Rational Pharmacotherapy in Cardiology

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Vol 7, No 4 (2011)
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409-425 438

Aim. To estimate influence of thrombosis associated genetic factors on cardiovascular complications (CVC) occurrence in patients with stable ischemic heart disease (IHD) on the base of 5-year prospective survey. Material and methods. A total of 503 patients with the mean age of 59.4 years were enrolled into the study. The follow-up period was 5.4 years. Composite endpoint included the following cases of fatal and nonfatal CVC: death, acute coronary syndrome, ischemic stroke/transient ischemic attack, peripheral arterial thrombosis and revascularization of affected vascular system. We determined prevalence and prognostic value of mutations and polymorphisms in genes that encode blood clotting factors (factor V Leiden G1691A, prothrombin G20210A, ß-fibrinogen 455G> A), platelet GPIIIa receptor (C1565T) and enzymes involved in homocysteine metabolism (methylentetrahydrofolate reductase  (C667 T MTHFR) and A1298C, methionine synthase (MTR) A2756G, methionine synthase-reductase (MTRR) A66G and transcobalamin (TCN) C776G). Results. Overall incidence rate of vascular events made up 31.0%. MTHFR and TCN polymorphisms proved to be significant in regard to cardiovascular risk among all studied genetic indices. Carriage of at least C667 T one MTHFR polymorphic allele increased risk of CVC 1.64 times (95% confidence interval (CI) 1.2-2.3, p=0.003). Homozygous carriage of MTHFR 1298 AА and TCN 776 СС “wild” genotypes increased risk of CVC 1.63 times (95% CI 1.2-2.3, р=0.006) and 1.37 times (95% CI 1.001-1.89, р=0.04), respectively. Such genetic variants as MTHFR C667 T/СТ and 1298 AА impacted prognosis only given concomitant decrease in plasma folate level, which was observed in 56.1% of the patients. Conclusion. It can be recommended to test the presence of MTHFR C667 T, MTHFR 1298 AА and TCN 776 СС, and to simultaneously assess folate level in IHD patients in order to clarify risk of unfavorable cardiovascular events.

426-430 485

Aim. To evaluate efficacy and safety of treatment with fixed combination of ramipril and hydrochlorothiazide in patients with arterial hypertension (HT) 2-3 degree and high or very high cardiovascular risk in clinical practice. Material and methods. Patients with HT 2-3 degree and high or very high cardiovascular risk who had not reached target blood pressure (BP) levels with previous therapy (n=427) were included in open-label non-comparative multicenter phase IV study. Patients were treated with fixed combination of ramipril and hydrochlorothiazide during 8 weeks. The drug dose was increased and/or amlodipine was added in case of insufficient antihypertensive effect. Achievement of the target BP level (<130/80 mmHg) and therapy safety were assessed. Results. 420 patients (98.4%) completed the study. After 8 weeks 273 (65%) patients had a two-component therapy (fixed combination of ramipril and hydrochlorothiazide), 147 (35%) patients — triple therapy (ramipril, hydrochlorothiazide and amlodipine). The target BP level was achieved in 408 (97.14%) patients and it was not reached in 12 (2.86%) patients. 7 patients were dropped out from the study: 4 — because of adverse events (dry cough), 3 — due to violation of study protocol. Both patients and doctors considered fixed ramipril and hydrochlorothiazide combination as effective and well tolerable one.  Conclusion. Ramipril and hydrochlorothiazide fixed combination provides an achievement of the target BP level in the most of HT patients.

