Rational Pharmacotherapy in Cardiology

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Vol 5, No 1 (2009)
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5 371

In this Issue.


6-11 579

Aim. To assess the efficacy of specialized management of pregnant women with cardiovascular diseases (CVD) in the Udmurt Republic (UR) of Russia.

Material and methods. In prospective and retrospective study we investigated pregnancy outcomes in all 17948 women in management system created for pregnant patients with CVD in the UR from 2000 to 2007. The system comprises specialized outpatient and inpatient departments and an obstetric hospital within the regional cardiological centre. Pregnant women had different CVD including hypertension, congenital and rheumatic heart disease, cardiac arrhythmias, noncoronary myocardial disease, disorders and autoimmune diseases of connective tissue, etc.

Results. Perinatal mortality decreased by 41,1% from 11,2‰ in 2000 to 6,6‰ in 2007. During 8 years, no one woman died.

Conclusion. The management system for pregnant women with CVD within the regional cardiological clinic makes it possible to reduce of maternal and perinatal mortality rates significantly. 


12-22 742

Aim. To estimate the prevalence of burnout in primary care physicians and its influence on medical practice stereotypes and on clinical inertia.

Material and Methods. The anonymous single-stage poll was carried out among 184 primary care physicians. The questionnaire included information about sex, age, period and conditions of work, established stereotypes of practices. Burnout was evaluated by Russian analog of Maslach Burnout Inventory. It was defined in high level of emotional exhaustion and depersonalization and low level of personal accomplishment 11 questions were developed to reveal of suboptimal medical practice (for example, “I do not discuss treatment options with patient and do not give full answers to his questions” or “I make diagnostic and treatment errors despite of my professional knowledge and inexperience”).

Results. The burnout syndrome (or extreme grade of emotional burnout) occurs in 13,1% and high level of emotional burnout – in 49,7% of primary care physicians. Features of suboptimal medical practice are usually found in 24,2% of primary care physicians at least monthly. It expresses more often in improper attitude to paqtients and their problems associated with a disease. Thus, burnout contributes to improper attitude to patients. Professional burnout affects established work stereotypes and can promote development of physician’s clinical inertia.

Conclusion. As the burnout is common among primary care physicians, an adequate monitoring and prevention of this state is necessary in medical labour management.

23-27 670

Aim. To evaluate antihypertensive and metabolic effects of the therapy based on carvedilol (C) in comparison with metoprolol (M) in hypertensive patients with overweight or obesity.

Material and methods. 320 patients were involved in multicenter, randomized open parallel study. One part of the patients received C 12,5 mg BID (Vedicardol, “Sintez”), another part – M 25 mg/day BID. Doubling dose of β-blockers (BB) and switching patients to combined therapy with AML 5-10 mg OD (Amlorus, “Sintez”) and hydrochlorothiazide (HCT) 12,5-25 mg OD was performed if necessary. The study duration was 24 weeks.

Results. Significant reduction of systolic and diastolic blood pressure was revealed in both groups, there was no difference between groups (р=0,88 and p=0,61 respectively). Switching patients to combined therapy with AML and HCT was made more often in M group than in C group (p>0,05). Prescription of BB resulted in significant reduction of the heart rate, there was no difference between groups (p=0,61). 96,2% patients of group C and 95,5% of group M reached target levels of BP. Significant reduction of glucose (p<0,01) and uric acid levels were registered in group C as well as tendency to lowering of total cholesterol (TC) and low density lipoprotein cholesterol (LDLC) levels. 34 adverse effects were registered during observation period: 24 in group C and 10 in group M (p>0.05), half of them were not related to BB taking.

Conclusion: Controlled antihypertensive therapy, based on С and M, allows reaching target levels of BP in majority of patients with overweight or obesity. Switching to combined therapy was made more seldom in group of С than in M group. Both drugs demonstrated metabolic neutrality, however significant lowering of glucose and uric acid levels and tendency to lowering of TC an LDLC levels was observed only in group С.

28-32 14601

Aim. To compare antihypertensive effect of ramipril monotherapy at morning and evening taking.

Material and methods. 22 patients (10 men, 12 women; aged 62,1±1,9 y.o.) with arterial hypertension of 1-2 stage were involved into the open randomized crossover study. Patients were randomized into 2 groups depending on ramipril taking time (morning or evening). Ambulatory blood pressure (BP) monitoring (ABPM) was performed. Patients of both groups were comparable in basic clinical characteristics and initial ABPM indices. Analysis of peak and phase characteristics of 24 hour BP profile was used as well as standard evaluation. Treatment duration was 3 weeks. Ramipril dose titration was made in 1,5 weeks. The average daily dose of ramipril was 6,1 mg in the morning taking, and 5,0 mg in the evening taking.

