Rational Pharmacotherapy in Cardiology

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Vol 7, No 6 (2011)
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670-676 5713

Aim. To evaluate gender differences in effectiveness of antihypertensive therapy with losartan in comparison with enalapril therapy. Material and methods. Open-label controlled crossover study in parallel groups was conducted during 3 months. A total of 120 patients aged 20-45 years with arterial hypertension (HT) of 1 and 2 degree were split into 4 groups with 30 patients in each: 1A, 1B – men; 2A, 2B – women. For the first 6 weeks patients of the 1A, 2A groups received enalapril 5-20 mg while patients of 1B, 2B – received losartan 50-100 mg. Then the therapy was crosswise changed. Results. Initial blood pressure (BP) levels did not differ significantly in men and women. In women start therapy with losartan decreased systolic BP (BPs) more effectively than enalapril therapy did (18.2±5.4% vs 15.2±4.3%, р=0.02). In men enalapril and losartan start therapies did not show significant differences in BP reduction (13.8±4.5% vs 14.6±4.6%, р=0.539). Follicule-stimulating hormone (FSH) level in women correlated positively with age (r=0.826; p=0.0001), HT duration (r=0.498; p=0.0001), BPs level (r=0.466; p=0.001), microalbuminuria level (r=0.583; p=0.0001) and negatively – with glomerular filtration rate (r=-0.58; p=0.0001). Conclusion. Losartan is more effective than enalapril as a start therapy in 20-45-year-old women. In women FSH level correlates with age, HT duration, BPs and microalbuminuria levels, glomerular filtration rate.

677-684 1140

Aim. To analyze the literary and own data about clopidogrel influence on platelets during inflammation and to reveal particularities of its usage in ischemic heart disease (IHD) patients with active inflammation. Material and methods. The platelet morphology and a number of leukocyte-platelet aggregates (LTA) were investigated with scanning electron microscopy in 110 patients with stable angina pectoris of I-III functional class and 18 healthy volunteers. Spontaneous and ADP-induced platelet aggregation were assessed with laser aggregatometre manufactured by LLC “BIOLA”. Mean platelet volume (MPV) was estimated with the hematological analyzer . All investigations were performed in IHD patients before and after 2 months of clopidogrel treatment 75 mg a day. Results. IHD patients demonstrated appearance of LTA and big reticular platelets in the blood, increase in MPV and spontaneous aggregation. ADP-induced platelet aggregation was rarely increased probably due to acetylsalicylic acid therapy in all IHD patients. These platelet activity changes are connected with increased risk of thrombotic events and correlated with inflammation markers levels. After 2 months of clopidogrel treatment LTA number reduced in 4 times and big reticular platelets number decreased in 2.5 times as well as MPV and spontaneous aggregation achieved the normal ranges. Conclusion. Clopidogrel has not only antithrombotic effect but also can diminish platelets morphological and functional changes connected with inflammation.

685-689 682

Aim. To evaluate an antihypertensive efficacy and influence on the arterial stiffness of 24-week treatment with metoprolol tartrate in patients with hypertension (HT) degree 1-2. Material and Methods. Patients with HT degree 1-2 (n=38) received therapy with metoprolol tartrate 50-200 mg QD for 24 weeks. Bifunctional daily blood pressure (BP) and electrocardiogramm monitoring with evaluation of central aortic pressure indicators as well as volume sphygmography were performed at baseline and after 24 weeks of therapy. Results. The 24-week  therapy with metoprolol  tartrate was effective  in 47.2% of patients. Significant  improvement  in central aortic pressure  [systolic BP decreased  from 129.8±7.3  to 118.8±7.2 mm Hg; p<0.001; dyastolic BP decreased from 90 (87;93) to 80 (77;84) mm Hg; p<0.001] with the not significant changes of augmentation index (from 18.3±13.2 to 19.5±13.4; p>0.05). Significant reduction in arterial stiffness indexes was revealed with volume sphygmography: CAVI1 from 8.6 (8.1;9.6) to 8.0 (7.3;8.3); p<0.01; L-CAVI1 from 8.9 (7.6;9.9) to 7.9 (7.2;8.5), p<0.001. Conclusion. Metoprolol tartrate is an effective antihypertensive drug that improves the structural and functional properties of arteries.

