Rational Pharmacotherapy in Cardiology

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Vol 4, No 5 (2008)



6-10 336

Aim. To study results of registration, calculation and evaluation of quality of arterial hypertension (HT) control (HT Register) in Vologda Region (VR).

Material and methods. HT Register system is developed and legislatively introduced in the VR. Blood pressure registration in every visitor of out-patient clinics is the basic principle of HT Register. The algorithm of HT diagnosis in primary medical care of rural public health services was developed. Analysis of results of HT Register implementation in VR during 2004-2007 is presented.

Results. Patients with HT stage 1 seek medical help more often in cities while patients with HT stage 3 seek medical help more often in villages. Patients with HT in villages take antihypertensive drugs more often, but they have more risk factors and associate conditions.

Conclusion. Improvement of HT pharmacotherapy was observed in urban and rural districts of VR. At the same time non pharmacologic HT control has to be developed.


11-15 331

Aim. To assess cognitive functions in liquidators of Chernobyl accident (LCA) consequences suffering from arterial hypertension (HT) and to study efficacy of their treatment with cortexin (complex of polypeptide fractions).

Material and methods. 60 men (aged of 39-60 y.o.), LCA with HT and cognitive disorders were included in the study. Cortexin was used (10 mg intramusculary during 10 days) for one or two courses. Efficacy of treatment was estimated by neuropsychological tests (Shulte test , A.R. Lurija test, serial account, test "feeling, activity, mood", headache intensity on VAS scale) before and in 10 days of treatment as well as 6 and 12 months after treatment.

Results. Cortexin therapy (2 courses) increased of mental processes speed and retention of information volume, reduced personal and behavioral disorders.

Conclusion. Treatment with cortexin (2 courses) improves cognitive functions in LCA with HT.

16-22 1247

Aim. To study adjuvant effect of betahistine dihydrochloride to ACE inhibitors in patients with chronic heart failure (CHF) class II-III suffering from giddiness.

Material and methods. 61 patients with CHF class II-III, ejection fraction ≤45% (Simpson) suffering from giddiness were involved into randomized open parallel study. Patients were randomized to Betahistine dihydrochloride plus basic CHF therapy or only basic therapy groups. Enalapril dose titration was performed in all patients. Quality of life and giddiness severity evaluation, electrocardiogram was performed initially and after treatment. Clinical examination results, drug therapy and adverse event were registered at each visit.

Results. The target ACE inhibitor dose (≥20 mg daily) was reached in 97 % of patients. It led to significant reduction of dyspnea, edemas, CHF class reduction and life quality increase. Significant differences between investigated groups were not found. Reduction of giddiness severity was shown in both groups. There was a trend to more prominent improvement of life quality (р=0,08) and more frequent achievement of target ACE inhibitor dose in patients treated with betahistine dihydrochloride.

Conclusion. The target ACE inhibitor dose can be achieved more than in 90% of patients with CHF class II-III without hypotension symptoms. Adjuvant usage of betahistine dihydrochloride is necessary in patients with CHF still suffering from giddiness after achievement of target ACE inhibitor dose.

23-27 537

Aim. To assess efficacy and safety of generic simvastatin, Simvahexal, in comparison with original drug of simvastatin, Zocor, in patients with hyperlipidaemia in short-term study.

Material and methods. 30 patients (19 men and 11 women, 64,0±1,8 y.o.) with low density lipoprotein (LDL) cholesterol ≥3,0 mmol/l and high cardiovascular risk were involved into the study. During 5 weeks before study including patients kept the hypolipidaemic diet and did not receive any hypolipidaemic drug. 28 patients completed study, 2 patients drop out: one patient because of nettle rash on Zocor therapy, another one – because of personal reason. Efficacy was assessed by dynamic of lipid profile and a number of patients who reached target level of LDL cholesterol (<3 mmol/l). Safety was assessed by side effect rate registration. Patients were randomized in 2 groups (G1 and G2): G1 patients (n=15) received Zocor 20 mg/day during 6 weeks, G2 patients (n=15) – Simvahexal 20 mg/day. After 6 weeks of therapy G1 patients were switched from Zocor to Simvahexal, G2 patients did not change their therapy. Simvahexal dose was increased to 30 mg/day, if the target level of LDL cholesterol had not been reached after first 6 weeks of therapy.

