Rational Pharmacotherapy in Cardiology

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Vol 6, No 5 (2010)
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623-630 441

The value of scientific medical information and its impact indicators (researcher’s publishing activity, citation, impact factor, Hirsch index, etc) is considered. Sources of relevant indicators are specified. Data on scientometric indicators of Russian and international scientific cardiology journals are presented.


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Background. Chronic heart failure (CHF) progression is accompanied by remodeling of muscular, collagen and vascular elements of myocardium. This can lead to increase in serum concentrations of myocardial lesion markers (cardiac troponin I (TrI) and myoglobin) which seem to correlate with poor prognosis in patients with CHF.

Aim. To estimate correlations between cardiac TrI, myoglobin, creatine phosphokinase MB-fraction (MB-CPK) serum concentrations and disease severity and prognosis in CHF patients.

Material and methods. Fifty eight patients with CHF of different etiology were included into the study. Physical examination, clinical and biochemical blood assays, chest X-ray study, echocardiography and ECG daily monitoring (initially and at the end of the study) were carried out. TrI and myoglobin levels were estimated by immunoenzymometric assay. The follow-up period was 6 months. The following end points were used: CHF worsening caused hospital admission, acute myocardial infarction, and lethal outcome.

Results. Mean TrI and myoglobin concentrations equaled 0.04 [0.02; 0.06] ng/ml and 62.95 [35.86; 77.28] μg/l, respectively. Demographic characteristics of patients (gender, age) did not influence these markers levels. TrI concentration correlated with CHF severity: it was significantly higher in patients with CHF of functional class (FC) III-IV than in those with CHF of FC I-II (p<0.001). Negative correlation was revealed between TrI level and ejection fraction (p<0.001). TrI concentration was significantly higher in patients with life-threatening ventricular arrhythmia than in patients without it (p=0.001). Besides, TrI level was significantly higher in patients with registered end points than in those with stable CHF course (p=0.001).

Conclusion. TrI correlates with CHF severity and probably has prognostic value in these patients.

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Aim. To study gender and age characteristics of incidence rate, mortality and lethality in acute coronary heart disease (ACHD).

Material and Methods. Analysis of the ACHD (ICD-10 codes: I21.0-I22.9, I20.0, I24) morbidity, mortality and lethality, depending on sex and age was performed in the population (n=285 736; 46% men) of several city administrative districts of Voronezh, Ryazan and Khanty-Mansiysk. Morbidity, mortality and lethality were calculated on the basis of medical documentation as well as cases identified by the study protocol.

Results. The ACHD morbidity and mortality in men were 1.99 and 1.79 times higher (p<0,001), respectively, than these in women. The studied parameters increase with age, reaching a maximum in 50-59 y.o., have a plateau in 60-79 y.o. and then they decrease. Morbidity and mortality in women increase with age, but reach a maximum in 70-79 y.o., being comparable with the male level, and then exceed it in ≥80 y.o. Age curve of lethality in men has J-alike shape with minimum in patients of 50-79 y.o. Women have a line age curve with minimum in patients of <50 y.o.

Conclusion. The population of ACHD patients should be considered according to both the sex and age: <50, 50-79 and ≥80 y.o. Every of these population group has special epidemiological characteristics.

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Aim. To determine indications for differential prescription of beta-blockers in patients with chronic heart failure (CHF) and to study efficacy and safety of beta-blockers therapy.

Material and Methods. Patients (n=90; 55.6% of men; aged 64.7±1.9 y.o.) with CHF class 3-4 NYHA of ischemic and non-ischemic etiology with inadequate treatment with beta-blockers were included in the study. Patients were randomized into 3 groups depending on received beta-blocker: group 1 (n=30) — bisoprolol, group 2 (n=30) — carvedilol, group 3 (n=30) — nebivolol. Study duration was 6 months. Clinical examination (physical, laboratory and instrumental tests) and assessment of the adverse events was performed at baseline and after 6 months. Multiple regression analysis was performed to determine the probability of efficiency achievement by using different parameters (target heart rate, mortality, side effects, hospitalization, 6-minute walk test, left ventricle ejection fraction (LV EF), glomerular filtration rate).

