Rational Pharmacotherapy in Cardiology

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Vol 6, No 1 (2010)
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5-8 188

In the issue.


9-19 626

Aim. To study efficacy of moderate-intensity physical training (PT) and evaluate lipid-lowering therapy in patients with ischemic heart disease (IHD) after acute coronary events in real practice.

Material and methods. A total of 392 patients survived during last 3-8 weeks myocardial infarction, unstable angina or myocardial revascularization were included into the study. Inclusion of patients with stable angina pectoris after hospital treatment was also possible. Patients were randomized to the main (n=197) and control (n=195) groups. Patients of the main group received moderate-intensity PT. All patients received beta-blocker, nitrate, ACE inhibitors and acetylsalicylic acid. Frequency of lipid-lowering therapy prescription and its efficacy were assessed in both groups. Duration of the study was 1 year. The efficacy of interventions was evaluated by the dynamics of plasma lipid levels, results of bicycle ergometry and clinical end points.

Results. We observed increase in exercise test duration by 32% (p<0.001), efficiency of heart work by 12% (p<0.05), decrease in frequency of angina attacks by 51% (p<0.001) in the main group. Decrease in total cholesterol (TC) by -3.6% (p<0.05) and increase in high density lipoproteins (HDL) cholesterol by 12.3% (p<0.01) were also observed. Differences in the dynamics of physical tolerance, levels of TC, HDL cholesterol and the TC/HDL cholesterol ratio were significant at intergroup comparison. Lipid-lowering drugs implementation was inadequate in both groups. Target plasma levels of low density lipoproteins (LDL) cholesterol were reached in no one group. We registered less cardiovascular events in the main group in comparison with control one (14% vs 28%, respectively) as well as hospitalizations due to IHD (11% vs 18%, respectively) and number of days of disability (2.2 vs. 4.2 days per patient annually, respectively). Differences in mentioned clinical end point rates were significant between groups (p<0.05).

Conclusion. Results of the study shown PT efficacy in patients with IHD after cardiovascular events. Lipid-lowering therapy is conducted inefficiently in patients with IHD in real practice. It is advisable to introduce PT program in real practice as well as adequate pharmacotherapy.

20-28 2239

Aim. To compare efficacy of ramipril generic Hartil® (Egis) to original drug Tritace® in patients with arterial hypertension (HT) of 1-2 degree and high cardiovascular risk, and to evaluate target blood pressure (BP) achievement when taking each drug separately and in combination with the calcium channel blocker amlodipine.

Material and methods. A total of 27 patients (14 men, 13 women) with HT of 1-2 degree and high risk due to combination of HT with ischemic heart disease, diabetes or previous stroke were included in an open randomized crossover study. Each patient received generic and original ramipril during 6 weeks by turns. Antihypertensive efficacy (the target BP level <130/80) was evaluated every 2 weeks. In case of treatment inefficiency a dose was doubled and amlodipine (Cardilopin, Egis) was added. After 6 weeks of treatment with the first drug of ramipril the second one was administered.

Results. After 6-week Hartil treatment the mean systolic BP (sBP) decreased by 20,0 mm Hg compared to the baseline level, while at Tritace treatment – by 22,2 mm Hg. The mean diastolic BP (dBP) decreased by 10,8 and 8,6 mm Hg respectively (differences between the drugs were insignificant). Twenty patients treated with Hartil and 16 patients treated with Tritace required Cardilopin prescription. The target BP<130/80 was achieved in 10 patients (38,5%) who took Hartil and in 13 patients (50%) treated with the original ramipril (differences between the drugs were insignificant).

Conclusion. Therapeutic equivalence of the generic ramipril Hartil and the original drug Tritace was demonstrated. Monotherapy efficacy was low in high-risk patients with HT of 1-2 degree, and combined therapy with two antihypertensive drugs was effective in 40-50% of cases.

29-36 553

Aim. To study antihypertensive efficacy and safety of valsartan (Diovan, Novartis Pharma) as well as patient’s compliance to the mono- or combined valsartan based therapy in smoking vs non-smoking hypertensive patients.