Results. After switching therapy from Zocor to Simvahexal 11 patients increased the dose to 30 mg/day, 3 patients kept the dose of 20 mg/day, 1 patient drop out. At the beginning of the study 15 patients received Simvahexal 20 mg/day, after 6 weeks the dose was increased to 30 mg/day in 8 patients, 7 patients kept the dose of 20 mg/day. After 6 weeks of therapy with Zocor 20 mg/day levels of the total cholesterol (TC) and LDL cholesterol reduced on 25,2% and 33,6% (p<0,001), respectively. Next 6 weeks of therapy with Simvahexal in the average dose of 27,7 mg/day this reduction reached to 30,9% and 39,9% (p<0,001), respectively. After 6 weeks of therapy with Simvahexal 20mg/day levels of the TC and LDL cholesterol reduced on 28,2%and 38%(p<0,001), respectively. Next 6weeks of therapywith Simvahexal in the average dose of 25,3mg/day this reduction reached to 29,6%and 42,5%(p<0,001), respectively. In G1 patients Zocor 20mg/day reduced atherogenesis index (AI) from5,2 to 3,3 (p<0,001) after 6weeks of therapy. Next 6weeks of therapywith Simvahexal in the average dose of 27,7mg/day this reduction reached to 3,1. In G2 patients AIwas reduced from4,1 to 2,4 (p<0,001) after first 6 weeks of therapy with Simvahexal 20 mg/day and remained at the same level during next 6 weeks of therapy. Both drugs were comparable in rate (6 cases for each) and intensity of side effects. Slight increase (in the normal range) of creatine kinaze, alanine aminotransferase and aspartate aminotransferase levels was observed during both therapies, but a little bit more prominent in Simvahexal one.

Conclusion. Simvahexal, is comparable with Zocor in terms of hypolipidaemic effect in 6-week therapy.We consider Simvahexal® as a generic therapeutically equivalent to original simvastatin drug.

28-33 521

Aim. To study effects of ramipril, molsidomine and their combinations on morphofunctional heart indices and clinical status of patients with chronic heart failure (CHF), which complicated an ischemic heart disease (IHD).

Material and methods. 41 patients with CHF class II-III (NYHA), which complicated IHD (postinfarction cardiosclerosis) were included in the study. Patients did not receive ACE inhibitors. Patients were split in 3 groups: patients of the 1st group received ramipril, patients of the 2nd group - molsidomine and patients of the 3rd group – combination of ramipril and molsidomine. Clinical examination, laboratory tests, electrocardiogram, cardiac ultrasonograthy, exercise tolerance test was performed before treatment and after 3 months and 1 year of treatment.

Results. Improvement of clinical status and decrease of class NYHA was found in 38,5% of patients in ramipril group; in 33,3% of patients in molsidomine group and in 23,1 % of patients in combined therapy group. Increase of ejection fraction on 17 % from initial level was found in patients receiving combined therapy; on 25,2% - in patients receiving molsidomine; and on 12,4% - in patients receiving ramipril. Decrease of residual volumes of a left ventricle also was detected.

Conclusion. All therapies (ramipril, molsidomine and their combination) in patients with CHF class II-III and postinfarction cardiosclerosis are clinically and hemodynamically effective in long term implementation.

34-38 415
Therapy of arterial hypertension in patients with overweight and obesity has peculiarities. Reasons for comparable study of efficacy and safety of therapies based on β-blockers (carvedilol and metoprolol) in this type of patients are presented. Study aims and design, efficacy and safety criteria are described.
39-45 672

Aim. To study effect of antihypertensive therapy with amlodipine maleat (Stamlo® M, “Dr. Reddy’s”, India) on morphofunctional heart indices, intensity of systemic inflammation and oxidative stress in patients with arterial hypertension (HT) with chronic obstructive pulmonary disease (COPD).

Material and methods. 20 patients with COPD II-III stage (GOLD 2006) in remission and HT 1-2 stage were involved in the study. Morphofunctional heart indices, respiratory function, levels of C-reactive protein (CRP) and oxidative stress (lipid peroxidation products (LPP) – acilhydroperoxides) were evaluated.

Results. Amlodipine maleat therapy provides target level of blood pressure (BP) according to ambulatory BP monitoring with improvement of pathological type of daily BP profile. Reduction of diastolic dysfunction of left and right ventricles was revealed. Therapy was safe in terms of respiratory function. Significant CRP and LPP levels reduction was observed.

