Rational Pharmacotherapy in Cardiology

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Vol 2, No 4 (2006)
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4-11 354

Aim. To study dynamics of the indices of heart rate variability (HRV) and heart remodeling in response on combined therapy with fosinopril and simvastatin in postmenopausal metabolic syndrome (MS). Material and methods. 95 women were dynamically examined (before and after 12 months of therapy with fosinopril and simvastatin) to assess heart rhythm variability (time and spectral domains) and remodeling with Holter ECG monitoring and echocardiography. Results. Fosinopril has resulted in blood pressure decrease, reduction in heart remodeling andmyocardial heterogeneity , which accompanied HRV rise with increase in parasympathetic activity. Simvastatin potentiated fosinopril positive effects on left ventricular hypertrophy , myocardial electric heterogeneity and autonomic modulation due to its prominent hypolipidemic and pleiotropic effect. Conclusion. In patients with postmenopausal MS medicines, which modified different elements of MS (ACE inhibitor and statin), not only have antihypertensive and hypolipidemic action, but also reduce the heart remodeling and improve the autonomic nervous system balance.

12-17 309

Aim. To estimate an effect of enalapril, angiotensin converting enzyme (ACE) inhibitor , on left ventricular hypertrophy and endothelium function in patients with arterial hypertension (HT). Material and methods. 41 patients with HT of I-III grade were included into the study. A part of patients received enalapril in an average daily doze of 10 mg. Parameters of microcirculatory reactivity and computer electrocardiogram analysis according to original technique were studied. Results. Microcirculatory indices showed that 6 month enalapril treatment resulted in significant improvement of disturbed function of vascular endothelium. Reduction of left ventricular hypertrophy also was demonstrated. Conclusion. ACE inhibitors should be widely recommended in hypertensive patients due to their vascular and heart remodeling positive effects.

18-24 328

Aim. To assess antihypertensive efficacy of monotherapy with indapamide (Akripamide, Akrihin, Russia) and its influence on blood levels of carbohydrates, lipids and electrolytes in patients with essential hypertension (EH). Methods. 30 patients with EH I-II degrees were treated with indapamide 2,5 mg daily during 3 months. Ambulatory blood pressure (BP) monitoring was made before and after the treatment as well as blood levels of carbohydrates, lipids and electrolytes were assessed. Results. 3-month indapamide monotherapy resulted in achievement of BP target levels in 76.6% of patients. Significant decrease in daily , day-time and nighttime BP , BP burden and daytime BP variability were observed. Number of patients with insufficient night decrease of systolic and diastolic BP was significantly decreased. No negative influence of indapamide on blood levels of lipids and electrolytes was observed. Conclusion. Indapamide is effective antihypertensive drug with satisfactory tolerance.

25-29 234

Aim. In multicentral program PRIORITY to estimate the efficacy of antianginal therapy after switching patients with stable angina from therapy with short-acting nitrates or isosorbide dinitrate in long-term acting formulation to therapy with isosorbide-5-mononitrate (Pectrol, KRKA, Slovenia) in once daily administrated presentation. Materials and methods. PRIORITY program was held in out-patient clinics of 14 cities. 286 patients with stable angina, who took short-acting nitrates or isosorbide dinitrate in long-term acting formulation, were included in research. Patients were switched without any break to the therapy with isosorbide-5-mononitrate (ISMN) in doze of 40 mg once a day , concomitant therapy was not changed. Initially and after 3 months of treatment with ISMN angina functional class, current therapy with nitrates and concomitant therapy were defined. Quality of life was also determined by questionnaire. Results. 275 patients finished programand 261 of themwere completely corresponded to the study protocol. The treatment with ISMN reduced the frequency and duration of angina attacks (p<0,001), the frequency of sublingual nitroglycerine intake, resulted in the reduction of functional class of angina (p<0, 0001), the increase in walk distance without chest pain or dyspnoea (p<0, 0001). According to questioning 3 months treatment with ISMN resulted in physical exercise tolerance increase (p<0, 0001), reduction in number of side-effects of nitrates therapy (p<0, 0001) and frequency of angina attacks (p<0, 0001). Intensity of psychological discomfort was reduced (p<0,0001) and satisfaction with therapy was increased (p<0, 0001). Conclusion. Switching from short-acting nitrates or isosorbide dinitrate in long-term acting formulation to the therapy with ISMN showed corrective influence on life quality in patients with stable angina: frequency and duration of angina attacks significantly reduced, physical exercise tolerance increased, psycho-emotional condition and patient compliance improved.

