Rational Pharmacotherapy in Cardiology

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Vol 4, No 4 (2008)



6-11 476

Aim. To study pathogenetic mechanisms and cardiovascular risk factors prospective cohort study in liquidators of consequences of Chernobyl Nuclear Disaster 13-20 years after an accident.

Material and methods. 409 irradiated patients and 224 control patients comparable on the age and gender were involved into two-stage cohort prospective study with 4,5years period of observation. Database included results of standard questionnaires, social and demographic description, education, family status, smoking and alcohol habits, anthropometry, fasting lipids and glucose, blood pressure, ECG, arrhythmias on ECG monitoring, heart rhythm variability, Echocardiography, thyroid ultrasound image, spirometry, transesophageal electrophysiological study of heart conduction system, exercise tests, functional class of ischemic heart disease, stage of arterial hypertension, fatal/nonfatal end-points, as well as neurologist, endocrinologist and cardiologist conclusions. Totally 267 variables were included in the analysis.

Results. Spectrum of active cardiovascular risk factors in cohort of irradiated patients was entirely different from this in control patients. Determinative value for irradiated patients was related with night hypersympathetic activity, ANDS syndrome (Autonomic Nervous Dysfunction on hyperSympathetic type) and less related with decreased airway conductance in small bronchial tubes.

Conclusion. Comparative prospective cohort study in liquidators of consequences of Chernobyl Nuclear Disaster 13-20 years after an accident revealed highly significant new and permanently acting cardiovascular risk factors. These data let to work out appropriate approaches to therapy and prevention of cardiovascular diseases.

12-17 758

Aim. To develop a test on tolerability of small alcohol doses (SAD), to study hemodynamic and vestibular changes induced by SAD during mono- and combined antihypertensive therapy.

Material and methods. 30 healthy volunteers and 292 patients with arterial hypertension 1-2 stages were involved in the study. Tolerance to SAD was estimated in untreated hypertensive patients (n=77), patients receiving one (n=218), two (n=46) and three (n=28) antihypertensive drugs. Tolerance to SAD was evaluated by blood pressure changes as well as change of upright body balance and subjective sensations of the patient.

Results. Hypotension and circulatory vestibular disorders can be induced by alcohol consumption during antihypertensive therapy. These disorders appear more often due to peripheral vasodilators as well as combined antihypertensive therapy.

Conclusion. It is necessary to inform the patient about risk of alcohol taking and necessity to restrict of its dose during antihypertensive therapy.

18-22 488

Aim. To study effect of 12-month therapy with lovastatin on vascular remodeling, systolic and diastolic functions of left ventricle (LV).

Material and methods. 84 patients (54,3±6,5 y.o.) with ischemic heart disease (IHD) and dislipoproteinemia were involved in the study. Patients were randomized into 2 groups. Patients of the 1st group (n=44) received lovastatin (20-60 mg daily) in addition to hypolipidemic diet and standard therapy. Patients of the 2nd group (n=39) were treated with diet and standard therapy only. Lipid spectrum and transaminase blood levels estimation, carotid duplex ultrasonography, echocardiography were performed initially and after 12 months of treatment.

Results. Decrease of carotid intima-media thickness, delay of increasing of LV myocardium mass index, increase of LV ejection fraction was observed in 12 months of treatment in patients of the 1st group. There were not any changes of LV diastolic function in both groups.

The conclusion. In patients with IHD and dislipoproteinemia 12 month lovastatin therapy prevents of vascular remodeling and improves LV systolic function.

23-27 596

Aim. To assess the role of endothelial vasodilating, vasoconstrictive and adhesive dysfunction in the development of angina pectoris (AP) in patients with ischemic heart disease (IHD).

Material and methods. 83 patients with IHD were included in the study. 30 patients had AP of functional class (FC)-II, 27 patients - FC-III and 26 patients - FC-IV. The control group consisted of 25 healthy persons. Bicycle ergometry, daily ECG monitoring and echocardiography were used for verification of IHD. Endothelial vasodilating function was assessed by endothelium-dependent (EDVD) and endothelium-independent vasodilatation (EIDVD) of brachial artery. Vasoconstrictive function was assessed by the level of endothelin (ET-1). Endothelial adhesive function was evaluated by plasma concentration of intracellular adhesion molecules – JCAM-1, VCAM-1 and Е-selectin.

Results. Normal EDVD and EIDVD were observed in patients with AP of FC-II. The more severe FC of AP the more prominent endothelial vasodilating dysfunction was revealed as well as the higher levels of ET-1 and intracellular adhesion molecules. Patients with AP of FC-IV had hyperexpression of JCAM-1, VCAM-1, Е-selectin and ET-1 and low levels of EDVD and EIDVD.

Conclusion. Progression of IHD related with growing endothelial vasodilating, vasoconstrictive and adhesive dysfunction.

28-31 509

Aim. To study clinical and epidemiological features of arterial hypertension (HT) combined with abdominal obesity (AO) and pharmacological correction of left ventricle myocardium structural and functional disorders.

