[Specific Features of Pharmacotherapy of Patients With Chronic Heart Failure and Preserved Left Ventricular Ejection Fraction].

The review is devoted to pharmacotherapy of chronic heart failure (CHF) with preserved left ventricular ejection fraction. In this review we discuss data of meta-analyzes of randomized clinical trials and observational studies, as well as the indications for use of inhibitors of the renin-angiotensin-aldosterone system, ß-blockers, and antagonists of mineralocorticoid receptors in these patients in current clinical guidelines. New approaches to therapy of CHF from the perspective of influence on myocardial fibrosis are considered in this review.

[Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release].

Review oral modified release drug forms of beta-adrenoblocker metoprolol which is used in arterial hypertension and ischemic heart disease is presented. Metoprolol has salts such as tartrate which is used for production of immediate release (IR) and sustained release (SR) forms and succinate used for production of controlled release form (CR/XL). Metoprolol SR has monolith matrix type, metoprolol CR/XL-system of multiple pellets. Effect of metoprolol tartrate (IR) on mortality was demonstrated in a number of studies in patients with arterial hypertension (AH) (MAPHY), myocardial infarction (SMT, GMT, MIAMI), dilated cardiomyopathy and heart failure (MDC). Studies of efficacy of metoprolol SR are scarce. Antihypertensive efficacy of metoprolol SR in patients with AH did not exceed that of a metoprolol IR or CR/XL. First retrospective analysis of efficacy of metoprolol tartrate and succinate (CR/XL) in patients after myocardial infarction allowed to obtain comparable results of 34% mortality lowering. In a prospective study in patients with chronic heart failure (COMET) metoprolol tartrate IR was not superior to carvedilol when mortality lowering was concerned. At the same time administration of controlled release metoprolol (CR/XL) in 2 large clinical trials (RESOLVD, MERITAHF) was advantageous in patients with chronic heart failure relative to lowering of mortality and rate of hospitalizations. A novel controlled release form of metoprolol has been created as a tartrate salt on the basis of pellet technology (CD/ERT) and its bioequivalence to metoprolol CR/XL has been proved.

[Hypotensive, organoprotective, and metabolic effects of Angiotensin converting enzyme inhibitor moexipril in women with postmenopausal syndrome].

Hypotensive, organoprotective, and metabolic effects of angiotensin converting enzyme inhibitor moexipril (7.5-15 mg/day for 16 weeks) with or without combination with hydrochlorothiazide was studied in 34 women (mean age 59.6+/-1.6 years) with postmenopausal metabolic syndrome and hypertension. Thirty four women had dyslipidemia, 22 -- disturbances of carbohydrate metabolism, 18 -- obesity (mean body mass index 31.1+/-0.8 kg/m(2)). Treatment was associated with lowering of office systolic(-20.1%) and diastolic (-17.4%) blood pressure (BP). Target BP (140/90 mm Hg) was achieved in 27 patients. There also occurred significant lowering of mean 24 hour, diurnal, and nocturnal systolic and diastolic BP (p<0.05), significant changes of values of systolic and diastolic BP time indexes, normalization of which was observed both during day and night hours. Significant lowering of total cholesterol (-11.6%, p<0.05), low density lipoprotein cholesterol (-16.3%, p<0.02), and in patients with obesity of triglycerides (-27%, p<0.02) was revealed at the background of treatment with moexipril. In a group as a whole we observed significant lowering of excretion of albumins and b2-microglobulin; most pronounced antiproteinuretic effect was noted in patients with high microproteinuria and obesity. Vasodilating function of vessels improved in all patients with postmenopausal metabolic syndrome, mainly at the account of increment of endothelium dependent vasodilation and normalization of index of vasodilatation.

[Comparative efficacy and safety of contemporary Angiotensin converting enzyme inhibitors moexipril and spirapril in women with postmenopausal metabolic syndrome].

Moexipril (7.4-15 mg/day) was given to 34, spirapril (3-6 mg/day) -- to 18 postmenopausal women with hypertension and metabolic syndrome for 16 weeks. Hydrochlorthiazide was added when therapy was not sufficiently effective. Both angiotensin converting enzyme inhibitors had similar hypotensive activity: blood pressure normalized in 71 and 61% of moexipril and spirapril treated women, respectively. Both drugs promoted normalization of metabolism of lipid (lowering of levels of cholesterol, atherogenic lipoproteins and triglycerides) and carbohydrates (lowering of hyperinsulinemia). Patients with postmenopausal metabolic syndrome had elevation of leptin level up to 27.5+/-5.5 pg/ml. Moexipril and spirapril caused lowering of elevated levels of leptin. These drugs did not affect levels of sex hormones. They exerted vasoprotective (normalization of endothelium dependent and independent vasodilatation) and nephroprotective (attenuation and normalization of microalbuminuria) effects. Thus spirapril and moexipril are effective in treatment of hypertension in patients with postmenopausal metabolic syndrome.