Material and methods. It was a prospective multicenter observation study. 114 doctors from 81 medical institutions of Russia participated in the study. 650 hypertensive patients (41,2% of smokers and 58,8% of non-smokers; age 53,9±0,4 y.o. in average) were included in the study. The evaluation of therapy efficacy was based on analysis of systolic (SBP) and diastolic (DBP) blood pressure (BP) changes and of patient number who answered to the treatment and reached BP target level. Safety and compliance of the treatment also was analyzed. The initial valsartan dose was 80 mg OD and may be increased (up to 320 mg OD) by doctor for achievement of BP target level. A combination of the valsartan with hydrochlorothiazide was also allowed. Amlodipine (5-10 mg/d) or any other antihypertensive also may be added if necessary.

Results. Significant decrease of SBP and DBP was observed in each group between the 1st and 5th visits. SBP decreased by 37,5 mm Hg (р<0,01) in smoking patients and by 37,6 mm Hg (р<0,01) in non-smoking ones. DBP decreased by 18,5 mm Hg (р<0,01) in smoking patients and by 15,9 mm Hg (р<0,01) in non-smoking ones. Differences in SBP and DBP changes were not significant between groups. Target BP level (<140/90 mm Hg) was reached in 96,2% of smokers and in 96% of non-smokers. 99% of smoking patients and 96,1% of non-smoking ones responded to valsartan based therapy according to defined criteria.

Conclusion. Similar antihypertensive efficacy and safety of valsartan mono- and combined therapy was found out in smoking and non-smoking hypertensive patients.

37-41 389

Aim. To evaluate influence of long-term monotherapy with nebivolol on blood pressure (BP) (office BP; self-monitoring BP, pre-trip BP monitoring, ambulatory BP monitoring (ABPM)) and metabolic blood profile in locomotive crew staff with newly diagnosed arterial hypertension (HT).

Material and methods. Locomotive crew engineers and their assistants (n=50; age 20-55 y.o.) with newly diagnosed HT 1-2 degree with moderate-to-high cardiovascular risk were included into the open prospective uncontrolled study. The study duration was 12 months. The office BP level, heart rate were evaluated initially, in 12 weeks and 12 months of treatment; pre-trip BP level – one time per month; ABPM and blood biochemical tests (glucose and lipid profile) - initially and in 12 months of therapy. Data of BP self-monitoring, nebivolol treatment compliance and safety was also evaluated.

Results. Long-term monotherapy with nebivolol allowed reaching the target level of office BP, self-monitoring BP, ABPM. Nebivolol provided BP control both in working days and in week end. Efficacy of nebivolol monotherapy was 88%. Nebivolol therapy improved basic ABPM indicators (load pressure, variability, daily rhythm), pulse BP, heart rate. Nebivolol had no significant negative metabolic effects, 78% of patients demonstrated sufficient compliance with nebivolol treatment. Adverse reaction (bradycardia) was observed in 2 (4%) patients.

Conclusion. Nebivolol has high antihypertensive efficacy, metabolic neutrality and good safety profile in the locomotive crew staff with newly diagnosed HT.

42-47 353

Aim. To study purine metabolism and lipid peroxidation in patients with acute myocardial infarction with ST segment elevation (STEMI) in dependence on severity of acute heart failure (AHF). To evaluate effects of thrombolytic therapy on purine metabolism and lipid peroxidation.

Material and methods. 91 patients (age 60,8±1,2 y.o.) with STEMI and AHF (Killip 1-3) was included into the study. Patients were randomized into 3 groups in dependence of AHF severity. Markers of purine metabolism (activity of 5’- nucleotidase, xantineoxidase and uric acid level) and lipid peroxidation (superoxide dismutase and catalase activity, superoxide-anione radical level) were evaluated.

Results. Purine metabolism activity increases, antioxidant and prooxidant balance disturbs at the condition of energy deficiency. AHF progression leads to increase in xanthine oxidize activity, urinary acid level and lungs edematization. Thrombolytic therapy increases antioxidant activity (response on reperfusion), but does not lead to purine metabolism stabilization.

Conclusion. Thus, severity of heart failure in patients with STEMI correlates with disorders of purine and lipid metabolism. Thrombolytic therapy leads to rising in antioxidant protection, but does not lead to stabilisation of purine metabolism.