431-436 715

Aim. To study the therapeutic equivalence of original and generic fosinopril in patients with arterial hypertension (HT) of 1-2 degrees, and to evaluate the cost effectiveness of original drug substitution with generic. Material and methods. Patients (n=36) with HT of 1-2 degree aged 41-82 years and disease duration up 3 to 22 years included in an open, crossover , randomized trial. All patients had two courses of treatment: with generic (Fosicard) and the original drug (Monopril); sequence of courses was determined by randomization. Wash-out period (10-14 days) preceded each course. Treatment duration was 6 weeks; drugs were administered QD; initial dose - 10 mg/day. Blood pressure (BP) and heart rate (HR) were evaluated at the end of the wash-out period, and in 2, 4 and 6 weeks of therapy. In case of ineffective BP control (>140/90 mm Hg) hydrochlorothiazide 12.5 mg was added initially and dose fosinopril was increased up to 20 mg/day next. Results. Patients in groups were comparable by basic clinical parameters. Both fosinopril based drugs have comparable antihypertensive effect. Differences between their effect on systolic and diastolic BP as well as HR at all steps of treatment were not significant. The individual analysis revealed a tendency to more pronounced Monopril antihypertensive effect compared with Fosicard, but the differences were not significant. An average dose of Monopril was 11.8±3.9 mg/day , and Fosicard — 13.2±4.7 mg/day (p=0.13); the rate of monotherapy with both drugs of fosinopril at dose of 10 mg/day was similar (in 41% and 44% of patients, respectively); the rate of combined therapies with various composition differed insignificantly. Reduction in BP <140/90 mmHg was recorded at the end of the study in 29 (85.3%) patients treated with Monorpil and in 27 (79.4%) — Fosicard (p=0.52). Both drugs showed a good safety profile. Conclusion. Fosicard or its combination with hydrochlorothiazide is therapeutically equivalent to original drug (Monopril) or its combination with hydrochlorothiazide.

437-441 417

Aim. To study state of vascular wall within different levels of vascular bed in patients with arterial hypertension (HT) and ischemic heart disease (IHD), and the possibility of the correction of revealed disorders with antiplatelet agent — clopidogrel 75 mg/day. Material and methods. 40 patients with HT of 1-2 degree and IHD (stable angina of I-II functional class) were included into the study. 20 healthy volunteers were included into the control group. Pulse wave velocity (PWV) was evaluated by volumetric sphygmography. Microvasculature (MC) was evaluated by computerized ultrasound Doppler velocimetry. Plasma activity of von Willebrand factor (vWF) was evaluated by direct quantitative enzyme-linked immunosorbent chemical analysis. Results. Patients with HT and IHD have abnormalities of all levels of the vascular bed compared with subjects of control group: endothelial function (increased vWF), MC disorders (lack of the linear flow velocity augmentation 1.4% vs 23.7%), as well as increase in PWV in elastic type vessels (13.27±0.53 vs 8.37±0.76 m/s). Strong positive correlation (r=0.71; p<0.05) between HT duration and average linear velocity of blood flow was detected. Disease duration had direct correlation with MC disorders and PWV. There is correlation between MC changes and PWV in elastic vessels. Increase in vWF (168.7±9.1%) was detected in 28 (70%) patients of the main group. Blood flow velocity augmentation >20% during the test was observed in 27 (67.5%) patients treated with clopidogrel. Conclusion. Clopidogrel has effects on MC disorders and significantly reduces the vWF activity level.

442-446 390

Aim. To study the relations of clinical characteristics and individual warfarin dose titration in patients with atrial fibrillation. Material and methods. Period of warfarin dose titration was analyzed in 68 patients with atrial fibrillation due to ischemic heart disease. Adjusted warfarin dose in milligram, duration of dose titration in days and maximal international normalized ratio (INR) were taken into account. Sex, age, history of myocardial infarction and stroke, concomitant diseases, amiodarone therapy were considered among clinical characteristics. Results. Adjusted warfarin dose was significantly higher in obesity , and it was lower in case of experienced myocardial infarction. The INR highest levels and maximal amplitudes of its fluctuations were observed in patients with thyroid gland nodes and smokers. Period of warfarin dose titration was longer in patients treated with amiodarone. Conclusion. Warfarin dose titration in patients with atrial fibrillation depends on the presence of myocardial infarction, obesity , thyroid nodular changes, smoking and amiodarone treatment.

447-451 313

Background. Prolong contact with manufacturing factors of gas producing, in particular hydrogen sulfide, results in dysfunction of various organs and systems, including immune system, which is involved in regulation of the aging process activity. Absence of effective geropreventive means creates the need for pathogenetic way for aging process deceleration. Aim. To study the geroprotective properties of rosuvastatin in respect of people engaged in the gas producing. Material and Methods. The male workers (n=100) of the company “Gazprom dobycha Astrakhan” were examined. Evaluation of biological age by the method of Chebotarev D.F ., determination of p53 protein and interleukin-8, 10, 18 concentrations by solid phase enzyme immunoassay were performed before treatment start and after 18 months of rosuvastatin taking. Results. Rosuvastatin therapy in dose of 5 mg/day resulted in the reduction in atherogenic lipids, pro-inflammatory cytokine - interleukin-8 and marker of apoptosis - protein p53 as well as aging rate slowdown. Conclusion. Pathogenic method of geroprevention with rosuvastatin 5 mg/day was proposed for people engaged in gas producing.