690-697 19856

Background. The clinical significance of idiopathic mitral annular calcification (MAC) often diagnosed by echocardiography in elderly patients currently is not sufficiently studied. Aim. To study the clinical and echocardiographic characteristics of the cardiovascular system in patients with MAC aged 65 and older without diabetes mellitus and renal failure. Material and methods. Study included 100 patients with MAC, consecutively identified by 2D transthoracic echocardiography performed with relation to cardiovascular disease symptoms in 910 outpatients aged 65 years or older; the comparison group included 65 of consecutively studied patients without MAC. Results. Patients with MAC were older than patients without MAC (72.4±5.4 years vs 70.2±4.3 years; p<0.05) and had higher frequency of moderate or severe hypertension (99.0% vs 90.8%, p<0.05), myocardial infarction (adjusted incidence rate [AIR] 1.72; 95% confidence interval [CI] 1.12-2.55; р<0.05) and heart conduction disorders (AIR 3.25; 95%CI 2.45 to 4.30; р<0.05). At the same time the age-adjusted frequency of ischemic heart disease (AIR 1.12; 95%CI 0.9-1.39; р>0.05) and atrial fibrillation (AIR 0.94; 95%CI 0.52-1.56; р>0.05) was not significantly different in patients with and without MAC. Multivariate analysis adjusted for age and total cholesterol level obtained significant associations of MAC presence with symptomatic atherosclerotic peripheral arterial disease (p <0.001; ß=0.410). The frequency of stroke in patients with and without MAC did not differ (p>0.05). In the group of patients with MAC as compared to patients without MAC echocardiographic evaluation showed higher incidence of mitral regurgitation (AIR 1.51; 95%CI 1.21-1.82; p<0.05), left atrium increased size (AIR 1.68; 95%CI 1.27-2.23; p<0.05), concentric left ventricular hypertrophy (AIR 2.15; 95%CI 1.67-2.75; p<0.05), mitral valve thickening (100.0% vs 30.7%, p <0.001), aortic valve calcification (49% vs 0%, p <0.001), aortic regurgitation 1-2 degree (67.0% vs 13.9%, p <0.001). Conclusion. The study revealed some echocardiographic and clinical features associated with the MAC in elderly patients.

698-702 648

Aim. To study efficacy and tolerability of original and generic simvastatin in patients with hyperlipidemia. Material and methods. Patients (6 men and 24 women) aged 38 to 77 years, which needed in lipid-lowering therapy were included into the open, crossover , randomized, comparative study of efficacy and tolerability of original and generic simvastatin. The drug effects on the blood levels of total cholesterol (TC), high density cholesterol (HDC), triglycerides (TG), low density cholesterol (LDC), and tolerability of treatment were evaluated. The treatment duration (with a change of medications) was 12 weeks. Results. The target levels of LDC after 8 weeks of treatment with both generic and original simvastatin (20 mg/day) were achieved in 10 (71.4%) patients in each group. After 8 weeks of therapy with generic and original simvastatin TC decreased from 6.4±0.8 to 4.4±0.6 mmol/l (p<0.001) and from 6.0±0.7 to 4.1±0.7 mmol/l (p<0.001), respectively. LDC levels decreased from 4.4±0.7 to 2.4±0.4 mmol/l (p<0.001) and from 4.2±0.7 to 2.2±0.6 mmol/l (p<0.001), respectively. Both simvastatin medications led to similar changes in blood lipid spectrum and had comparable tolerability. Conclusion. The lipid-lowering effect of the generic simvastatin is comparable to this of original simvastatin. That means generic medication is therapeutically equivalent to original one.

