic effects of UDCA in patients with NAFLD. This paper  presents a critical review of these trials, as well as it discusses the points of the scheme, which may contribute to unduly delayed prescribing and insufficiently intensive use of statins in patients with high risk of cardiovascular complications and associated NAFLD.




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