48-53 440

Aim. To study influence of the fixed bisoprolol (BIS) + hydrochlorothiazide (HCT) combination on blood pressure (BP) level and a blood flow in middle cerebral artery in patients with a arterial hypertension (HT), 1 degree.

Material and methods. 18 patients with HT 1 degree (7 men, 11 women; age 50,1±5,7 y.o.) were included in the non-comparative open study. All patients received a combination of selective beta1-adrenoblocker (BIS 2.5-5 mg) and diuretic (HCT 6,25 mg). Initially and in 12 weeks of the treatment all patients had a standard clinical examination, ambulatory BP monitoring, ultrasonography of mesencephalic arteries for evaluation of the cerebrovascular blood flow reactivity.

Results. The target BP level (<140/90 mm Hg) in 12 weeks of the treatment (12 patients received BIS 5 mg/HCT 6,25 mg, 6 patients - BIS 2,5 mg/HCT 6,25 mg) was reached in 100% of patients. Besides, significant increase in cerebral blood flow reactivity was found in tests with hyper- and hypoventilation.

Conclusion. The fixed BIS/HCT combination has high antihypertensive and vasoprotective efficacy.

53-60 511

Aim. To evaluate effects of Actovegin (deproteinized hemoderivative) on vasomotor and metabolic functions of microvascular skin endothelium in healthy volunteers during acute pharmacological test.

Material and methods. 24 healthy male volunteers, aged 18-26 years (21,9±2,7), received Actovegin i.v. during 2 hour infusion through the left cubital vein. Right forearm skin laser Doppler flowmetry (LDF) with wavelet analysis of the microcirculatory oscillations was used initially and after 2 hour Actovegin infusion to assess microvascular endothelial responses (microcirculatory blood flow changes) to Actovegin. Saline infusion in 5 subjects used for control data receiving.

Results. Actovegin significantly increased in maximal amplitude endothelial rhythm (at a frequency of 0.01 Hz) by 76% (p<0,001) and functional contribution of microvascular endothelium in the overall level of tissue perfusion by 79% (p<0,001). Control saline infusion resulted in reduction of these indices by 52 and 54%, respectively. Actovegin also increased significantly myogenic rhythm amplitude (vascular tone reduction) by 35% (p<0,05) and decreased diastolic blood pressure by 3 mm Hg (p=0,076), which is likely result of increased endothelium nitric oxide release.

Conclusion. Microcirculatory oscillations at the frequency of 0.01 Hz reflect both vasomotor and metabolic function of microvascular endothelium. Actovegin improves oxygen and glucose tissue utilization as well as increases nitric oxide production with microvascular smooth muscle tone reduction.

61-67 401

Aim. To evaluate the cardioprotective effects of ACE inhibitor, ramipril and angiotensin II receptor antagonist (ARA), valsartan at the cardiovascular continuum (CVC) stages.

Material and methods. 577 patients were examined. Patients with arterial hypertension (HT) (n=283; group 1), with metabolic syndrome (n=137; group 2), with HT associated with ischemic heart disease (n=157; group 3) were randomized into treatment subgroups A (ramipril) and B (valsartan). All patients had clinical examination, transthoracic echocardiography with remodeling indexes calculation, ambulatory blood pressure monitoring initially and after 6 months of therapy.

Results. Valsartan had priority in prevention of early cardiac remodeling (reduction in left ventricular (LV) hypertrophy and myocardial stress, improvement of functional heart parameters) at early CVC stage (HT, metabolic syndrome). On the other hand ramipril had priority at advanced stage of CVC (reduction in systolic diameter-thickness ratio, LV hypertrophy, myocardial stress and myocardial stiffness). At the advance stage of CVC valsartan treatment also resulted in significant reduction in LV hypertrophy and myocardial stress, improvement in cardiac remodeling functional parameters but had no effect on LV diameter-thickness ratio.

Conclusion. The ARA treatment is preferred at early CVC stage for better cardioprotection.

68-72 396

Aim. To find out similarities and differences between various evolutionary stages of low rennin hypertension (LRHT), and to develop its diagnostic criteria.