703-707 458

Aim. To compare efficacy of different fixed antihypertensive combinations in achievement of the target level of blood pressure (BP), to evaluate the dynamics of endothelium-dependent vasodilation (EDVD) and microalbuminuria (MAU) and to calculate cost-effectiveness ratio (CER). Material and methods. Patients (n=75) with moderate hypertension (HT) accompanied by type 2 diabetes (DM) were studied. The patients were randomized in groups A, B or C. Patients of group A (n=25) received a fixed combination of the original perindopril+indapamide, patients of group B (n=30) — a fixed combination of the generic enalapril+indapamide, patients of group C (n=20) — a fixed combination of the original enalapril+hydrochlorothiazide. Office BP was examined within the 4, 8 and 12 weeks, EDVD and MAU were determined initially and after 12 weeks of therapy. CER was also calculated. Results. The maximal antihypertensive effect was observed in group C (systolic BP (SBP) decreased in 46.6±1.3 mm Hg), followed by group A (SBP decreased in 43.1±0.8 mm Hg) and B (SBP decreased in 40.0±0.8 mm Hg). The groups were distributed as follows (in descending order): according to EDVD rise - group A (Δ4.52%), C (Δ3.14%) B (Δ3%); according to MAU prevalence rate reduction - group A (from 48% to 8%), B (from 40% to 23%) and C (from 40% to 25%). The “C” combination provided the lowest cost of BP reduction (12.33 rubles/mm Hg) and correction of MAU prevalence rate (1 514 rubles/case). According to EDVD improvement combination “A” had the lowest CER (2 805 rubles/case). Conclusion. According to pharmacoeconomic analysis the fixed combination of original enalapril+hydrochlorothiazide and the fixed combination of original perindopril+indapamide should be used in patients with moderate arterial hypertension, endothelial dysfunction and/or MAU.

708-712 450

Aim. To compare survival rate and quality of life in geriatric patients after coronary stenting or after basic pharmacotherapy only. Material and methods. 135 patients of geriatric age with ischemic heart disease (IHD) were included into the study. Coronary stenting with the subsequent basic pharmacotherapy was carried out in 70 patients, other 65 patients received basic pharmacotherapy only. Additional examinations (echocardiography , coronaroventriculography , treadmill test) were performed during the 12 months follow-up for indications other than standard clinical and laboratory examinations. Total mortality and  myocardial infarction rate, quality of life indices, and instrumental ex- aminations data were analyzed. Results. During one year after coronary stenting the overall mortality risk reduced in 3.3% and risk of non-fatal myocardial re-infarction decreased in 2.0%. Besides significant reduction in hospitalization rate, clinical improvement in stable angina course, increase in coronary heart reserve were observed in patients after PCI in comparison with these in patients received only standard pharmacotherapy. At the end of follow-up according to echocardiography data patients undergone coronary stenting shown increase in the left ventricle ejection faction (from 47.5±6.65% to 52.2±4.27%; р<0.010). This was not observed in patients with pharmacotherapy only (from 48.3±6.40% to 49.1±5.86%). Conclusion. Coronary stenting in geriatric IHD patients is an effective method of treatment. It increases quality of life due to reduction in the hospitalization rate and improves clinical course of stable angina.

713-717 490

Aim. To study dynamics of risk factors of ischemic heart disease (IHD) in patients trained in "School of Health" by general practitioners (GP) of rural medical office (RMO) and family outpatient clinic (FOC).  Material and methods. Patients (n=67, aged 56.1±0.9) with stable angina and IHD risk factors were examined. All patients were trained in 3 "Schools of Health" in the city of Tashkent and rural Surkhandarya region. Follow-up duration was 2 years (2008-2010). Results. During 2 years of follow-up significant reduction in influence of IHD risk factors was found in patient according to elaborated mathematic model: dyslipidemias in 40.3%, improper feeding in 25.3%, anxiety-depressive disorders in 14.6%, low physical activity in 7.4%, smoking in 6.6%. Conclusion. Organization of the "School of Health" by GP in RMO and FOC is rational and usage of training programs for struggle with IHD risk factors is effective.

