Rational Pharmacotherapy in Cardiology

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Vol 4, No 2 (2008)



6-12 537

Aim. To study effects of pentoxifylline in combination with basic therapy on functional status, intracardiac hemodynamics, neurohormones and proinflammatory cytokines levels in patients with chronic heart failure (CHF) complicated ischemic heart disease (IHD).

Material and methods. 55 patients with CHF complicated IHD (83,6% men and 16,4% women) were involved in the study. Duration CHF was 2,4 years in average. Class I of CHF (NYHA) was registered in 5 patients (9,1 %), class II - in 33 patients (60,0 %), class III - in 16 patients (29,1 %), class IV in 1 patient (1,8 %). Dynamics of life quality, severity of clinical status, functional reserve, intracardiac hemodynamics, neurohormones and proinflammatory cytokines levels was assessed during 9 months of therapy.

Results. Pentoxifylline, added to standard therapy of CHF, resulted in improvement of life quality, intracardiac hemodynamics and clinical status of the patients with CHF of I-II class (NYHA). Besides reduction in proinflammatory cytokine (tumor necrosis factor-α, interleukin-6) and neuronhormone levels was found in patients with CHF of I-II class.

Conclusion. Pentoxifylline can be useful in combined therapy of CHF

13-18 440

Aim. To study inheritance patterns of atrial fibrillation (AF) and association of primary and secondary AF with gene polymorphism of β1-adrenoreceptors.

Material and methods. 103 probands with AF and their 301 relatives of I, II, III degrees (basic group) and 82 probands without heart diseases and their 163 relatives of I and II degrees (control group) were examined. Examination included evaluation of electrophysiological indicators of sinoatrial node, electrocardiogram monitoring, veloergometry, echocardiography as well as assessment of gene polymorphism of β1-adrenoretseptors.

Results. Accumulation of AF in probands families was founded. Segregation analysis of idiopathic AF revealed autosomal-dominant type of its inheritance.

Сonclusion. The heterozygote genotype of gene β1-adrenoretseptors Ser49Gly is one of genetic predictors of primary and secondary AF.

19-22 1245

Aim. To study efficacy and tolerability of isosorbide-5-mononitrate (IMN) in various presentations in comparison with isosorbide dinitrate (IDN) in usual tablets in patients with stable angina.

Material and Methods. 22 patients (5 women and 17 men) with stable angina of II-III functional class were involved into open randomized comparative crossover study. Patients were split in 3 groups and received each of studied drugs during 4 weeks. IDN (Nitrosorbide, Nizpharm, Russia) in usual tablets 10 mg prescribed for 3 times a day administration; IMN (Monocinque,Berlin-Chemie, German) in tablets 20 mg prescribed for 2 times a day administration. After 1 week therapy the doses of IDN or IMN doubled if it was clinically necessary. Retarded presentation of IMN (Monocinque Retard, Berlin-Chemie, German) in capsules 50 mg prescribed once daily. Drug efficacy was evaluated by changes in clinical symptoms, number of angina attacks, demand in short-acting sublingual nitroglycerin as well as physical activity tolerance.

Results. After 4 weeks 18 patients completed study, 2 patients dropped out because of protocol nonobservance and 2 patients dropped out because of side effects (headache). IDN therapy in adjusted dose provided antianginal effect in 15 (83,3%) patients: a number of angina attacks decreased in 39,6%, short-acting nitroglycerin demand reduced in 47,7%. Monocinque in adjusted dose provided antianginal effect in 16 (88,9%) patients: a number of angina attacks decreased in 60%, short-acting nitroglycerin demand reduced in 63%. Monocinque Retard provided good antianginal effect in 18 (100%) patients: a number of angina attacks decreased in 72%, short-acting nitroglycerin demand reduced in 84,8%. There were not significant differences in frequency and severity of headache between studied drugs.

Conclusion. IMN therapy with both presentations (administrated 1 or 2 times a day) was more convenient and effective than IDN (administrated 3 times a day).

23-29 556

Aim. To evaluate the incidence of acetylsalicylic acid (ASA) and clopidogrel resistance in patients with acute coronary syndrome with ST-segment elevation and to find out possible clinical factors, contributing to this state.

