Rational Pharmacotherapy in Cardiology

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Vol 4, No 1 (2008)



6-9 497

Aim. To compare prescriptions of antihypertensive drugs in town of Orel with these in Russia in the whole.

Material and methods. 23 cardiologists and 78 internists of Orel town were questioned about antihypertensive drug prescriptions in 2006.

Results. ACE inhibitors, diuretics, beta-blockers, calcium channels antagonists were prescribed in order of popularity decreasing as mono- or combined therapy. About 70 % of doctors prescribed pharmacotherapy, which cost 100 to 500 rubles per months. Not rational combinations were prescribed in 4,7% of cases. Only 55,4% of respondents used blood pressure level less than 140/90 mm Hg as a target one.

Conclusion. Antihypertensive drug prescription for mono- or combined therapy was in accordance to modern guidelines but in the some cases did not meet them.


10-13 385

Aim. To estimate effects of fosinopril and atenolol on autonomic regulation of heart in patients with arterial hypertension (HT) on the basis of spectral characteristics of heart rate variability (HRV).

Material and methods. 49 patients (46±7 y.o.) with untreated or inadequately treated HT without end organ damages and associated clinical conditions were involved in the study. Heart rhythm was registered during passive orthostatic test with spontaneous breath within 10 min for each stage of the test. HRV was estimated by parametrical method based on autoregression model. Frequency power of HRV spectrum (ms2 ) in high-frequency (HF: 0,15-0,4 Hz) and low-frequency (LF: 0,04-0,15 Hz) ranges was calculated as well as the total power of a spectrum (ТР).

Results. Fosinopril and atenolol reduced in blood pressure levels similarly, atenolol as well reduced in heart rate. Fosinopril and atenolol changed power of LF-range in comparable decreasing manner in upright position. Fosinopril therapy resulted in the same changes with power of HF-range. Atenolol increased power of HF-range in horizontal position and had no effect in upright position. There were not dynamic in TP during treatments.

Conclusion. Fosinopril and atenolol have similar effects on the central mechanisms of autonomic heart regulation and HRV, though atenolol effect on sympathetic-parasympathetic balance is more prominent.

14-18 953

Aim. To compare effects of 12-month monotherapy with nebivolol, enalapril and indapamide on blood pressure (BP), left ventricular hypertrophy and quality of life in the locomotive engineers and their assistants with stress-associated hypertension at the work place (HTwp).

Material and methods. 96 locomotive engineers (20- 53 y.o) and their assistants with HTwp were observed. The patients were randomized to receive nebivolol (1 group), enalapril (2 group) or indapamide (3 group). 24-hour BP monitoring, echocardiography and quality of life interview with SF–36 questionnaire were performed at the start and after 12 months of the treatment.

Results. Long-term therapy lead to achievement of target BP level, improved quality of life and reduced in left ventricular hypertrophy in patients with HTwp. Nebivolol reduced systolic “BP load” more significantly than indapamide did, exerted favorable influence on circadian BP rhythm and reduced heart rate. Monotherapy with nebivolol showed benefits in effect on quality of life.

Conclusion. Nebivolol has some advantages in comparison with indapamide and enalapril in antihypertensive therapy of patients with stress-associated HT.

19-24 940

Aim. To compare antiplatelet effect of two acetylsalicylic acid medicines, Acecardol ("Synthesis Co. Ltd", Russia) and Aspirin cardio («Bayer AG», Germany), in patients with arterial hypertension (AH) 1-2 stage with increased risk of cardiovascular events.

Material and methods. The study was double-blind, randomized, cross-over one. 32 hypertensive patients (12 men and 20 women) aged 59,4±14,4 y.o. were included in the study. They took investigated ASA medicines one after another during 4 weeks each. Antiplatelet efficacy of ASA medicines were estimated by effects on spontaneous and ADP-induced platelet aggregation at every visit.

Results. 4-week therapy with both ASA medicines did not have significant effects on spontaneous platelet aggregation and the aggregation induced with low ADP concentrations (0,5 and 1,0 µM). However platelet aggregation induced with ADP in concentration of 2 µM was significantly reduced by therapies. There were not significant inter-group differences.

Conclusion. ASA generic medicine Acecardol ("Synthesis Co.Ltd.", Russia) and original medicine Aspirin cardio («Bayer AG», Germany) are equivalent on antiplatelet effect.

27-31 338

Aim. To study effect of coronary revascularization in combination with inotropic stimulation and myocardial unloading on prognosis in elderly patients with myocardial infarction (MI) complicated with heart failure (HF).