Results. 20 patients finished study completely. 24 hour initial level of systolic (SBP) and diastolic BP (DBP) was 141,5±1,6/85,3±1,1 mm Hg. After ramipril monotherapy with evening taking BP reduced to 132,6±1,6/79,8±1,1 mm Hg (p<0,001) and with morning taking – to 131,8±1,6/79,2±1,1 mm Hg (p<0,001). Evening ramipril taking led to significant improvement of 24 hour BP profile. Night SBP/DBP reduction became deeper from 7,7±1,2/11,5±1,3% to 12,5±1,2/19,1±1,3 % (p<0,01). Morning taking did not have significant influence on these indices. Ramipril did not result in clinically significant hypotension including night one.

Conclusion. Evening ramipril taking is effective and safe. It can be recommended to patients with insufficient night BP dipping (non dippers). 

33-36 810

Aim. To find echocardiographic indicators of heart remodelling that improve estimation of heart failure (HF) severity. To evaluate sensitivity of laboratory markers of HF, brain (BNP) and atrial (ANP) natriuretic peptides, in patients with mitral heart diseases of rheumatic aetiology.

Material and methods. 100 patients with rheumatic mitral disease and chronic HF (CHF) of I-IV class (NYHA) were examined. Echocardiography was performed in all patients with evaluation of the standard indices to define disease severity. Indices of sphericity, myocardial stress of the left ventricle, etc were also evaluated. BNP and ANB levels were assessed by enzyme immunoassay method.

Results. CHF severity had the strongest correlations with atrial sizes, left atrial systolic function and level of pulmonary hypertension. Moderate increase of BNP level in severe CHF (III-IV class) and its rare increase in mild CHF (I-II class) were detected. Significant changes of ANP level were not found. Moderate correlation of BNP level with myocardium mass index, level of pulmonary hypertension and mitral regurgitation was detected.

Conclusion. Intensity of heart remodelling in rheumatic mitral diseases is mainly determined by the left atrial area, left atrial systolic function, mitral orifice size, levels of mitral regurgitation and pulmonary hypertension, size and ejection fraction of right ventricle. Normal BNP level does not confirm an absence of CHF or negative prognosis in patients with rheumatic heart disease.

37-41 507

Aim. To study efficacy of testosterone undecanoate (TU) therapy in men with stable angina and androgen deficiency.

Material and methods. The serum testosterone level was detected in 247 men (aged 51,6±1,8 y.o.) with stable effort angina. 60 patients with androgen deficiency additionally to basic angina therapy received TU (120-160 mg daily). 54 patients with androgen deficiency (control group) received only basic angina therapy. Dynamics of clinical and ECG manifestations of myocardial ischemia and quality of life (QOL) parameters was studied.

Results. Androgen deficiency is revealed in 114 (46,2%) of patients. Therapy with TU during 3 months resulted in reduction of angina attacks and extent of myocardial ischemia (according to Holter ECG monitoring and stress test) as well as QOL improvement.

Conclusion. Androgen deficiency is observed in 46,2% of men with stable angina. TU increases of antianginal therapy efficacy, improves QOL and is well tolerated. 

42-45 760

Aim. To study the myocardial remodeling features in patients with stable angina depending on disease severity and experienced myocardial infarction (MI).

Material and methods. 148 male patients with stable angina were examined and randomized into 3 groups (G1-G3). 52 patients of G1 had angina of I-II functional class (FC). 49 patients of G2 had angina of III FC, and 47 patients of G3 had angina of IV FC. History of MI had 79,5, 87.2 and 92.6% of patients in G1, G2 and G3 respectively. 35 healthy men were included into control group. Coronarography, bicycle ergometry and 24-hour ECG monitoring was performed. Left ventricular (LV) function and remodeling was assessed with echocardiography.

Results. G3 patients had LV eccentric hypertrophy as a result of postinfarction cardiosclerosis which accompanied with LV systolic dysfunction, a myocardial stress increasing and LV spherification. G1 patients had no any significant disorders of LV systolic function.

