Rational Pharmacotherapy in Cardiology

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Vol 2, No 1 (2006)
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4-10 336

Aim. To study psychological status and influence of antihypertensive therapy (AHT) on it in Chernobyl nuclear power plant (NPP) accident consequences liquidators, who suffer arterial hyper-tension (AH), with controlled treatment compared to the standard treatment in out-patient clinic. Material and methods. 81 liquidators with AH (all men) were included into open compara-tive randomized study. Study duration was 12 months. Patients were randomized into main group (MG) and control group (CG). Patients of MG received strictly regulated stepped AHT based on ACE inhibitor spirapril 6 mg daily (Quadropril®, Pliva-AVD), hypothiazide was added if necessary (12.5-25 mg daily) and afterwards – atenolol (12.5-100 mg daily). In CG AHT and its correction was set by physician in polyclinic. Brief multifactor questionnaire for personality analysis was used to study psychological status. Results. 57 patients completed the study, 28 in MG and 29 in CG. In MG target blood pres-sure (BP) levels were reached in 22 (78.6%) patients, in CG – in 11 (38%) patients (p<0.01). The main feature of psychological status of liquidators with AH was hypochondriac, depressive and anxious disorders. Controlled AHT made it possible to reach improvement in psychological status, i.e. growth of optimism and activity of patients, more often, than standard treatment in out-patient clinics. Increase in number of patients with pronounced anxious changes was observed in CG. Effi-ciency of AHT in liquidators with AH is connected with severity of depressive disturbances: in subgroups with inefficient treatment patients had the highest level of depression. In liquidators with AH, possessing neurotic disturbances, spirapril was efficient both as monotherapy, and in combina-tion with diuretic hydrochlorothiazide and beta-blocker atenolol. Conclusion. Controlled AHT in liquidators with AH has advantages over standard treatment in out-patient clinic and results in more frequent target BP level achievement as well as more fre-quent psychological status improvement.

11-17 375

Aim. To assess an influence of ACE inhibitor enalapril on daily profile of blood pressure (BP) in comparison with uncontrolled antihypertensive therapy in patients with metabolic syndrome (MS). Material and methods. 41 patients with MS were included in opened parallel controlled study. Patients were randomized into two groups. Patients of the first group received enalapril (Enam, Dr. Reddy’s) 10 mg daily with the further titration of the dose up to 20 mg daily. Patients of the second group took previous antihypertensive therapy (15% of patients took ACE inhibitors, 15% - beta-blockers, 15% - diuretics and 20% - combined therapy). Study duration was 12 weeks.  Continuous ambulatory monitoring of BP (AMBP) was applied in all patients at the beginning and at the end of the study. Results. Enalapril therapy during 3 months in average dose of 17±1 mg daily reduced average 24-hour systolic, diastolic and pulse BP by 10, 8 and 14% respectively. These changes were significant in comparison with these in patients with uncontrolled therapy (3,7, 3,8 and 4% respectively). Enalapril reduced also average night systolic, diastolic and pulse BP (11, 11 and 10% respectively). In patients receiving uncontrolled therapy these changes were 3-4%. Two times decrease in BP burden in daytime and nighttime were observed while BP burden remained unchanged in uncontrolled therapy during both periods. Thanks to enalapril monotherapy a number of non-dippers reduced in more than two times due to recovering of night BP decrease (40% before and 15% after treatment). These changes were less expressive in the second group (45% before and 30% after treatment). Conclusion. Enalapril in average dose can be widely used for correction of daily BP profile in patients with MS.