Results. Significant increase in LV EF was found: in group 1 from 32.4±6.1 to 47.2±4.1% (p=0.049); in group 2 from 31.3±8.4 to 46.5±4.2% (p=0.047); in group 3 from 30.3±6.9 to 46.8±4.0% (p=0.043). Class NYHA decreased in group 1 from 3.5±0.5 to 2.3±0.3 (p=0.044); in group 2 from 3.4±0.6 to 2.1±0.2 (p=0.045) and in group 3 from 3.6±0.4 to 2.4±0.4 (p=0.038). The hospitalization rate due to heart failure decompensation was 16.7, 16.7 and 13.3%, respectively. Mortality in groups during 6 months was 6.7, 0.0 and 3.3%, respectively. The efficacy of CHF therapy with betablockers depended on comorbidity and demographic characteristics. The highest refractoriness to CHF therapy was in patients with chronic kidney failure, atrial fibrillation and anemia (odds efficiency was 2.2, 2.9 and 3.1%, respectively). Bisoprolol was the most effective beta-blocker for the CHF patients treatment according to the majority of dependent variables in multiple regression analysis (p=22.13 vs. 20.66 for carvedilol and 18.69 for nebivolol).

Conclusion. A differentiated approach to the beta-blocker prescription depending on the initial clinical and demographic patient characteristics can improve efficacy of the CHF treatment.

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Aim. To study effects of fixed combination of valsartan and amlodipine on of left ventricular hypertrophy (LVH) regression, microalbuminuria reduction and endothelium function in hypertensive patients with metabolic syndrome (MS).

Materials and methods. 20 hypertensive patients (15 females and 5 males) with metabolic syndrome and a history of previous ineffective antihypertensive therapy were studied. Combined antihypertensive therapy was applied during 12-24 weeks. Amlodipine and valsartan dose was 5/160 or 10/160 mg/day depending on blood pressure level. Endothelial function, blood pressure level, urinary albumin excretion and LVH regression were estimated.

Results. Blood pressure reduction to the target level was revealed. There was a significant reduction in microalbuminuria by -55.3±39.2% (р=0.022) in comparison with the baseline. Endothelium-dependent vasodilation increased in 3.6±7.2% (р=0.05) in comparison with baseline, LVH decreased by -9.1±12.4 g/m2 (р=0.021).

Conclusion. Therapy with fixed combination of valsartan and amlodipine results in blood pressure and microalbuminuria reduction, endothelium-dependent vasodilation improvement, LVH regression in hypertensive patients with MS. These findings show that the fixed combination of these antihypertensives has a multifaceted impact on cardiovascular risk.

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Aim. To study the effect of atorvastatin on the rate of atrial fibrillation (AF) recurrence after electrical cardioversion in patients with ischemic heart disease (IHD) and paroxysmal AF.

Material and Methods. Sixty outpatients and inpatients (aged 30-70 y.o.) with IHD and paroxysmal AF were included into the open controlled randomized study immediately after the restoration of sinus rhythm by electrical cardioversion. Patients were randomized into 2 groups. Patients in Group 1 (n=30) received standard therapy recommended for maintenance of sinus rhythm in paroxysmal AF and atorvastatin (average dose 23.5±3.7 mg/day), and patients in Group 2 (n=30) had only the standard therapy. Routine blood analysis, blood chemistry (transaminases, creatine phosphokinase, creatinine, bilirubin, glucose, lipid profile), daily ECG monitoring, treatment safety evaluation were performed. AF relapse was considered as a primary endpoint.