Material and methods. 149 elderly patients with ECG picture of acute MI with ST segment elevation and HF symptoms were included into the study. All patients received standard therapy. According to the additional therapeutic maneuvers patients were split into four groups: 18 patients treated with percutaneous transluminal coronary angioplasty (PTCA) combined with inotropic levosimendan (LS) therapy; 20 patients with PTCA only; 22 patients treated with levosimendan (LS) only; control group - 89 patients with standard therapy without PTCA or LS.

Results. Combination of PTCA and LS in elderly patients with acute MI complicated by HF had advantages in comparison with PTCA or LS applied separately or not applied at all. Combined therapy with PTCA and LS resulted in more prominent improvement of left ventricle systolic function, increase in exercise tolerance and more effective prevention of cardiac remodeling and was safe.

Conclusion. Combined therapy with PTCA and LS is more effective than separate usage of these methods in elderly patients with MI complicated with HF.

33-38 741

Aim. To study association between stroke and gene polymorphism of angeotensin converting enzyme (ACE), angeotensin II type 1 receptor (ATR1), apolipoprotein СIII (APO CIII), apoproteine Е (APO E), methylentetrahydrofolate reductase (MTHFR), fibrinogen (Fb), endothelial NO-synthase (NOS3) in arterial hypertension (HT).

Material and methods. Molecular genetic analysis by polymerase chain reaction was done in 41 patients with HT, who experienced first episode of acute disturbances of cerebral blood circulation (ADCBC).

Results. Stroke rate in patients with HT is associated with A1166C of ATR1 gene polymorphism, G-455A of Fb gene polymorphism and C677T of MTHFR gene polymorphism. The high risk markers are C-allele of ATR1 gene, -455А allele and AA genotype of Fb gene, 677T allele of MTHFR. The A-allele and genotype AA of ATR1 gene, G-445 allele of Fb gene, С677-allele and CC genotype of MTHFR gene play protective role against ADCBC in HT.

Conclusion. It is established an association between gene polymorphism of some molecules and ADCBC in HT.

39-43 526

Aim. To determine the potential of tissue Dopplerography (TDG) for early diagnosis of functional myocardial disorders in patients with arterial hypertension (HT).

Material and methods. 66 patients with HT were examined. Clinical examination, 24-hour ambulatory blood pressure monitoring, two-dimensional- and Doppler-echocardiography of transmitral blood flow, TDG of mitral annulus, determination of blood level of brain natriuretic peptide (BNP) were performed.

Results. Regional disturbances of diastolic myocardial function are detected in patients with HT and normal transmitral blood flow. These disturbances are more expressed in left ventricle (LV) remodeling. The LV remodeling is also connected with disorders of the longitudinal myocardial contractile systolic function of the inferior wall. These disorders are more expressed in patients with HT and chronic heart failure (CHF). The average ratio of peak rates of the early transmitral blood flow and the diastolic myocardial movement (E/Ea), as well as the average level of BNP confirmed the moderate increase in end-diastolic pressure in LV.

Conclusion. Regional disorders of diastolic myocardial function in patients with HT are detected before structural changes of LV even in normal transmitral blood flow. The LV remodeling is related to the disorders of diastolic and regional systolic myocardial function, which are accompanied with increase in BNP level. At the same time increased BNP level is especially related with increased E/Ea ratio, which is more earlier predictor of CHF in hypertensive patients.

44-48 548

Aim. To compare antihypertensive efficacy of АТ1 receptors blocker (losartan) and ACE inhibitor (enalapril), including their combinations with hydrochlorothiazide.

Material and methods. 60 patients (30-65 y.o.) with arterial hypertension (HT) of stages 1-3 were involved in 12-week opened comparative randomized study. Patients of group-I (n=30) received losartan, patients of group-II (n=30) - enalapril. Blood pressure (BP) changes assessed on the basis of clinical measurements and ambulatory monitoring. Microalbuminuria (MAU) levels, plasma aldosterone levels and plasma renin activity were estimated.

Results. Target BP levels were reached in 76,6% of patients in group-I and in 73,3% of patients in group-II. Among patients with moderate HT of stage 2 (n=50) target BP levels were reached in 96% of patients in group-I and in 72% of patients in group-II. Patients of both groups had positive changes in BP levels according to ambulatory BP monitoring. Significant reduction in MAU level and uric acid plasma concentrations were observed.