18-24 501

Aim:  to evaluate efficiency and safety of the combined antihypertensive drug Lozap Plus (50 mg losartan, 12,5 mg hydrochlorothiazide) in patients with arterial hypertension (AH) of I-III grade with high and very high cardiovascular risk. Material and methods: 30 patients with AH of I-III grade (13 men and 17 women aged 51.9±1.9) were observed. Patients received Lozan Plus (Zentiva, Czech Republic) 1 time in the morning during 12 weeks. Ambulatory blood pressure monitoring (ABPM), echocardiography, biochemical blood analysis were carried out, microalbuminuria (MA) was determined, quality of life was assessed. Results: After 2 weeks of therapy decrease in office systolic blood pressure (BP) was observed, and after 4 weeks - in diastolic BP. After 12 weeks of treatment decrease in BP became more significant. Target systolic and diastolic BP was reached in 83.3% and 90% of patients respectively. Decrease in systolic BP was observed in 24 hrs. (from 141.9±1.9 to 128.6±0.8 mmHg, p<0.001), in daytime (from 146.8±2.6 to 135.8±1.0 mmHg, p<0.01) and in nighttime (from 131.5±1.9 to 118.8±1.9 mmHg, p<0.001). Diastolic BP also decreased: in 24 hrs. (from 91.7±1.8 to 78.7±1.6 mmHg, p<0.05), in daytime (from 94.3±1.3 to 85.0±1.2 mmHg, p<0.05) and in nighttime (from 83.5±2.0 to 71.2±1.7 mmHg, p<0.01). Daily variability of BP, time index of BP and morning BP rise (from 37.6±2.0 to 23.9±1.9 mmHg, p<0.001) reduced. Normalization of daily profile of BP was observed in the majority of patients after 12 weeks of Lozap Plus therapy. Treatment resulted in reduction of number of patients with myocardial hypertrophy (from 50% to 30%, p<0.01), and of patients with diastolic dysfunction of left ventricle (from 43.3% to 30%, p<0.05). Therapy with Lozap Plus during 12 weeks was followed by decrease in MA from 56.7±1.1 mg/l to 9.0±0.5 mg/l. Lozap Plus demonstrated metabolic safety by assessing carbohydrate, lipid, nitric and electrolyte blood parameters. Increase in quality of life was observed by week 12 of treatment. Conclusion: Lozap Plus is efficient antihypertensive drug providing cardio- and nephroprotection, which doesn’t cause metabolic disturbances and improves quality of life of hypertensive patients.

27-30 514

Aim.  To assess antihypertensive efficacy of rilmenidine (Albarel, EGIS, Hungary) and its effect on cognitive function in elderly hypertensive patients. Material and methods. 30 elderly (in average 68 y.o.) hypertensive patients were observed. Each patient received therapy with rilmenidine 2 mg daily during 6 months. 24 hours monitoring of blood pressure before and after therapy was done in each patient. In order to assess cognitive disorders all patients passed neuropsychological tests, which allowed revealing damages of memory, attention, concentration, mental efficiency and psychomotor functions. Raten tests, Veksler test, vocal activity, memory (10 words), serial counting and kinetic probes were used. Results. After 24 weeks of monotherapy with rilmenidine, decrease in daily average systolic blood pressure (SBP) by 7.2% (p<0.01) and diastolic blood pressure (DBP) by 5.5% (p<0.05) was observed. Therapy with rilmenidine showed decrease in daily average burden by SBP and by DBP (by 25.3% and 18.8% respectively; p<0.05) and daily average time index of hypertension for SBP and DBP (by 32.5 and 60.6% respectively; p<0.05) According to the results of neuropsychological tests at the end of treatment, average time for Raten test completion decreased by 16.7% (p<0.05), and for Veksler test completion – by 15.6% (p<0.05). At the same time significant increase in vocal activity of patients is noted: number of words at free associations tests, verbs and plants denomination have grown by 5.8%, 5.1% and 6.3% respectively (p<0.05); number of mistakes in these tests decreased respectively by 71.4%, 50% and 33.3% (p<0.05). Positive dynamics in characteristics of memory: number of words at first and last immediate and postponed reproduction increased respectively by 36.4%, 21.6% and 14.1% (p<0.05),  average time of serial counting and average time of memorization decreased respectively by 13.2% and 31.8% (p<0.05). Velocity in both hands increased, which was observed both in tests on grip and fingering, and on reciprocal coordination. Conclusion. Well-defined antihypertensive effect of rilmenidine in elderly AH patients is accompanied by significant improvement of cognitive functions. This greatly expands opportunities of treatment with rilmenidine in this age group.