Material and methods. Single-stage epidemiological study was conducted in Novgorod region population (n=4840). All patients with HT were revealed and analyzed depending on age and gender. Patients with HT grade 2 were split in two groups. 124 women (aged 49,36±1,2 y.o.) and 126 men (aged 50,15±1,8 y.o.) with HT and AO were included in the first group. 127 women (aged 50,05±1,7 y.o.) and 125 men (aged 49,61±1,6 y.o.) with HT and normal body mass index were included in the second group. Anthropometric and echocardiography examination was performed before and after 1, 3 and 6 months of therapy (metoprolol, nebivolol, amlodipine, lisinopril).

Results. High prevalence of HT was revealed: 44,4% in men and 48,7% in women. AO was observed 5,4 times more often in women than this in men (18,5% and 3,4%, respectively, р<0,001). Combination of HT and AO was also revealed 5,3 times more often in women than this in men (14,3% and 2,7%, respectively, р<0,001). AO in patients with HT contributes to development of left ventricle concentric hypertrophy and diastolic dysfunction.

Conclusion. Antihypertensive therapy does not prevent left ventricle hypertrophy and diastolic dysfunction in hypertensive patients with AO.

32-35 962

Aim. To study effect of combination of verapamil retard (Isoptinum SR) with indapamide retard (Arifon retard) on blood pressure (BP) level as well as lipid profile, glucose and electrolytes serum level in patients with metabolic syndrome (MS).

Material and methods. 20 women of 35-65 y.o. with MS were examined. The combination of verapamil retard and indapamide retard were prescribed to patients during 24 weeks. Ambulatory BP monitoring (ABPM), lipide profile tests, electrolytes and glucose serum level tests were performed in all patients initially and after treatment.

Results. Target systolic BP (SBP) was achieved in 90% of patients. Target diastolic BP (DBP) was achieved in 75% of patients. Drug combination effectively reduced SBP, DBP and pulse BP levels and improved other BP indices. This drug combination did not affect BP profile as well as glucose and electrolytes serum level, lipid profile.

Conclusion. High antihypertensive efficacy and metabolic neutrality of verapamil retard and indapamide retard allows to use this combination in patients with MS.


36-39 395
Many generic medicines appear in the pharmaceutical market now. However, they are not always completely comparable with original drugs on efficacy and safety. In this article pharmacoeconomical estimation of some generics and original drugs was performed on example of therapeutic equivalency studies.
40-46 475

Aim. To compare different strategies of start antihypertensive therapy in out-patients.

Material and methods. 120 out-patients with arterial hypertension (HT) 1-2 stages were included in the study and randomized in 3 groups. Patients of group «A» received start treatment in compliance with age, clinical features and mechanisms of hypertension. Patients of group «B» received step-by-step start antihypertensive therapy based on doses titration and addition of the second (third) drug if necessary. Patients of group «C» received fixed drug combination with addition of other antihypertensive medicines if necessary. Decrease of BP level and number of visits were used as criteria of therapy efficacy. Pharmacoeconomic analysis of antihypertensive therapy was done in all groups.

Results. Strategy of HT start therapy in group «C» had advantages in speed of blood pressure normalization, number of necessary visits and in pharmacoeconomic efficacy in comparison with the strategies in group «A» and «B».

Conclusion. HT start therapy with implementation of fixed low dose combination leads to the best result in comparison with other strategy based on step-by-step drug replacement (as well as their combining) or monotherapy dose titration.


47-53 598

Aim. To study the efficacy and safety of reversible MAO inhibitor pirlindol (Pyrazidol) in elderly post infarction patients with chronic heart failure (CHF) and affective disorders.

Material and methods. 60 patients with CHF of II-III NYHA class 3-4 weeks after myocardial infarction with and anxious and depressive disorders were involved into the study. The patients were randomized in two groups. Patients of the first group received standard therapy (bisoprolol, lizinopril, simvastatin, acetylsalicylic acid, nitrates and diuretcs as required) in combination with pirlindol for 12 weeks. Patients of the second group received standard therapy alone. The follow-up period was 6 months. At baseline and after 12 and 24 weeks of therapy psychosomatic status was examined with the Beck questionnaire and HADS scale. Quality of life (QoL) survey with the Minnesota, Seattle and MOS SF- 36 questionnaires were performed as well as ECG with assessment of heart rate variability (HRV) and echocardiography.

Results. Pirlindol improved QoL and was effective in correction of anxious and depressive disorders in CHF patients. At the end of the follow-up period normal Beck scores were registered in 90% and mild depression scores - in 10% of patients in pirlindol group. At the same time all patients of control group had depressive disorders of different intensity. Significant increase of left ventricular ejection fraction was observed in pirlindol group vs control group (20,9 vs -2,5%). Heart morphometric parameters improved in both groups, but left ventricle size reduction was more prominent in pirlindol group (-10,69 vs -5,34%). According to the spectral and time indexes of HRV, pirlindol treatment led to normalization of autonomic balance. Sympathetic overdrive was observed in patients of the control group.