Results. Significant reduction in the rate of AF recurrence in was revealed in patients treated with atorvastatin. According to daily ECG monitoring AF relapse was recorded in 8.3 and 48% of patients in Group 1 and Group 2, respectively (p<0.001). Episodes of sinus tachycardia decreased on 52.3% (p<0.001) and 48,5% (p<0.01) in patients of the 1st and the 2 nd group, respectively.

Conclusion. The addition of atorvastatin to the standard therapy for maintenance of sinus rhythm reduces effectively the rate of AF recurrence in patients with IHD and paroxysmal AF.

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Aim. To study the association of the hereditary sick sinus syndrome (SSS) with gene α2B-adrenergic receptor (ADRA2B) polymorphism.

Material and methods. 29 families with hereditary primary SSS from the database of the Chair of Therapy № 1 of Krasnoyarsk State Medical University named after prof. V.F. Voyno-Yasenetsky were included in the study. Group 1 included probands (20 women and 9 men, 58±0.15 y.o.), group 2 – proband relatives of I, II and III degree (65 males and 68 females, 39±0.13 y.o.), group 3 (control) — 89 healthy volunteers. Clinical examination (physical examination, ECG, bicycle ergometry, ECG monitoring, atropine test, electrophysiological study, echocardiography) was performed in all probands and their relatives. The diagnosis of SSS was confirmed by transesophageal left atrium stimulation in 75 individuals. Genotypic examination of gene ADRA2B I/D polymorphism was performed in 213 individuals: 75 SSS-patients, 49 their healthy relatives, 89 healthy volunteers.

Results. 3 types of ADRA2B genotypes (II — homozygous wild, ID — heterozygous, DD — homozygous mutant) were founded by allele-specific polymerase chain reaction. Significant prevalence of the homozygous genotype of more rare alleles DD in SSS-patients (28±5.2%) compared to the control group (8.99±3.0%) was found.

Conclusion. Study of the genetic marker can be used to identify predisposition to hereditary SSS in the population and individual-family level. SSS due to mutations in genes that regulate cell function of sinus node and the sinoatrial conduct occurs, apparently, extremely rarely.

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Background. More than 100 million adults are exposed to noncardiac surgical interventions every year worldwide, and cardiovascular complications happen in 500 000 - 900 000 patients.

Aim. To evaluate the efficacy and safety of beta-blocker bisoprolol in the perioperative period in hypertensive patients during routine laparoscopic cholecystectomy.

Material and Methods. Hypertensive patients (n=123) scheduled for laparoscopic cholecystectomy were examined. Patients were randomized into 2 groups. Patients of group 1 (n=57) received preoperatively bisoprolol, and patients of group 2 (n=66) had a correction of previously received antihypertensive therapy without beta-blockers addition. Patient examination included traditional preoperative tests as well as ambulatory blood pressure monitoring and echocardiography.

Results. Heart rate was significantly lower in group 1 at admission (66.1±6.9 min-1) and before surgery (61.3±6.1 min-1) than in group 2 (74,5±8,2 and 73,9±7,0 min-1, respectively, p<0,001 for both periods). The preoperative use of bisoprolol in hypertensive patients reduced the hemodynamic stress manifestations. Heart rate was significantly lower in patients of group 1 during intubation (p<0,001) as well as systolic blood pressure was lower during the carboxiperitoneum (p<0,05) and at the end of surgical procedure (p<0,05) compared with patients of group 2. Perioperative complications were registered in 11 (19.3%) patients of group 1 and 25 (37.9%) patients of group 2.

Conclusion. The preoperative (endoscopic cholecystectomy) use of beta-blocker bisoprolol in hypertensive patients reduces hemodynamic manifestations of stress, hospital stay duration and has a good safety profile.


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The main trails proven angiotensin converting enzyme (ACE) inhibitor effects on the life prognosis after myocardial infarction (MI) are described. Different tactics of ACE inhibitors therapy in post MI patients are presented. Approaches to the choice of a specific ACE inhibitor are discussed.