Material and methods. Patients (n=190) with LRHT and the high cardiovascular risk were included into the study. All patients received ACE inhibitor, enalapril 10 mg twice a day, during 4 weeks. Before and after enalapril treatment plasma renin activity (PRA) and plasma aldosterone level (PAL) were determined by radioimmunoassay method in active patients. 24-hour urinary excretion of epinephrine (UEE) and norepinephrine (UENE) was also determined by laser flowmetry.

Results. Three forms of LRHT were defined among all patients: 1) patients (n=144) with essential LRHT had stimulated renin, eu- or hyperaldosteronism without adrenal hyperplasia; 2) patients (n=14) with transient LRHT had nonstimulated renin, eualdosteronism, presence or absence of adrenal hyperplasia; 3) patients (n=32) with the primary idiopathic hyperaldosteronism had nonstimulated renin, hyperaldosteronism and adrenal hyperplasia.

Conclusion. Three stages of LRHT evolution are found out. They have similar pathogenesis and different expression of morphofunctional changes in the juxtaglomerular complex and in the adrenal cortex as well as different respond to enalapril test (20 mg/daily).

73-76 289

Aim. To evaluate a prevalence of cardiovascular risk factors among physicians, awareness about their own cardiovascular risk factors as well as their knowledge about actual clinical guidelines.

Material and methods. 71 physicians (age 44,7±9,7 y.o.) practicing in city of Nizhni Novgorod were included into the study. They were examined to reveal cardiovascular risk factors and interviewed about main methods of cardiovascular diseases treatment and prevention.

Results. Arterial hypertension (HT) prevalence among physicians was 38%, awareness about HT occurrence - 28%, own blood pressure control - 11% of physicians. The prevalence of hypercholesterinemia was 44%, 65% of physicians did not know their own plasma cholesterol level. Physicians had obesity or overweight in 21% and 42% respectively. 91% of physicians demonstrated knowledge about cardiovascular risk factors, 90% and 79% of them were sure regarding possibility to achieve target blood pressure and lipid levels, respectively.

Conclusion. High prevalence of HT, hypercholesterinemia, and overweight were found out among physicians despite of their knowledge of actual clinical guidelines on cardiovascular diseases therapy and prevention.


77-83 873

Author discusses antiatherosclerotic effects of dihydropyridine calcium channel blocker, amlodipine, in patients with coronary artery disease. Results of randomized clinical trials PREVENT (2000), CAPARES (2000), CAMELOT (2004) and ENCORE II (2009) are analyzed.

84-88 351

The problem of antiplatelet drug choice in patients with atrial fibrillation is discussed. Authors give special attention to new alternative drugs for prevention of thrombotic complications apart from old known antiplatelet drugs.


89-94 338

Advantages of combined therapy of patients with arterial hypertension are considered. Special attention is paid to usage of ACE inhibitor and calcium antagonist combination.

95-102 479

The evidence basis and advantages of the lisinopril usage in a clinical practice as antihypertensive drug are presented. Special attention is paid to organoprotective lisinopril effects and lisinopril implementation at special clinical conditions (chronic obstructive pulmonary disease comorbidity, elderly patients, and concomitant liver diseases). Pharmacoeconomic aspects of lisinopril usage in arterial hypertension are also considered.

103-107 645

Data of the evidence based medicine about bisoprolol treatment of patients with cardiovascular diseases (arterial hypertension, ischemic heart disease, chronic heart failure, rhythm disorders) are presented. Implementation of bisoprolol generics as well as bisoprolol usage in smoking cardiovascular patients is also discussed.



117-121 262
Cardiology: reality and prospective. Results of Russian National congress of cardiology.
122-123 174

Uniform Requirements for Biomedical Publication: Editorial Comments.


129-130 211

Boris Alexeevich Sidorenko. To the 70-th anniversary of the birth.

131-132 189

Russian National congress of cardiology in October 5-7, 2010.

133 191

Event schedule of Society of Cardiology of the Russian Federation for 2010.

133 202

Briefing note about activity of editorial board of “Rational Pharmacotherapy in Cardiology” in 2009.

134-135 167

Press-release of “Purple heart” National award.

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