[Results of pharmacoepidemiological study of arterial hypertension in Russia (PIFAGOR)]. / Rezul'taty farmakoépidemiologicheskogo issledovaniia arterial'noi gipertonii v Rossii (PIFAGOR).

AIM: To assess physicians preferences concerning the use of various groups of antihypertensive drugs in Russia. METHODS: Special questionnaires containing 8 questions related to preferential adherence to representatives of various groups of antihypertensive drugs were distributed among practicing physicians who routinely treated patients with hypertension. RESULTS: Of questionnaires returned between January and July of 2002 from 34 towns 530 were considered valid for analysis. Half of responses (50.4%) were from hospital physicians, 40.5% - from physicians of policlinics (outpatient clinics), 9.1% - from physicians working in other health care facilities. Most of respondents were internists (60.8%) and cardiologists (32.7%). Preferences concerning prescription of antihypertensive drugs were distributed in the following way: angiotensin converting enzyme inhibitors - 32% (50% captopril and enalapril); beta-adrenoblockers - 27% (77% atenolol, metoprolol and propranolol); diuretics (hydrochlorothiazide and indapamide) - 22%; calcium antagonists - 15% (81% verapamil, nifedipine, diltiazem, 64% - long acting preparations); angiotensin receptor blockers - 1.7%; centrally acting drugs - 1.5%; alpha-adrenoblockers - 0.8%. CONCLUSION: Tendencies in real life treatment of patients with hypertension in Russia should be considered positive. Basic antihypertensive therapy included agents (mostly long-acting) from 4 main classes and the use of outdated drugs such as clonidine and reserpine was low.

[Various aspects of the anti-aggregatory action of diltiazem and cordaphene in patients with ischemic heart disease]. / Nekotorye aspekty antiagregantnogo deistviia dilzema i kordafena u bol'nykh ishemicheskoi bolezn'iu serdtsa.

Some aspects of the antiaggregatory action of calcium antagonists were studied in 50 patients with stable angina pectoris. Dilzem (diltiazem) and cordaphene (nifedipine) were tested for their effects on the erythrocytic component of hemostasis, taking into account their capability of suppressing hemolysis, which made ADP, an important thrombocytic activator, enter the blood flow. The two agents significantly reduce the concentration of plasma ADP, free hemoglobin, diminish mechanical erythrocytic resistance, and block platelet aggregation to a varying degree. A relationship was established between the levels of blood nifedipine and the magnitude of rheological effects. With this, the patients with coronary heart disease showed a good antianginal effect.

[Selective microproteinuria as a marker of incipient renal impairment in patients with hypertension]. / Selektivnaia mikroproteinuriia kak marker nachal'nogo porazheniia pochek u bol'nykh s arterial'noi gipertenziei.

Incidence of chronic renal failure has a worldwide tendency to growth. Hypertension occupies an important place among causes of this upward trend. That is why in patients with hypertension and incipient changes of the kidneys it seems most appropriate to use antihypertensive drugs with renoprotective properties. Early treatment with these drugs enables most effective lowering of risk of renal failure development and thus has a potential to prolong life of a patient. Selective microproteinuria is considered to be a marker of incipient renal impairement. Among groups of antihypertensive agents angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium antagonists, beta-blockers, and diuretics have proven renoprotective properties.

[Effect of diltiazem on the functional activity of erythrocytes and thrombocytes in patients with ischemic heart disease]. / Vliianie diltiazema na funktsiona'lnuiu aktivnos't éritrotsitov i trombotsitov u bo'lnykh ishemicheskoi bolez'niu serdtsa.

The functional activity of erythrocytes and platelets was studied in 50 patients with various types of coronary heart disease. The patients' plasma exhibited higher ADP levels due to erythrocyte microhemolysis and higher platelet malonic dialdehyde and intracellular calcium, which led to enhanced platelet functional activity. Treating the patients with the calcium antagonist diltiazem was found to result in lower ADP and platelet calcium levels whereas the concentrations of malonic dialdehyde remained unchanged.

[The evaluation of cilazapril efficacy in patients with stable arterial hypertension (a randomized study)]. / Otsenka éffektivnosti tsilazaprila u bol'nykh stabil'noi arterial'noi gipertoniei (randomizirovannoe issledovanie).

34 patients with stable arterial hypertension (AH) were randomized by mean arterial pressure (MAP), end-diastolic LV volume and cardiac output in a study of cilazapril efficacy in a dose 2.5 and 5 mg/day. Antihypertensive effect in the majority of patients with MAP 120-135 and 136-150 mm Hg was insufficient (diastolic pressure > 94 mm Hg). Dose-effect action on hemodynamics was absent. Hemodynamic benefits were noted in patients with end diastolic LV volume > 5.0-5.7 cm.