31-36 483

Aim. To reveal of markers of inflammation and progression of calcification in patients with degenerative aortic stenosis (DAS). Material and methods. A single-stage study was done in 85 patients with degenerative calcification of aortic valve (42 patients with DAS and 43 patients without DAS). The techniques for assessing the severity of aortic valve calcification included ultrasonic diagnostics and multislice spiral computed tomography. Markers of inflammation and lipid profile were investigated.    Results. Higher blood levels of total holesterol and holesterol of low density lipoprotein were revealed in patients with DAS in comparison with patients without DAS. They also had higher levels of inflammation markers: C-reactive protein and interleukin-6. There were significant correlations between DAS severity, lipid metabolism disturbances and inflammation markers. Conclusion. Atherogenesis and inflammation may have pathogenic influence on progression of aortic valve calcification and DAS development by lipid infiltration and endothelium cells damage.

37-40 240

Aim. To study efficiency and safety of propafenone internally used for recovery and support of sinus rhythm in patients with the persistent form of auricular fibrillation (AF). Material and methods. 503 patients with the persistent form of AF, aged 31-68 years were included into multicenter study. Patients were randomized into 2 groups. First group included 285 patients, who were prescribed propafenone (Propanorm, PRO.MED.CS Praha a.s., Czech Republic) in a single per oral dose of 600 mg for AF paroxysm relief. Second group included 218 patients, who took propafenone for AF paroxysm prevention in daily dose of 450 mg. Efficiency of sustaining antiarrhythmic therapy was assessed in 1, 3 and 9 months after the treatment started by carrying out daily monitoring of EKG. Results. Propafenone in a single per oral dose of 600 mg leaded to sinus rhythm recovery in 230 (81%) patients. Average time for sinus rhythm recovery made up 210±50 minutes. Relief, caused by propafenone within 4 hours after taking the drug, was observed in 182 (64%) patients. Propafenone in dose of 450 mg daily lets keep sinus rhythm after 1 month of treatment in 161 patients (74%), after 3 months – in 130 patients (60%) and after 9 months – in 98 patients (45%). Effect of preventive antiarythmic therapy within first 3 months of treatment with propafenone can be regarded good, and within 9 months – satisfactory. Conclusion. Propafenone in per oral single dose of 600 mg is an efficient method of sinus rhythm recovery in patients with the persistent form of AF, and its long-term usage in dose 450 mg daily is an efficient and safe method of sinus rhythm support.