718-724 675

Aim. To analyze potential determinants of preventive behavior (PB) in patients with essential hypertension (HT) and chronic ischemic heart disease (CIHD), and to establish their significance and hierarchy. Material and methods. Patients with HT (n=285) and CIHD (n=223) were studied. Questioning of all patients was performed to assess the characteristics of their PB. Differentiated multivariate analysis of activity and efficacy of PB determinants was performed in HT and CIHD patients by the method of step-by-step backward logistic regression. Results. Awareness of the cardiovascular diseases (CVD) and its prevention (odds ratio [OR] 6.08) as well as high level of general education (OR=2.29) were the most significant determinants of active PB in HT patients. Sufficient social support (OR=3.77), awareness of CVD and its prevention (OR=3.16) were the most significant determinants of active PB in patients with CIHD. Efficacy of PB in patients with HT and CIHD mostly depends on satisfaction of medical service (OR=10.2 and 6.63, respectively), social support (OR=6.25 and 10.5, respectively), adequate awareness of CVD and its prevention (OR, 6.92 and 6.64, respectively). Conclusion. PB activity and efficacy in patients with HT and CIHD depends on many contributing and impeding factors. Disregarding these factors can result in failure in preventive efforts at both individual and population levels.


725-732 492

Aim. To assess (on the basis of Russian national guidelines on arterial hypertension (HT), 2004) quality of pharmacotherapy measures among hypertensive patients observed in primary care practice. Material and methods. Data on 12 604 patients with HT (7 819 women, 4 785 men, aged 59.5±12.0 years) from 13 regions of Russia observed in primary care units during 2007 were enrolled in the study. Compliance with recommendations on decision making about pharmacotherapy need (risk category assessment) and adequacy were evaluated. Results. 64% of patients with HT had no drug prescriptions in their outpatient card in 2007. 4 880 patients from 12 604 enrolled HT patients (38.7%) had all data necessary for risk assessment. 3920 patients (31% of the whole studied group) had pharmacotherapy indications (high or very high risk). Only 819 HT patients (6.5% of the whole number of enrolled patients) had antihypertensive pharmacotherapy completely corresponding to their clinical status. Conclusion. The quality of pharmacotherapy measures carried out in primary care practice during 2007 did not conform to HT guidelines.

733-738 535

Aim. To evaluate pharmacotherapy of ST-elevation myocardial infarction (STEMI) in cardiology departments of Saratov hospitals of various types. Material and methods. The retrospective pharmacoepidemiological study was carried out with involved of 424 hospital charts of STEMI patients, discharged during the year from the cardiology department of Saratov municipal hospital (MH; n=216) and emergency cardiology department of Saratov clinical hospital (CH; n=208). Results. The real practice in the audited hospitals are not fully consistent with current guidelines for the STEMI patients management. The relationship between guidelines compliance and hospital type is clearly seen. Doctors in MH in comparison with them in CH more often prescribed respiratory analeptics (13.4% vs 5.3% , respectively), metabolic drugs (63.4% vs 37.5%, respectively) and rarer used beta-blockers (50% vs 88.9%, respectively) and thrombolytic therapy (3.7% vs 51%, respectively). In MH dipyridamole was used in 9.6% of patients as an alternative to the acetylsalicylic acid, and clopidogrel was not prescribed. At the same hospital clotting time was determined for monitoring of heparin therapy. Statins were rare used in both hospitals (26% in MH vs 40% in CH). Conclusion. The real clinical practice of STEMI patients management in Saratov hospitals are not completely consistent with current clinical guidelines. There are differences in STEMI patients therapy depending on hospital type.


739-743 990

The thrombus formation in the left ventricle (LV) cavity is a frequent complication of myocardial infarction (MI) as well as a risk factor for peripheral arterial embolism. Probability of intraventricular thrombus depends on MI location and its therapy. A case of coronary embolism in a patient with anterior MI and thrombus in the LV aneurysm is considered in details. Successful percutaneous coronary intervention (PCI) in the first 90 minutes after admission was performed. Decision to appoint a three-component antithrombotic therapy (acetylsalicylic acid, clopidogrel, warfarin) was made on the 4th day of disease onset taking into account the combination of MI, stent placement in the anterior interventricular artery and the presence of left ventricular aneurysm with parietal thrombus. Recurrence of MI developed on the 9th day of disease onset. Aspiration thromboembolectomy was performed taking into account thrombosis of two coronary arteries. Warfarin therapy was discontinued in connection with subsequent clot lysis and development of not intensive nosebleed. Subsequent MI course was uneventful. In conclusion, even in spite of the timely achievement of PCI and early reperfusion, MI course can be complicated by thrombosis of the left ventricle and subsequent development of thromboembolic complications.