30-35 287

Aim. To study endothelium vasomotor function (EF) in patients with ischemic heart disease (IHD) and the influence of angiotensin converting enzyme inhibitor enalapril (Enam, Dr .Reddy’s, India) on it. Material and methods. 87 patients were examined totally. 49 patients were suffering from IHD: 18 patients were younger than 60 years old and 31 patients were older . The combination of arterial hypertension (HT) and IHD were registered in 38 patients: 18 patients were below and 20 patients were above 60 years old. All patients additionally to basic IHD therapy took enalapril in dose 2,5-30 mg/daily during 12 weeks. Before the beginning and in the end of treatment cuff test, test with nitroglycerine, bicycle exercise test and Holter monitoring were made, the thickness of intima-media complex of carotid artery and the level of endothelin-1 in blood plasma were defined. Results. EF disorders were shown in IHD, maximal disorders were determined in patients with combination of IHD and HT. EF disorders were also more expressive in patients of elder group. Enalapril restored of cuff tests results, nitroglycerine tests results, reduced a number of myocardial ischemia episodes and provided target blood pressure in 60, 5% patients with HT. Conclusion. Enalapril improves endothelium vasomotor function, endothelium reaction on nitroglycerine and clinical course of IHD and HT.

36-40 295

Aim. To study daily changes of central hemodynamics (CHD) in patients with chronic heart failure (CHF) and the effects of therapy. Materials and methods. 22 patients with ischemic heart disease and CHF of III-IV functional class (FC) by NYHA, age 60,5±10,5 were observed. Patients were suffering from night-time dyspnoea attacks and had pulmonary artery occlusion pressure (PAOP) 15-20 mm Hg. CHD was monitored invasively before the treatment and after 4 weeks of CHF treatment. Results. According to the cardiac index (CI) at admission patients were split into two groups. 9 patients of group-I had CI ≤2,15 l\min\m2, and 13 patients of group-II had CI >2,15 l\min\m2. In patients of group-I CI increased in 4 weeks of treatment. The treatment caused considerable clinical improvement in all patients. The CHD indexes also improved. Initially evening-night-time peaks of PAOP (р≤0,002), systolic (SBP) (р≤0,003), diastolic (DBP) (р=0,002) and average (BPa) (р=0,0007) blood pressure (BP) as well as double multiplication (DM) (р≤0,008) were registered in patients of group-I. At the end of treatment only evening-night increase in DBP (р=0,002) and BPa (р≤0,006) were noted. In patients of group-II after 4 weeks of treatment CI decreased or didn’t change. Towards 28-th day of treatment 10 patients had clinical improvements. Only one patient’s FC NYHA increased. At the end of treatment the normalization of CHD was registered totally in group. Initially evening-night-time peaks of PAOP (р≤0,002), SBP (р≤0, 0001), CI (р=0,057) and DM (р=0,084) were registered in patients of group-II. At the end of treatment evening-night-time peaks of PAOP (р≤0,015), SBP (р≤0,044), CI (р≤0,005) and DM (р≤0,044) still remained. Besides, evening-night-time peaks of cardiac output (р≤0,01) and systolic index (р≤0, 06) have added. Conclusion. In patients with CHF with initial CI ≤2,15 l\min\m2 treatment results in the normalization of CHD and its daily rhythm. In patients with CHF with initial CI >2,15 l\min\m2 the treatment leads to the normalization of CHD, though it doesn’t correct daily rhythm disturbances of circulation.