Conclusion. Losartan (Losap, Zentiva) and losartan combination with hydrochlorothiazide (Losap-plus, Zentiva) demonstrated antihypertensive efficacy comparable with this of enalapril as well as nephroprotective features.

51-55 354

Aim. To assess the microalbuminuria (MAU) and vascular wall elasticity in patients with essential hypertension (HT) and evaluate the possibilities to reduce in fatal cardiovascular risk due to lisinopril (Listril, Dr Reddy’s) therapy.

Material and methods. 42 patients (60,3±0,83 y.o.) with HT were involved in the study. Pulse wave velocity was estimated by volume sphygmography. MAU levels were detected with micral-test (Roche Diagnostics, Germany). Patients received lisinopril as a first-step antihypertensive drug, if necessary the dose of lisinopril was increased or amlodipine was added. The treatment lasted for 12 weeks.

Results. MAU was revealed more often in patients with increased body mass index as compared with whole population of hypertensive patients. MAU was associated with increased vascular wall stiffness. Lisinopril therapy during 4 weeks allowed to reach target level of blood pressure (BP) in 42,9% of patients and decreased in MAU level by 54,5%. Therapy continuation during 12 weeks allowed to reach target level of BP in 90,4% of patients and reduce in fatal cardiovascular risk by 36,6%.

Conclusion. Lisinopril therapy resulted in significant reduction in BP, MAU and fatal cardiovascular risk in patients with HT.

56-61 986

Aim. To evaluate the effect of metoprolol tartrate on blood pressure (BP) and cognitive function in young to middle aged patients with essential hypertension (HT).

Material and methods. 40 men (age of 49,0±1,9 y.o.) with HT of I-II stage not taking antihypertensive medication regularly were enrolled into the study. All patients were given metoprolol tartrate (start dose 50-100 mg/d). Variables of 24-h BP monitoring and clinic BP, left ventricular mass index (measured by echocardiography) and characteristics of cognitive function (memory, attention, thinking and neurodynamic) were assessed at the start, after 1 and 6 months of therapy.

Results. Good and satisfactory antihypertensive effect was achieved in 75% of hypertensive patients with metoprolol (186,6±13,4mg/d) monotherapy. Metoprolol significantly decreased maximum day-time systolic and diastolic BP, maximum night-time diastolic BP, mean day-time systolic and night-time diastolic BP, time-index, load-index and variability-index for night-time diastolic BP, day-time and night-time pulse BP. Left ventricular mass index reduced significantly (p<0,0001). After 6 months of therapy significant improvement of memory, attention, thinking and neurodynamic was observed

Conclusion. Metoprolol had beneficial effect on cognitive function in hypertensive patients, which demonstrate its cerebroprotective properties in addition to antihypertensive action. Metoprolol can reduce the risk of dementia in young to middle aged patients with HT.

62-66 441

Aim. To study the effect of the long-term antihypertensive monotherapy with indapamide (Arifon Retard, 1,5 mg/d), metoprolol tartrate (Egilok Retard, 50 mg/d) and combined therapy with indapamide and perindopril (Noliprel Forte, 1 tab/d: perindopril 4 mg and indapamide 1,25 mg) on pulse wave velocity (PWV), cardio-ankle vascular index (CAVI) and the sympathetic system activity.

Material and methods. 88 patients, aged 30-59 y.o. (32 normotensive patients, 56 with arterial hypertension [HT] of 1-2 grades) were examined. Biological age (BA) was determined by the linear regression and the vascular wall age (VWA) was estimated with the use of volume sphygmography (“VaSera-1000”, “Fucuda Denshi”, Japan). 39 patients with HT were randomized into 3 parallel groups with studied therapies lasted for 6 months. PWV, CAVI of the vessels of elastic, muscular and mixed types, blood pressure, measured in upper and lower extremities and heart rate variability (HRV) were determined before and at the end of the therapies.

Results. BA and VWA were elevated in all of patients with HT as compared with normotensive patients. The reduction in PWV and CAVI of the vessels of elastic and mixed types, HRV increase were found in patients with Arifon Retard monotherapy. Monotherapy with metoprolol significantly improved HVR without any influence on the vascular remodeling. Noliprel Forte significantly decreased in blood pressure in the upper and lower extremities, PWV and CAVI of the vessels of all types, decreased in VWA and increased in parasympathetic drive.

Conclusion. Long-term therapy with Arifon Retard and Noliprel Forte resulted in decrease in vascular remodeling and increase in HRV simultaneously with significant antihypertensive effect in patients with HT. Metoprolol low doses therapy resulted in normalization of autonomic drive independently on antihypertensive action.