Material and methods. 58 patients with acute coronary syndrome with ST-segment elevation (49 men, 9 women) were included into the study. Age of patients ranged from 37 tо 84 y.o. (60,8±12,3 y.o. in average). Platelet aggregation was assessed by the Born’s method. Level of arachidonic acidinduced aggregation ≥20% considered as ASA resistance. Decreasing of ADP-induced platelet aggregation ≥20% considered as ASA resistance. Decreasing of ADP-induced platelet aggregation <10%, 10-29%, and ≥30% compared to the basal level considered as clopidogrel resistance, “partial clopidogrel resistance” or clopidogrel sensitiveness, respectively.

Results. ASA and clopidogrel decreased arachidonic acid-induced and ADP-induced aggregation after 7 days of the therapy compared to the basal levels (р<0,05). The highest incidence of resistance was registered in patients with diabetes mellitus (71,1% to ASA, 57,1% to clopidogrel) and obe-sity (42,9% to clopidogrel).

Conclusion. The incidence of ASA and clopidogrel resistance reached to 28,9% and 24,4% respectively in patients with acute coronary syndrome with ST-segment elevation. The prevalence of antiplatelet therapy resistance is significantly higher in patients with diabetes mellitus and obesity (р<0,05). The incidence of early complications of acute myocardial infarction is higher in patients resistant to ASA and clopidogrel.

30-33 1726

Aim. To compare efficacy of carvedilol and bisoprolol in patients with chronic heart failure (CHF) and diabetes mellitus (DM) type 2 after myocardial infarction (MI).

Material and methods. 60 patients (45-70 y.o.) with CHF 2-3 functional class according to NYHA and DM type 2 after MI (3-4 week) are included in the study. Patients are randomized on 2 groups. All patients received basic therapy of CHF. Besides patients of 1st group (n=30) were treated with carvedilol (Talliton, Egis) 29,0±2,5 mg daily. Patients of 2nd group (n=30) were treated with bisoprolol (6,0±0,5 mg/day). Both groups were similar on age, sex, disease severity, haemodynamic parameters and basic therapy doses. Life quality, functional reserve, echocardiography, kidney function, heart rate variability (HRV), lipid and glucose metabolism were estimated initially and in 16 weeks of treatment.

Results. Carvedilol and bisoprolol therapy of patients with CHF and DM after MI resulted in improvement of clinical status, kidney function and increase in HRV. Carvedilol had clinical advantages in comparison with bisoprolol in effects on myocardial remodeling, kidney function and HRV. Carvedilol favorable effects on lipid and glucose metabolism were observed.

Conclusion. Carvedilol has a number of significant advantages in comparison with bisoprolol in the therapy of patients with CHF and DM after MI.

34-37 580

Aim. To evaluate efficacy and safety of a new drug of amlodipine – S-amlodipine (Azomex, Emcur, India) compared to original drug of racemic amlodipine (Norvasc, Pfizer, USA) in patients with arterial hypertension (HT) of I-II grade.

Material and methods. 39 patients with HT of I-II grade were randomized into two groups and took drugs of amlodipine during 8 weeks. Ambulatory blood pressure monitoring (ABPM) was undertaken before treatment and at the end of treatment.

Results. 34 patients completed 8-week therapy. Both drugs showed antihypertensive effect: significant decrease in average levels of systolic and diastolic blood pressure (BP) recorded by office and ABPM measurements. Compared to racemic amlodipine S-amlodipine caused bigger decrease in systolic and diastolic BP and bigger decrease in daily and 24-hour average diastolic BP after 4 week of therapy.

Conclusion. S-amlodipine is effective antihypertensive drug, showing more significant BP decrease in comparison with this of racemic amlodipine after 4 weeks of treatment.

38-40 662

Aim. To study effect of mildronate on stream-dependent vasodilation in patients with chronic heart failure (CHF).

Material and methods. 30 patients with CHF taking standard therapy (diuretic, ACE inhibitor, β- blocker) as well as 30 healthy volunteers have been examined. Test of reactive hyperemia (RH) of brachial artery (BA) was performed in all patients. RH test was performed in patients with CHF in double blind crossover manner before and after infusion of NaCl-isotonic solution (placebo) or mildronate 1000 mg in NaCl-isotonic solution.