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Mitral valve prolapse (MVP) is a manifestation of the hereditary syndrome of differentiated or undifferentiated connective tissue dysplasia (CTD). Genetic defect of synthesis and/or degradation of extracellular matrix is the basis of the CTD. MVP is a frequent manifestation of CTD and often is its the main manifestation, despite of the involvement of other organs and systems. Micronutrient deficiencies, especially magnesium one is the mostly important in CTD manifestations. Pathogenetic pharmacotherapy should be comprehensive. Magnesium drugs must necessarily be included in the treatment regimen. Analysis of domestic and international study data on magnesium orotate use in patients with MVP is presented. The results of their own experience of the orotate magnesium use and its possible effect on the inotropic cardiac function in patients with MVP are presented.

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Details of the management of patients receiving oral anticoagulants (vitamin K antagonists) for a long time and needed in dental treatment are discussed. Assessment of bleeding and thromboembolism risk in the perioperative continuation or termination of warfarin therapy is shown. Potential of the local hemostatic agents is specified. Modifications of the patient dental health card are offered to prevent complications associated with blood clotting disorders.

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About 150 million men worldwide and about 50% of men aged 40-88 y.o. in outpatient practice suffer from erectile dysfunction (ED). There is a linear relation between the age and ED rate. The main reason of ED in the majority of men (about 80% of patients) is cardiovascular diseases (atherosclerosis, hypertension, diabetes mellitus), as well as certain risk factors (smoking, alcohol abuse, physical inactivity etc.). The problem of ED in cardiac outpatients and modern pharmacotherapy is discussed. The phosphodiesterase-5 (PDE5) inhibitors increase the relaxing effect of nitric oxide and increase cyclic GMP levels during sexual arousal. It results in increase of cavernosum blood flow, contributing to the physiological erection. Three PDE5 inhibitors (sildenafil, tadalafil, vardenafil) are used in clinical practice nowadays.


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Peculiarities of the mode of action and clinical use of fixed low-dose combination of lisinopril and hydrochlorothiazide are discussed. Reasonability of ACE inhibitor and thiazide diuretic combination is supported due to more effective blood pressure control, organoprotection improvement and side events risk reduction. Results of the clinical studies on efficacy and safety of this combination in hypertensive patients with different concomitant diseases are presented.

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Data about efficacy and safety of long-term therapy with acetylsalicylic acid in patients with cardiovascular diseases are presented. The main practical ways to reduce the possible gastrointestinal complications of the treatment are discussed.

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The possible indications for the choice of two component antihypertensives combinations are presented. The advantages of ACE inhibitor+calcium channel blocker combination are shown in terms of antihypertensive efficacy, organoprotective properties, and positive metabolic effects. Clinical aspects of ACE inhibitor+thiazide diuretic combination usage, its possible side effects and ways to minimize them are considered.

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Role of magnesium and potassium deficiency in the development of cardiovascular diseases and their complications is discussed. Results of studies on efficacy of magnesium and potassium drugs in cardiology practice are presented. Preventive role of potassium and magnesium in the progression of atherosclerosis, arterial hypertension, endothelial dysfunction and insulin resistance is shown. The advantages of combined magnesium and potassium drugs are shown.


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Key positions of Guidelines on the prevention, diagnosis, and treatment of infective endocarditis issued by the Task Force of ESC in 2009 are explained in the comments. Recent opinions on these items are presented.


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News about Congress of the European Society of Cardiology 2010 in Stockholm is presented. The main significant events of the Congress are discussed. Symposia on antiplatelet therapy, hypertension, and recently completed research results are highlighted.


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5 years with Rational Pharmacotherapy in Cardiology.

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To the jubilee of Veronica I. Skvortsova, Honoured Science Worker, corresponding member of Russian Academy of Medical Sciences, Deputy Minister of Health and Social Development Ministry.

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To the 90-th anniversary of the birth of Fedor I. Komarov.

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