41-47 367

Aim. To evaluate antiarhythmic efficiency of Nibentan (Verofarm, Russia), antiarrythmic drug III class, in supraventricular rhythm disturbances (SRD) relief in patients with ischemic heart disease (IHD). To assess morphological changes of myocardium in IHD with SRD. To specify inotropic characteristics of nibentan in experiment. Material and methods. 55 patients with IHD with different SRD were studied. 41 patients had heart failure (HF) of III functional class.14 other patients suffered acute myocardial infarction (AMI). SRD relief was achieved with 1% solution of nibentan in dose of 0.125 mg/kg patient's weight. After sinus rhythm recovery all patients received sotalol 80 mg twice a day to prevent SRD relapses. In vitro on myocardium of 10 healthy rats and 10 sliced myocardium strips of IHD patients (obtained during surgical intervention) changes in myocardium contraction intensity were assessed with PowerLab plant (ADInstruments, Australia) as a reaction on nibentan in doses of 4, 6 and 8 mkM. These doses correspond to doses of 0.125, 0.2 and 0.250 mg/kg, which are recommended for clinical practice. Histological study of autopsy materials of atrium myocardium of IHD patients with and without SRD was carried out. Phase-contrast and luminescent microscopy was also used. Results. Nibentan treatment lead to sinus rhythm recovery in 92.67% of HF patients. In 3 patients with persistent auricular fibrillation the drug was inefficient. Nibentan therapy did not result in blood pressure reduction. Heart rate decreased in 26.5%. Nibentan recovered sinus rhythm in 85.7% of AMI patients. Sinus rhythm didn't recover in 2 patients with persistent auricular fibrillation. Experimental studies revealed that myocardium contraction intensity in healthy rats increased at nibentan 4 and 6 mkM, and decreased at nibentan 8 mkM. Myocardium contraction intensity in IHD patients was decreasing while nibentan dose was growing. Histological study of auricular myocardium in IHD patients with SRD compared to myocardium in IHD patients without SRD, showed predominance of the following characteristics: fibrolipomatosis, focal and diffusive fibrosis and sclerosis, chaotic allocation of cardiac cells, muscular-elastic hyperplasia of vascular intima, contractile degeneration (at phase-contrast microscopy). Conclusion. Nibentan in bolus i.v. administration in dose of 0.125 mg/kg is effective drug for SRD relief in patients with IHD with HF and in patients with AMI. It doesn't affect BP significantly. According to data of experiments dose of nibentan 0.125mg/kg is optimal for inotropic function of myocardium. More significant histological changes in auricular myocardium can be the reason of SRD.

49-54 305

Publication is devoted to the calcium antagonist nifedipine in drug formulations of the prolonged action. Comparison of technological peculiarities of these formulations is given, pharmacokinetic and pharmacodynamic effects are reviewed. Data about therapeutic effects of nifedipine in different forms of the prolonged action at arterial hypertension and stable angina are observed. Questions of treatment safety are discussed. Conclusion about advantages of nifedipine in the formulation of gastrointestinal therapeutic system (GITS) is made.

55-58 302

Aim. To evaluate antihypertensive efficacy of nifedipine (N) and nifedipine complex (NC) in acute test in rats with adrenaline model of arterial hypertension. Material and methods. N is a conventional short acting formulation while NC is a new formulation of nifedipine in complex with glycyrrhizic acid. NC has an active substance 10 times less than N does in the same dose. Adrenaline which results in two times increase in blood pressure (BP) during 4 min was administered as a single i.v. dose (0,03 mg/kg) to normotensive unconscious male rats (body weight 190-220 g). NC and N were administered in the same dose (3,5 mg/kg) before and after adrenaline administration. Systolic BP recovering time was assessed. BP level was measured with direct method in carotid artery. Results. NC and N decreased in systolic BP in normotensive rats by 26 and 30% respectively. NC and N administered before adrenaline administration resulted in systolic BP recovering time reduction to 94,4 and 79,7 s respectively, which are less than this in control (204,8 s, р<0,001). Difference in time between NC and N is not significant (p<0,1). NC and N administered after adrenaline administration resulted in systolic BP recovering time reduction to 104,7 and 139 s respectively, which are also less than this in control (204,8 s, р<0,001). Difference in time between NC and N in this model is also not significant (p<0,1).  Conclusion. NC with contents of active substance 10 times less than in N showed antihypertensive efficacy similar with this in N. NC can be used for prevention and therapy of acute arterial hypertension.


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The proofs of necessity of active arterial hypertension (AH) treatment in elderly patients are given. Peculiarities of pathogenesis of AH in elderly patients, connected predominantly with loss of big arteries elasticity and reasoning widely spread of isolated systolic AH in these patients, are discussed. Advantages of dihydropyridine calcium antagonists (DPCA) for AH treatment in elderly patients are proved, safety of treatment with DPCA is discussed. Data of clinical studies is analyzed. Analysis of target levels of blood pressure for antihypertensive treatment in elderly hypertensive patients is made. As a conclusion DPCA are the medicines of choice for AH treatment in elderly patients.


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ISSN 2225-3653 (Online)