Conclusion. Severe ischemic heart disease is associated with a dysadaptive remodeling unlike mild ischemic heart disease, which is associated with an adaptive myocardial remodeling.

46-50 518

Aim. To evaluate the relationship of 24-hour blood pressure (BP) monitoring data with myocardial mass and type of left ventricle hypertrophy (LVH) in non-treated patients with essential hypertension (HT).

Patients and methods. We reviewed echocardiograms and BP monitoring data of 500 patients (250 females and 250 males; aged 53,1±12,2 y.o.).

Results. Normal geometry of left ventricle (LV) was found in 143 patients (28,6%), concentric remodeling of LV – in 73 (14,6%), concentric LVH - in 138 (27,6%) and eccentric LVH – in 146 patients (29,2%). The least disturbances of 24-hour BP profile were observed in patients with normal LV geometry; 60,1% of patients had normal reduction of night BP. More than a third of patients had disturbances of circadian BP profile. Mostly severe disturbances of 24-hour BP profile were observed in patients with concentric and eccentric LVH. Circadian BP disturbances were revealed in two thirds of patients. Inadequate night BP reduction and inverted type of circadian BP profile predominated. Negative correlation between 24-hour systolic BP index and LV myocardial mass index was observed. Some LV structural disturbances as well as systolic dysfunction were revealed in patients with LV concentric remodeling. Besides HT of 3 grade and excessive night BP reduction were observed more often in these patients.

Conclusion. The relationships between LV structural disturbances and 24-hour BP profile allow to reveal patients with unfavorable course of HT.

51-56 617

Aim. To evaluate possibility of complex pharmaceutical effect simultaneously on 2 risk factors – arterial hypertension (HT) and hypercholesterolemia (HH) in patients with high risk of cardiovascular complications (CVC).

Material and methods. 101 patients with HT of 1-2 stage, HH and high risk of CVC (SCORE>5) were included in the study. Patients were randomized in 2 groups: active therapy group (ATG) and control group (CG). ATG patients were actively treated for HT and HH control. The long-acting nifedipine (Nifecard XL, LEK) 30 mg once daily (OD) was prescribed as start antihypertensive drug. Hydrochlorothiazide 12,5 mg/day OD and bisiprolol 5 mg OD was added if antihypertensive effect was insufficient. Atorvastatin (Tulip, LEK) 20-40 mg OD was prescribed for HH control. Management of CG patients was performed by doctors of out-patient clinics. The study duration was 12 weeks.

Results. Systolic and diastolic blood pressure (BP) levels in ATG patients were lower than these in CG patients. Target BP level was reached in 88,4% of ATG patients and only in 48,9% of CG patients. Cholesterol of low density lipoprotein (CH LPLD) level was also lower in ATG patients than this in CG patients. Target CH LPLD level was reached in 37,2 % of ATG patients and in 8,3 % of CG patients. Relative risk of CVC was significantly lower in ATG patients than this in CG patients.

Conclusion. SAFARI trial shows that effective pharmaceutical simultaneous control of 2 key risk factors, HT and HH, results in risk reduction of CVC.


57-62 1038

Approaches to the choice of antihypertensive pharmacotherapy are discussed. Evidence base of ACE inhibitor lisinopril is surveyed. Data about lisinopril effects on different endpoints, organoprotective action and advantages over other ACE inhibitors are presented. 

63-68 760

The main differences between original and generic drugs as well as registration criteria for generics are described. Possible reasons of discrepancy in bioequivalence and therapeutic equivalence of original and generic drugs are reviewed. The examples of such a discrepancy as a result of comparative clinical trails (enalapril maleate) are discussed. Approaches to planning of comparative trails on drug therapeutic equivalence are presented. 

69-72 561

Aim. To study changes of intercellular cooperation in peripheral blood induced by treatment in patients with arterial hypertension (HT), ischemic heart disease (IHD) and chronic heart failure (CHF).

Material and methods. 610 patients were involved into the study, including 250 patients with HT of stages I-III (50 untreated patients), 150 patients with IHD and 210 patients with CHF of stages I-III. All patients were treated except 50 hypertensive ones. 80 healthy patients (40 men, 40 women) were included into control group. Blood smears of patients were evaluated (Romanovsky's stain). A number of leukocyte, autorosettes and autorosettes with erythrocyte lysis was calculated. The cellular association consisting of a neutrophil, monocyte or eosinocyte with 3 or more erythrocytes skintight to their surface defined as autorosettes. Erythrocytes number and hemoglobin level determined in peripheral blood.