744-751 917

Aim. To determine the validity of stress echocardiography by fractional reserve blood flow (FFR) as the reference method in detection of coronary arteries requiring revascularization, as well as to optimize the determination of the functional significance of coronary artery lesions in patients with multivessel coronary atherosclerosis. Material and methods. Patients (n=36) with stable angina class 2-3 with multivessel coronary atherosclerosis were included into the study. Stress echocardiography with dobutamine or exercise test (treadmill) was performed in all patients. Selective coronary angiography with subsequent evaluation of FFR was carried out in patients with a positive result of stress echocardiography. Totally 108 arteries (87 with stenosing atherosclerosis) were assessed.  Results. According to coronary angiography bi-vessel and three-vessel damages were revealed in 21 (58%) and 15 (42%) patients, respectively. Method of stress echocardiography as compared with FFR shown sensitivity — 58%, specificity — 95%, positive predictive value — 87%, positive predictive value of a negative result — 17%. Method of coronary angiography (as a method to detect significant stenosis by visual assessment of coronary artery) as compared with FFR demonstrated sensitivity 100%, specificity — 30%, positive predictive value — 42%. Conclusion. Stress echocardiography for noninvasive patient examination improves the accuracy of determination for the need and extent of revascularization.

752-756 437

Aim. To estimate metoprolol succinate effect on regulatory and adaptive status (RAS) of patients with сhronic heart failure (CHF) functional class (FC) I and arterial hypertension (HT) I-II stages. Material and methods. 51 patients with CHF FC I and HT I-II stage, (30 men and 21 women aged 52.6±1.4 yeas). Cardio-respiratory synchronism (CRS) test, 6-minute walking test, tread-mill burden test with registration of maximal oxygen consumption, 24-hour blood pressure monitoring, echocardiography and determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) blood level were performed initially and after 6 months of therapy with metoprolol succinate (dose 78.1±5.7 mg/day) in sustained-release presentation. Results. Metoprolol succinate therapy had no significant effect on RAS (there was no unidirectional dynamics of the basic CRS test parameters: a range of synchronization decreased significantly from 8.8±0.4 to 7.2±0.6 сardio-respiratory cycles per minute (in 18%; р<0.05), and duration of CRS development on the minimal boundary from 18.8±2.2 to 14.3±1.2 сardiocycles (in 24%; р<0,05); RAS index considerably did not change), myocardium structure, exercise tolerance and neuro-humoral activity. Metoprolol therapy only moderately improved left ventricle diastolic function. Conclusion. Metoprolol succinate therapy has no significant effect on RAS of patients with CHF FC I and HT I-II stages.


757-764 528

Application of dabigatran etexilate for prevention of cardioembolic complications in nonvalvular atrial fibrillation is considered. Results of randomized clinical trials on efficacy and safety of dabigatran in various doses are discussed. Besides, a comparison of dabigatran and varfarin therapies is presented taking into account pharmacoeconomic data. Recommendations on dabigatran dosing are considered to do intervention more effective and safer.

765-769 568

Up to date principles of diagnostics and treatment of infective endocarditis are presented. Advantages of the special highly-sensitive concentrated media over the standard low-sensitive media for etiological verification of the infective agent are discussed.


770-774 891

The main objectives and strategies for treatment of atrial fibrillation (AF), one of the most common cardiac arrhythmia, are seen. A combination of strategies for heart rate control in patients with atrial fibrillation receiving rhythm-controling therapy is preferred at present, according to current guidelines. Amiodarone, one of the most effective anti-arrhythmic drugs with an extensive evidence base, remains the drug of reserve because of serious side effects. A new drug, dronedarone, has electrophysiological properties attributable to all four classes of antiarrhythmic drugs. According to meta-analysis of randomized clinical trials dronedarone is inferior to amiodarone in prevention of AF recurrences, but it is superior to amiodaron in safety. However , in 2011 dronedarone was included in the Food and Drug Administration (FDA) list of drugs that require further analysis in connection with appearance of the new information about its safety.


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