Results. Increase in BA diameter (%∆D) in patients with CHF was less than this in control group (p<0,01) during RH test. After mildronate infusion increase in %∆D during RH phase was observed (from 8,6+0,8 to 14,4+0,9%, р><0,001). After placebo infusion BA diameter did not change significantly (from 9,3+0,7 to 10,4+0,8%, p>0,05).

Conclusion. Mildronate improves endothelium-dependent vasodilation in patients with stable CHF.

41-46 639

Aim. To study ramipril effect on parameters of ambulatory blood pressure (BP) monitoring, cardio-vascular remodeling parameters in patients with arterial hypertension (HT) and ischemic heart disease (IHD).

Material and methods. 40 patients with HT (stage 1-2) combined with IHD (functional class 1-2) were included in the study. All patients were randomized in 2 groups. Patients of the 1st group received basic therapy with aspirin, statin and ß-blocker. Patients of the 2nd group received the same therapy as well as ACE inhibitor ramipril (Hartil, EGIS). Changes in clinical status, daily BP profile, cardio-vascular remodeling parameters were evaluated.

Results. After 12 week treatment clinical improvement was revealed in the both groups of the patients. Ramipril contributed additional pulse BP and BP loading reduction, regression of left ventricular hypertrophy, improvement of systolic and diastolic left ventricle function, increase in brachial artery diameter.

Conclusion. Ramipril inclusion in the basic therapy of patients with HT and IHD increases in efficacy of antihypertensive treatment and improves structural and functional conditions of heart and vessels.

47-50 477

Aim. To study effects of genes SLCO1B1 and MDR1 polymorphism on atorvastatin pharmacokinetics and pharmacodynamics in patients with primary hypercholesterolemia.

Material and methods. 21 patients (9 men and 14 women; 57 y.o. in average, all were Caucasians) with primary hypercholesterolemia (NCEP criteria) were involved in the study. All patients had total cholesterol plasma level >5.9 mmol/l after 4-week course of lipid-lowering diet. Atorvastatin (80 mg once daily in the first treatment day) was given to patients for pharmacokinetics estimation. Blood samples for analysis were taken before and after drug administration. Genes SLCO1B1 and MDR1 polymorphism screening was made by polymerase chain reaction.

Results. Treatment efficacy in patients with SLCO1B1.с521СС genotype was less than this in patients with other genotypes. Genes MDR1 polymorphism have no influence on treatment efficacy. There is no correlation between genotype and drug adverse effects rate.

Conclusion. Polymorphism of genes responsible for protein-transporters (first of all ОАТР-С) can significantly determine drug pharmacokinetic and individual response on atorvastatin therapy.


53-57 663

Classification of calcium antagonists (CA) is presented. Results of the large clinical trials (STONE, STOP-Hypertension-2, ALLHAT, ASCOT-BPLA etc.) devoted to estimation of CA effects on the risk of cardiovascular complications are analyzed. The significant place of dihydropyridine CA in current guidelines on arterial hypertension and ischemic heart disease therapy is underlined. Results of a pilot study on comparison of two amlodipines (original Norvasc and generic Stamlo M) are discussed.

58-65 582
Results of trials on the therapy of patients with acute myocardial infarction (MI) and glucose metabolism disturbances are discussed. According to author’s data, 67% of patients with MI have glucose tolerance disturbances including 44% of patient with these reaching the level of diabetes mellitus (DM). Mortality risk in patients with MI and DM is some times higher than this in patients with MI without glucose metabolism disturbances. Active glucose correction results in significant mortality risk reduction. It is necessary to reduce glucose blood level to normal one as soon as possible in patients with MI and DM. It can be managed with insulin, if the glucose blood level is intensively increased or with per oral glucose lowering medicines, if there is moderate hyperglycemia. In spite of wide usage of these class drugs, it is not still clear which medicine is mostly effective in patients with MI and glucose metabolism disturbances.
66-75 560

Problem of anticoagulant choice in patients with acute coronary syndrome (ACS) is discussed. Results of the main trials on low-molecular heparin therapy in patients with ACS as well as recommendations of European cardiology society and American heart association are presented. Peculiarities of other therapies (thrombin inhibitors, Ха-factor inhibitors) in ACS are surveyed.