Results. Single autorosettes in peripheral blood were observed in patients of control group and in untreated patients with HT. Treated patients with HT, IHD and CHF had increased number of autorossets and autorosettes with erythrocytes lysis. This phenomenon resulted in reduction of erythrocytes number and hemoglobin level in peripheral blood.

Conclusion. Treated patients with cardiologic diseases had changes in intercellular cooperation. It should be considered at intensive and long term therapy.

73-76 524

Aim. To study morphologic changes in myocardium of Wistar rats caused by single and long term dopamine administration.

Methods. In acute study dopamine 10 mkg/kg was administrated to 15 rats by a single intraperitoneal injection. The material was taken in 2, 6, 24 hours and in 1 month after drug administration. In chronic study dopamine 10 mkg/kg was administrated to 15 rats 3 times a day by intraperitoneal injections during 2 weeks. The material was taken just after the drug administration was stopped and in 1 month of animals keeping without stress and drug influences. Control group included 15 rats comparable with experimental animals in age and weight. They were keeped without stress and drug influences. Morphometric parameters of left and right ventricles were evaluated as well as density of cardiomyocytes, collagen, vessels and volume of extracellular space.

Results. The enlargement of cardiac fibrosis is found both in acute, and in chronic study. In acute study cardiac fibrosis was located mainly in a right ventricle. In chronic study cardiac fibrosis was located in both ventricles, but also mainly in a right one.

Conclusion. Significant morphological «asynchronism» of the left and right ventricles remodeling requires elaboration of methods of myocardium protection and cardiac function control during dopamine administration. 


77-82 2169

Aim. To estimate heart rate variability (HRV) from 5-min and 24-h electrocardiogram (ECG) recordings in female patients with rheumatoid arthritis (RA) and patients of control group, to analyze association between HRV indexes and cardiovascular risk factors and RA-related clinical characteristics.

Material and Methods. 90 female patients with RA and 30 healthy subjects matching for age were included in the study. The baseline evaluation included a physical examination, assessment of the cardiovascular risk factors and RA clinical characteristics, laboratory tests, 5-min and 24-hour ECG recordings. We analyzed the time-domain (SDNN, rMSSD, pNN50), frequency-domain (LF, HF, LF/HF ratio) and nonlinear indexes (SD1, SD2, SD21) of HRV from 5-min ECG recording and the time-domain (SDNN, rMSSD, pNN50) indexes from 24-h ECG recordings.

Results. Patients with RA had lower HRV in comparison with control subjects (p<0,05). We got the following results for 5-min ECG recordings: time-domain (SDNN, rMSSD, pNN50), frequency-domain (LF, HF) and nonlinear indexes (SD1, SD2) negatively correlated with erythrocyte sedimentation rate (ESR) (р<0,05). All parameters of HRV (except for pNN50) strongly negatively correlated with disease activity score (DAS28). LF and HF levels depended on age. The analysis of 24-h ECG recordings showed negative correlation of timedomain indexes (SDNN, rMSSD, pNN50) with DAS28 and ESR.

Conclusion. Reduced HRV is associated with inflammation activity in patient with RA. Low level of HRV and high RA activity are unfavorable cardiovascular factors.


83-86 493

The role of beta-blockers (BB) in arterial hypertension therapy is discussed from the evidence based medicine point of view and according to international guidelines. Data of the latest meta-analysis comparing effects of BB and other antihypertensive drugs on a probability of cardio-vascular complications are presented. 

87-95 592

Data on atrial fibrillation (AF) epidemiology and AF influence on the risk of cardiovascular complications are presented. Principles and tactics of AF therapy are discussed in accordance to evidence based medicine and European society of cardiology Guidelines. Algorithms for choice (on the basis of risk stratification) of different antiarrhythmic drugs and anticoagulants are described. Perspectives in improvement of efficacy and safety of AF therapy are reviewed. 


112-113 494

New definitions of myocardial infarctions (comments on “Universal definitions of myocardial infarction” published in №5, 2008) 

115-116 413

Information letter about National Congress of Cardiology, 6-8 October, 2009.

117 414

Report on the holding of XI All-Russian scientific and educational forum “Cardiology 2009”.

117-118 403

Expert Council of annual National Award “Purple heart” started considering applications.

119 379

Up to date information for leading cardiologists and therapeutists about latest prevention and therapy methods reduces growth rate of cardiovascular diseases.

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