[An analysis of the indices of ambulatory circadian blood pressure monitoring in patients with arterial hypertension]. / Analiz pokazatelei ambulatornogo sutochnogo monitorirovaniia arterial'nogo davleniia u bol'nykh arterial'noi gipertoniei.

The authors have found that more accurate prognosis of left ventricular myocardial hypertrophy (LVMH) may be made basing on fluctuations and variability of arterial pressure throughout the day: significant fluctuations of arterial pressure at night and pronounced variability of systolic arterial pressure in the day time and at night are indicative of essential hypertension instability and may contribute to LVMH progression. Of still greater prognostic significance is assessment of 24-h arterial pressure rhythm by the degree of a night fall (DNF) in diastolic arterial pressure (DAP). A disturbed 24-h rhythm of arterial pressure (a fall in DNF of DAP) is a predictor of LVMH development.

[The clinical efficacy of auricular electroacupuncture in treating hypertension patients]. / Klinicheskaia éffektivnost' élektroaurikuloakupunktury pri lechenii bol'nykh gipertonicheskoi bolezn'iu.

Auricular electroacupuncture using 10 Hz alternating impulse current generated by Rampa-2 apparatus has been employed to treat 98 patients with essential hypertension stage I-II. The treatment resulted in the fall of both systolic and diastolic pressure (p less than 0.01). The symptoms relieved in stage I hypertension by 66 +/- 2.4%, in patients with stage II by 57 +/- 1.1%, thus allowing discontinuation of the drugs in the former group and reduction of their intake in the latter one.

[The effect of auricular electroacupuncture on the initial manifestations of cerebral circulatory failure in hypertension patients]. / Vliianie élektroaurikuloakupunktury na nachal'nye proiavleniia nedostatochnosti mozgovogo krovoobrashcheniia u bol'nykh gipertonicheskoi bolezn'iu.

Hypertensive subjects with stage I-II of the disease received a course of differentiated electroauriculoacupuncture (EAAP) or auricular acupuncture (AAP). Though clinical findings and the trend in cerebral hemodynamics reflected positive results of both modalities, EAAP effect proved superior especially in essential hypertension stage II.

[The effect of acupuncture on endocrine regulation in hypertensive patients]. / Vliianie akupunktury na éndokrinnuiu reguliatsiiu u bol'nykh gipertonicheskoi bolezn'iu.

Thirty-five stage I-II essential hypertension subjects aged 25-63 were examined after the 1st and 10th acupuncture to clarify the effect of a single procedure and a course of acupuncture treatment on blood ACTH, STH, TTH, beta-endorphine, neurotensin, thyroxine, aldosterone, hydrocortisone and plasma renin activity. The hormonal spectrum was determined by radioimmunoassay using special kits. The blood was obtained before acupuncture, 5 min after introduction of the needles, immediately and 30 min after their removal. It is shown that acupuncture-related decline of arterial pressure occurs in participation of pituitary and adrenal hormones as well as polypeptides beta-endorphine and neurotensin.

[A pharmacoeconomical analysis of idiopathic epilepsy].

We have analyzed pharmacoeconomical indicators in the treatment of idiopathic (generalized and focal) epilepsy in children and adolescence in an ambulatory treatment/diagnostic center of a big industrial city. In the total structure, focal epilepsy made up 41.73% (255 patients, 128 boys (50.2%) and 128 girls (49.8%)). Generalized forms were diagnosed in 61.96% (n=158) and partial forms - in 37.6% (n=97%) patients. Minimal direct and indirect costs for one patient were calculated for patients in remission and did not depend on the form of epilepsy. The costs increased by a magnitude of two or more for treatment efficiency 50% and by 3 times for insufficient efficiency of treatment of different forms of epilepsy. In case of a loss of control of seizures, indirect costs exceeded the economy of direct costs. Adequate treatment of idiopathic epilepsy in children is economically profitable because it allows to improve quality of life of a child and maintain manpower resources in the nearest future.

[Epilepsy in adults: a costs-of-illness study].

An aim of the study was to assess clinical-economic effectiveness of therapy in the stages of examination of an epileptic patient by a local neurologist and then by an epileptologist after therapy optimization. Three hundreds and ten patients with different forms of epilepsy and types of epileptic seizures were treated. Costs-of-illness and medical services were assessed using common parameters on the basis of current prices in the health-care system. Special attention was drawn to expenses related to purchasing of antiepileptic drugs (traditional and new ones). The expenses for treatment were compared to treatment effectiveness. It is concluded that mean costs of treatment of epilepsy, including new brands of antiepileptic drugs with high prices, have substantial medical-social benefits that compensate expenses for their purchasing at the expense of other direct and indirect costs.