Conclusion. Amlodipine maleat therapy has high antihypertensive effect, organoprotective properties and safety in hypertensive patients with COPD. Besides this therapy demonstrates systemic anti-inflammatory action and reduces oxidative stress.

46-52 1094

Aim. To compare two initial doses (50 or 100mg/day) ofmetoprolol succinate in control released presentation (Betaloc ZOK, AstraZeneca) for achievement of target level of heart rate (HR) in patients with stable course of ischemic heart disease (IHD).

Material and methods. 50 patients (34 men and 16 women, aged 61,3 y.o., in average) with IHD were involved into the open randomized comparative study. IHD duration was from 1 to 22 years (8,3 years in average). 47 patients completed study, 3 patients drop out because of side effects. Previous therapy with β-blockers or other HR reducing drugs was replaced on metoprolol. Patients were randomized in 2 groups (G1 and G2). The initial metoprolol dose was 50 mg in G1 patients and 100 mg - in G2 patients. The dose was enlarged twice if necessary. Study duration was 6 weeks. The change of HR, blood pressure, electrocardiogram parameters was evaluated. Patients filled in Seattle angina questionnaire initially and after 6 weeks treatment. Therapy tolerability was also estimated.

Results. In 6 weeks of therapy 61% of G1 patients and 87,5% of G2 patients (p<0,01) reached HR target. Dependence of achievement of target HR and dose of metoprolol was observed (r=0,3; p=0,056). Improvement of the HR control was accompanied by reduction of frequency of angina attacks and increase of life quality.

Conclusion. Metoprolol (Betaloc ZOK) 200 mg/day provides more effective HR control in patients with IHD vs metoprolol 50-100 mg/day and has good tolerability.

53-56 1240

Aim. To study effects of calcium channel blocker, amlodipine on indices of ambulatory blood pressure monitoring (ABPM), heart rate variability, corrected QT-interval and its dispersion, structural and functional heart indices, microcirculation in patients with arterial hypertension (HT).

Material and methods. 48 patients with HT of 1-2 stages were involved in the study. After 2 week wash-out period amlodipine (5-10 mg/day) therapy was started. ABPM, 24 hour electrocardiogram monitoring, echocardiography, laser Doppler flowmetry was performed initially and in 24 weeks of therapy.

Results. Amlodipine therapy increased microcirculation efficacy, reduced repolarization nonhomogeneity, contributed to myocardial electrophysiological stability. Besides it improved structural and functional heart indices, decreased systolic and diastolic blood pressure (BP), reduced indices of BP load during a day.

Conclusion. Amlodipine is effective antihypertensive medicine, having prominent cardio- and vasoprotective effects and good tolerability.

57-62 464

Aim. To study the effect of the monotherapy with calcium channel blockers (amlodipine, 5 mg/d and nifedipine retard, 40 mg/d) on heart rate variability (HRV) in elderly hypertensive patients with different rate of biological ageing.

Material and methods. 55 male hypertensive patients of 60-86 years with ischemic heart disease and chronic heart failure, class I-III (NYHA), were examined. Biological age was determined by the linear regression. HRV was determined by cardiointervalography and variation pulsemetry at the rest and in orthostatic test. Patients were split in to 2 groups (I - normal; II - fast ageing rate) and treated with the investigated drugs for 4 weeks. At the baseline and at the end of the study HRV and clinical blood pressure (BP) were determined.

Results. Normal sympathetic activity and moderate overactivity was observed in patients of I group, and prominent sympathetic overactivity - in patients of II group. Monotherapy with amlodipine in patients of I and II groups improved indices of HRV (variation range, dispersion and stress index) and provided target BP reduction. Monotherapy with nifedipine retard in patients of I group elevated variation range, decreased stress index and provided target BP reduction. Sympathetic activity was not changed in patients of the II group. Autonomic regulation was normalized due to amlodipine and nifedipine retard therapy in patients of the both groups.

Conclusion. The sympathetic overactivity is observed in elderly hypertensive patients. Monotherapy with calcium blockers improves HRV and provides target BP reduction.


63-66 610
Orotic acid is one of the intermediates in the pyrimidine biosynthesis. Mechanisms of physiological effects of orotic acid are poorly known. Analysis of data about these mechanisms is presented. Effects of orotic acid and magnesium orotate on cardiovascular system as well as therapeutic implementation of magnesium orotate in cardiology are discussed.
67-70 385
Dobutamine is inotropic drug indicated in systolic dysfunction. Data on dobutamine pharmacology, its effects on hemodynamics, coronary and peripheral blood flow, myocardial electrophysiology are presented. Clinical usage and the main contraindications of dobutamine are discussed.