76-80 861

Calcium antagonists (CA) therapy of patients with arterial hypertension is focused on the base of current recommendations. Results of some large clinical trials confirm high antihypertensive efficacy of this therapeutic class. Special attention is devoted to implementation of fixed combinations on the basis of CA. Advantages of these combinations in hypertension therapy are discussed.

81-84 601
Approaches evolution to studying of beta-blockers influence on platelet aggregation is reviewed. The current view on of beta-blocker antiplatelet effects is presented on the basis of physical and chemical drug properties (water repellency, dipole moment, molecular mass). Trail results on carvedilol influence on platelet aggregation are focused.
85-88 476

Aim. To study the effects of furostanol glycosides from cultured Dioscorea Deltoidea cells (DM-05, Institute of Plant Physiology, RAS) on physiological and biochemical markers of endothelial function in rats with hypoestrogen-induced endothelial dysfunction.

Material and methods. 10 female rats of Wistar line, with body mass 200-300 g have been included in the experiment. The bilateral ovariectomy was performed in rats to produce the model of hypoestrogen-induced endothelial dysfunction. Rats were treated with the injections of DM-05 during 6 weeks. False ovariectomy was performed in rats of control group (n=10).

Results. DM-05 restored the levels of stable metabolites of nitric oxide (NO) which reflex endothelial NO-synthase activity. Besides DM-05 corrected blood pressure and endothelial function. Experiments on open heart showed that DM-05 protects the cardiac tissue from hypoestrogen-induced hyperadrenoreactivity.

Conclusion. Treatment with plant origin substances with estrogen-like activity can be a perspective approach to the correction of endothelial function and decrease in cardiovascular risk in menopause women.

89-92 687

Aim. To study effects of ACE inhibitor perindopril on markers of endothelial dysfunction in therapy of patients with arterial hypertension (HT).

Material and methods. 82 patients with HT, complicated by ischemic stroke were involved in the study. 30 patients with uncomplicated HT were included into control group. Antihypertensive therapy with perindopril (52 patients) or amlodipine (30 patients) was conducted additionally to standard neurotropic therapy in hypertensive patients with ischemic stroke. Phase-contrast microscopy and enzyme immunoassay were used for screening of endothelial dysfunction markers (blebbing, desquamated endothelial cells, membrane-liberated parts, sPECAM-1).

Results. Reduction in levels of markers of endothelial dysfunction was observed among patients treated with perindopril in comparison with patients who did not receive ACE inhibitor or patients of control group. Target levels of blood pressure were reached in 96% of patients treated with perindopril. Сonclusion. ACE inhibitors in therapy patients with HT reduce endothelial dysfunction additionally to antihypertensive effect.


93-123 411
The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension and of the European Society of Cardiology.
126-132 638

Task Force of the European Society of Cardiology.

Djamaleddine Nibouche MD, Karlen Adamyan MD, Kurt Huber MD, Hugo Ector MD, Izet Masic MD, Rumiana Tarnovska MD, Mario Ivanusa MD, Vladimír Staněk MD, Jørgen Videbæk MD, Mohamed Hamed MD, Alexandras Laucevicius MD, Pirjo Mustonen MD, Jean-Yves Artigou MD, Mamanti Rogava MD, Michael Böhm MD, Eckart Fleck MD, Gerd Heusch MD, Rainer Klawki MD, Panos Vardas MD, Christodoulos Stefanadis MD, József Tenczer MD, Gianluigi Nicolosi MD, Aleksandras Laucevicius MD, Joseph Elias MD, Aleksandras Laucevicius MD, Abdelhamid Moustaghfir MD, Olaf Rødevand MD, Piotr Kułakowski MD, Victor A. Lusov MD, Rafael G. Oganov MD, Arsen Ristic MD, Gabriel Kamensky MD, Miran F. Kenda MD, Christer Höglund MD, Thomas F. Lüscher MD, René Lerch MD, Sami Kabbani MD, Habib Haouala MD, Vedat Sansoy MD, Alexandr Shumakov MD, Adam Timmis MD.

(Редакторы кардиологических журналов Европейских национальных обществ кардиологов; подробные данные см. в Приложении).

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