Conclusion. In elderly patients with CHF after myocardial infarction pirlindol taken additionally to the standard therapy is well tolerated, effectively eliminate psychosomatic disorders, results in significant improvement of morphofunctional cardiac condition and decrease of sympathetic over activity. Pirlindol can be recommended for the management of mild and moderate depressive disorders in elderly patients with CHF.

54-58 693

Aim. To study efficacy and tolerability of antihypertensive therapy with enalapril (Berlipril®, Berlin-Chemie AG/Menarini Group) and diltiazem (Altiazem® PP, Berlin-Chemie AG/Menarini Group) in postmenopausal women with arterial hypertension (HT) and climacteric disorders.

Material and methods. 60 postmenopausal women (aged 56,8±3,9 y.o.) with HT of 1-3 degrees were included into the study. They were split in two groups. Patients of the first group (30 people) received enalapril (Berlipril®) 20 mg/daily, patients of the second group (30 people) – diltiazem (Altiazem® PP) 180-360 mg/daily. Observation period was 6 months. Ambulatory blood pressure monitoring (ABPM) was performed before treatment and after 3 weeks, 1, 3 and 6 months of therapy. Climacteric syndrome severity and urodynamic disorders was estimated as well as psychic status according to score of depression and anxiety.

Results. Office and ambulance blood pressure decreased after 6 months of therapy in all patients of both groups. A number of complaints on headache and giddiness reduced significantly. Severity of climacteric syndrome also decreased. Enalapril (Berlipril®) monotherapy and especially combined therapy with hydrochlorothiazide led to aggravation of urodinamic disorders. On the contrary both monotherapy with diltiazem (Altiazem® PP) or its combination with hydrochlorothiazide had positive effect on urodinamics. Both therapies reduced depression and anxiety levels significantly.

Conclusion. All spectrum of pharmacology effects should be taken into account during antihypertensive therapy of patients with climacteric disorders.

59-64 2051

Aim. To study effects of Ginkgo biloba based drug (Memoplant, Dr Willar Schwabe, Germany) on haemorheological and clinical status in elderly patients with circulatory encephalopathy and controlled arterial hypertension.

Material and methods. 80 patients (>60 y.o.) were involved in the study. Patients were randomized (3:1) on Memoplant (240 mg/daily) treatment group and control group. Duration of observation was 16 weeks. The changes of neurological complaints, neuropsychological and life quality test results were estimated during the study. The rheological indicators (blood, plasma and erythrocyte suspension viscosity; aggregative activity and plasticity of erythrocytes) also were studied.

Results. Reduction (by 50-90%) of neurological complaints (headache, giddiness, tinnitus, unsteadiness walking) were founded in patients receiving Memoplant. Cognitive abilities according to mental status scale, frontal tests battery, 5 words test, watch drawing test and quality of a life according to QOLI-NS scale improved in patients treated with Memoplant. Decrease of blood viscosity (by 19,3%, р<0,01) , erythrocytes rigidity index (by 15,6%, р<0,05) and erythrocyte aggregation (degree of aggregation by 45,6%; average aggregate size by 25,9%, р<0,05) > <0,05) was observed. Tissue oxygen supply was increased by 23,3% (р<0,05) in comparison with initial state. Changes of haemorheological indicators were not founded in control group.

Conclusion. Memoplant increases brain oxygenation due to improvement of microcirculatory blood flow.

65-68 5290
A number of comorbid patients is increasing significantly. Chronic diffusive liver diseases meet at 40 % of patients with hypertension. Lisinopril advantages in patients with hypertension and diffusive liver diseases are shown in the article on example of concrete study.


69-75 482
Angiotensin II receptor antagonists (ARA) established their position recently duet to new indications above arterial hypertension (HT). These are chronic heart failure, history of myocardial infarction, atrial fibrillation and metabolic syndrome. Analysis of evidence basis, including recently published biggest international clinical studies, was performed in the article. Data demonstrate that ARA can be effectively and safely used in wide clinical practice for improvement of life quality and life prolongation in patients with HT.
76-79 488
Cardiovascular event risk reduction with medicines is discussed in the article. The role of randomized controlled trials is emphasized for estimation of therapy effects.
80-84 1066
Estimation of cardiovascular risk is discussed. Serum lipoproteins, glucose, fibrinogen, von Willebrand factor, tissue-type plasminogen activator, C-reactive protein etc are offered for use as laboratory indicators. At the same time new markers of high cardiovascular risk are under development. D-dimer is a product of fibrin degradation and its plasma level reflects intensity of intravascular thrombosis and fibrinolysis. Plasma level of D-dimer as a tool for estimation of cardiovascular risk and pharmacotherapy efficacy is discussed.
85-89 459
Usage of β-blockers (BB) for treatment of patients with cardiovascular diseases is discussed. Results of the basic clinical trials with BB (LIFE, ASCOT, etc.) are analyzed. The role of sympathetic system in different stages of cardiovascular continuum as well as forecast of BB clinical efficacy is surveyed. Author presents a review of data about selective β1-blocker, metoprolol succinate (Betalok ZОК), in patients with cardiovascular diseases.


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ISSN 2225-3653 (Online)