41-46 192

Drug quality in modern market is discussed. There is an increase of a number of drugs that don’t meet to the quality requirements.Most of them are produced by Russian manufacturers, which number has also increased recently. According to official data 6-10%of all medicines are counterfeit. Quality reduction is also connected with a huge number (80%) of reproduced drugs (generics). Considerable part among generics doesn’t pass required evaluation of equivalence with original product. Approved deviations (according to Russian regulative rules) in pharmacological equivalence may reach 5%, and in pharmacokinetic equivalence -25%. Evidences of pharmacodynamic (therapeutic) equivalence are not required at all. At the same time, author advocates the production of qualitative generics that can providemodern and accessible treatment. Generic quality should be confirmed by randomized studies with cross-over designed comparison with original drug in parallel groups. The examples of the generics with such evidences are demonstrated. The requirements to the data about drugs are given to help the physician to make a right independent estimation of its quality.

47-52 345

Results of HOPE trial are analyzed. It is noted, that treatment with angiotensine converting enzyme inhibitor (iACE) ramipril improves the prognosis in high risk cardio-vascular patients. The objectives and study design of ONTARGET/TRANSCEND trials are introduced. Perspectives of joint use of ACE inhibitor and antagonist of angiotensin II receptor are discussed.

53-57 297

According to WHO data, arterial hypertension (HT) is revealed in 15-20% of pregnant women. In different regions of Russia the incidence of pregnancy HT varies from 7 to 29%. In women with HT started before pregnancy , perinatal losses are observed in 3, 8%, premature births – in 15, 3% and intrauterine growth retardation - in 16, 6%. Physiological gestational changes of hemodynamics are described. Hypertensive pregnant patients of high and low risk are defined. Non-pharmacological treatment of pregnant women with HT is presented in details. Antihypertensive therapy may not be used in hypertensive patients of low risk with blood pressure (BP) of 140-160\90-110 mm Hg. If BP is higher antihypertensive therapy should be used immediately. Dihydropyridine calcium antagonists (CA) is drugs of choice for HT treatment during pregnancy , especially “advanced” CA of the third generation. They have predictable efficacy. It is possible to use short-acting nifedipine for treatment of acute HT in pregnant patients.


58-62 303

It is reported that the implementation in clinical practice thrombolytic (fibrinolytic) therapy resulted inmortality reduction during firstmonth after myocardial infarction from 17-18% to 5-8%. Different details of this therapy are considered: terms of thrombolysis since the beginning of myocardial infarction, alternative methods of coronary blood flow recovery , indications and contraindications, complications and side effects, estimation of thrombolysis efficacy. Fibrin-selective and fibrin-non-selective drugs are presented. Different fibrinolytics are described: streptokinase, anistreplase, alteplase, reteplase, tenekteplase. The results of large randomized clinical trials devoted to fibrinolytic therapy of myocardial infarction are analyzed: GISSI, ISSIS, TIMI, GUSTO, INJECT, ASSENT. The possibility to increase in efficacy and safety of fibrinolytics by their combination with acetylsalicylic acid, IIb/IIIa receptor inhibitors and heparins are discussed.

63-70 291

Neurohumoral model of pathogenesis of chronic heart failure (CHF) made it possible to develop new therapeutic approaches in patients with CHF . However , it became obvious that the ways of activation of neurohumoral systems in CHF are much more complicated. The increase in local synthesis of hormones causes the activation of inflammatory cytokines and protooncogenes, which have various negative effects. This allowed formulating immunoinflammatory conception of CHF pathogenesis, according to which the increase in interleukine-6 blood level is the marker of unfavorable prognosis for CHF , and the level of tumor necrosis factor-α (TNF-α) straightly correlates with severity of clinical condition and neurohumoral activity in CHF . The growth of TNF-α in CHF progressing as well as its reduction in successful treatment do not exclude the probability of positive effect of therapy , focused on the reduction of TNF-α concentration. The pathogenesis peculiarities of CHF including cytokine aggression demand the necessity of development of new therapy approaches with the use of cytokine system modulators.


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