71-76 388

Aim. To investigate the role of systemic inflammation and endothelial dysfunction as factors of cardiovascular risk in patients with ankylosing spondylitis.

Material andMethods. 100 patients with ankylosing spondylitis were included into the study. Screening for arterial hypertension (HT) and conventional cardiovascular risk factors (smoking, hyper- and dislipoproteinemia, body overweight, heredity and diabetes mellitus) was performed in all patients. 10-year coronary disease risk (Framingham scale) and 10-year risk of fatal cardiovascular event (SCORE scale) was calculated. Additionally the follows cardiovascular risk factors were assessed: C-reactive protein level (CRP), fibrinogen level, platelet count, antithrombin III activity, plasma fibrinolytic activity, vonWillebrand factor (vWF) activity, circulating endothelial cells (CEC) count. Besides, endothelial functionwas evaluated by Doppler-ultrasonography of brachial artery in testswith reactive (endothelium-dependent or flow-mediated dilation) and nitroglycerine (endotheliumindependent dilation) hyperemia. 30 healthy patients were included into control group and were comparable with patients of studied group on sex and age.

Results. 10-year coronary disease risk in patients with ankylosing spondylitis was significantly lower than this in patients of control group 4.0%(3,0; 7,5) vs 5.0%(3,0; 11,0), respectively (p<0,05). 10-year risk of fatal cardiovascular event in studied group was relatively low 1.0% (1.0; 2.0). However, analysis of the additional risk factors shown increased thrombogenic potential of blood, which was related to systemic inflammation activity: high platelets count, high fibrinogen activity, increased vWF activity, and decreased fibrinolytic activity. Moreover, signs of endothelial injury (increased level of CEC and vWF activity) and endothelial dysfunction were found in patients with ankylosing spondylitis.

Conclusion. Cardiovascular risk in patientswith ankylosing spondylitis estimated on the basis of conventional risk factors is not higher than this in general population. At the same time, these patients have signs of endothelial injure, dysfunction, and increased thrombogenic potential directly related to the systemic inflammation activity.We suppose these factors are responsible for the increased cardiovascular risk in patients with ankylosing spondylitis and, therefore, should be taken into account upon cardiovascular risk assessment.


77-84 1986

Clinical and clinicoeconomical studies review is presented as well as results of author’s comparative cost analysis on metoprolol tartrate (Betaloc) and metoprolol succinate (Betaloc ZOK) usage in patients with ischemic heart disease. Efficacy of metoprolol therapy is proven in randomized clinical studies in patients with angina and myocardial infarction (MI). In angina patients metoprolol prevents cardiac attacks, MI, reduces nitroglycerine consumption, increases exercise tolerability, prolongs the exercise time before ST segment depression (succinate better than tartrate), decrease of angina intensity. In MI patients metoprolol therapy reduces mortality, sudden death, recurring MI and the rate of early post MI angina attacks. Nowadays metoprolol is the only β-blocker having indication on secondary MI prevention. Besides for the present metoprolol succinate is the only β-blocker with proven direct antisclerosis effect. According to Swedish clinicoeconomical study in patients after MI secondary prevention with metoprolol therapy saves the costs in comparison with placebo. American clinicoeconomical model of metoprolol and atenolol usage in all patients with MI could result in significant reduction in mortality and recurring MI rate, prolong the life and improve its quality, save financial resources. The cost of monthly treatment of angina patient with metoprolol tartrate (Betaloc) and metoprolol succinate (Betaloc ZOK) is 135 and 354 rubles, respectively. The price range of comparative β-blockers in ascending order is the following: atenolol (Atenolol Nicomed) → metoprolol tartrate (Betaloc) → metoprolol succinate (Betaloc ZOK) → bisoprolol (Concor) → nebivolol (Nebilet). In conclusion, metoprolol therapy is the one of mostly economically reasonable approach.

85-90 291
Mechanisms of renal disorders in cardiovascular diseases are presented. The main of these mechanisms is an endothelium dysfunction. It is related with some factors: arterial hypertension, insulin resistance syndrome, diabetes type 2, dyslipidemia, obesity. Approaches to prevention of kidney disorder and cardiovascular complications are discussed with focus on usage of angiotensin II receptor blockers.


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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)