67-75 467

Aim. To compare the effects of long-term therapy with angiotensin-II receptor antagonist losartan, alone or in combination with hydrochlorothiazide, and amlodipine treatment on left ventricular morpho-functional variables and blood pressure (BP) in hypertensive patients.

Material and methods. 25 women and 27 men (average age 52,7±1,2 y.o.) with essential hypertension (1-2 grade) and left ventricular hypertrophy (LVH) were included into the study. After 3 week washout period the patients were randomized in 2:1 fashion to receive either losartan (n=34) or amlodipine (n=17). In 17 patients with insufficient response to losartan monotherapy (50-100mg/day) hydrochlorothiazide (12,5mg) was added to losartan (50mg) 4 weeks later. The daily dose of amlodipine was increased from 5 to 10 mg in 10 patients. At baseline and after 24 weeks of treatment 24-h BP monitoring and echocardiography (with evaluation of cardiac chamber dimensions, inter-ventricular septal and posterior wall thickness, left ventricular mass index -LVMI) were performed.

Results. 4-week losartan treatment significantly decreased clinic BP (-14,1±2,2/8,2±1,4 mm Hg, p<0,01), mean daily systolic and diastolic BP (-15,1±2,4 mm Hg and -8,9±1,7 mm Hg , p<0,001), mean day-time and night-time BP and systolic and diastolic BP load in 34 patients. Addition of hydrochlorothiazide induced a further decrease of mean night-time BP, pulse BP, improved circadian rhythm and normalized BP in 75% of patients compared with 50% in losartan alone. Significant decrease of clinic BP (-24,1±3,6/15,2±2,3, p<0,01), mean daily systolic and diastolic BP and BP load were noticed at 24 week of amlodipine treatment. Circadian BP rhythm didn’t change; night-time decrease of BP was insufficient. Antihypertensive efficacy was similar in both groups. Losartan, alone or combined with hydrochlorothiazide, caused regression of LVH in all patients, normalized geometry of left ventricle in 33% of patients and improved left ventricular diastolic function in 88,2% of patients. LVMI decreased due to reduction of wall thickness. Changes in LVMI, relative wall thickness and diastolic function in losartan group were greater than those obtained in amlodipine group.

Conclusion. Losartan, administered alone or combined with hydrochlorothiazide, has the greater effect on LVH, geometry and diastolic function of left ventricle compared with amlodipine. These results give evidence that losartan has cardioprotective and possibly other pleiotropic effects.

76-80 520

Aim. To study gender differences of endothelial vasomotor function and pulse wave velocity (PWV) in patients with arterial hypertension (HT) and to evaluate effects of amlodipine (Normodipine, Gedeon Richter) on these parameters.

Material and methods. 57 patients with HT of 1-2 stages were involved in the study. Patients were randomized to 4 groups: women under 50 y.o. (group 1), women older than 60 y.o. (group 2), men under 50 y.o. (group 3) and men older than 60 y.o. (group 4). Endothelium vasomotor function was estimated by ultrasonography. PWV was estimated by volume sphygmography. Patients received antihypertensive therapy with amlodipine during 12 weeks.

Results. The lowest levels of systolic blood pressure (BP), normal endothelium function and PWV were observed in women with normal menses. The highest levels of pulse BP were found in menopausal women. Amlodipine monotherapy had better antihypertensive effect in women than in men. BP target levels were reached in 60% of amlodipine treated women. Besides amlodipine improved vascular endothelial function.

Сonclusion. Disorders of endothelial function and PWV begin later in women than in men, however after menopause the rate of these disorders development in women is faster than in men of similar age.


81-86 462
The main indications to statins and principles of statin usage on the basis of International Guidelines are discussed. Problem of statin choice and problem of equivalence of generic drugs to original drugs are studied.
87-90 359
Primary prevention of diabetes in persons with high cardiovascular risk is an actual problem. Results of DREAM trial are discussed. Influence of ACE inhibitor, ramipril, on risk of diabetes onset in patients with pre-diabetes and low cardiovascular risk is focused. Metabolic effects of other groups of antihypertensive drugs and their ability to prevent diabetes onset are compared. Ramipril three years therapy resulted in normalization in glucose level but did not have effect on frequency of diabetes onset. Change in life-style and regular usage of ACE inhibitor, ramipril, can contribute in normalization of glycemia level in patients with combination of pre-diabetes and arterial hypertension.


92-120 324
The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

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