452-456 369


Aim. To study of efficacy and safety of glycoprotein IIb/IIIa blocker monafram in acute ST-segment elevation myocardial infarction (STEMI) patients, underwent coronary stenting. Material and methods. 220 STEMI patients were included in the trial; they were split into two groups. 109 patients of the first group were underwent coronary stenting with i/v monafram therapy. Coronary stenting without monafram therapy was performed in 111 patients of the second group. Bare metal stents were used in all patients. Deaths, stent thrombosis, individual intolerance, allergic reactions, bleeding were registered during hospitalization. Results. There were 3 (2.75%) cases of stent thrombosis in monafram group and 4 (3.6%) ones - in the control group. Good tolerance of monafram was observed in all patients. There were no allergic reactions, major and minor bleedings. Reinfarction rate was similar in both groups during 30 days observational period. Conclusions. Monafram therapy is effective and safe in acute STEMI patients underwent coronary stenting.



457-462 435

Aim. To assess effect of ferrotherapy on course of ischemic heart disease (IHD) associated with mild iron deficiency anemia (IDA) and latent iron deficiency (ID). Material and methods. 80 male patients, coal miners, aged 51±7.9 years, were observed. 28 patients had angina pectoris associated with the mild IDA, 23 patients experienced myocardial infarction accompanied by the mild IDA and 29 patients had angina with latent ID. Latent ID was defined in case of iron plasma level ≤12 µg/l, IDA was diagnosed in case of hemoglobin level <130 mg/l. The minimal hemoglobin level observed in patients was 107g/l. ICD clinical characteristics were compared before and after 3-week iron-based treatment in individualized doses. Results. Latent ID and mild IDA aggravated angina and increased ectopic myocardial activity in patients with IHD. Iron-based therapy with appropriate nutrition reduced angina attacks frequency, duration and intensity, decreased nitroglycerin consumption and increased exercise tolerance. Conclusion. Normalization of haemoglobin level and iron plasma concentration in the mild IDA as well as normalization of iron plasma concentration in ID in patients with IHD reduces ede-ma and dyspnea, decreases heart rate. These effects are provided due to the treatment with elementary iron in individualized course dose, which improves clinical status and minimizes the adverse reactions.

463-467 325

Aim. To compare the efficacy of correction of modifiable risk factors for ischemic heart disease (IHD), and treatment compliance within 6 months of observation in group of men and group of women after acute coronary syndrome (ACS). Material and мethods. Patients (n=147: 100 men and 47 women) aged under 70 years who underwent ACS were examined. Prevalence of cardiovascular risk factors and frequency of basic drugs taking were evaluated at baseline and after 6 months. The efficacy of risk factors correction in men was compared with this in women. Results. A general number of patients with effective blood pressure (BP) control as well as patients who reached the target levels of total cholesterol (TC) <4.5 mmol/l and cholesterol of low>density lipoproteins (LDC) <2.5 mmol/l after 6 months increased significantly in comparison with this before observation. Taking of drugs from all main groups left unsatisfactory and did not>reach the advisable values. Women have better antihypertensive treatment compliance, but worse lipidemia level control; they more often have glucose metabolism disorders, arterial hypertension and obesity. Men smoked more often, but have better BP, TC and cholesterol LDC control. Conclusion. The high prevalence of cardiovascular risk factors requires intensification of preventive activity regarding IHD onset and progression among both men and women.


468-472 420

Pharmacotherapy optimization in patients with arterial hypertension and gout is very important. Achievement of the target blood pressure levels is possible with the use of combinations of effective antihypertensive drugs with neutral metabolic profile and safety, in particular a combination of valsartan, amlodipine and aliskiren. Clinical case of this combination use in patient with arterial hypertension and gout is presented.

473-476 340

Clinical case demonstrating the possibility of the left ventricle clot lysis due to combined anticoagulant therapy with warfarin and fraxiparine in patient with dilated cardiomyopathy, congestive heart failure and high risk of thromboembolic events is described.



477-482 4418

Peculiarities of the treatment with angiotensin II receptor blocker telmisartan are analyzed taking into account its clinical and pharmacological characteristics. Special attention is paid to the telmisartan benefits in comparison with other sartans. Key details of telmisartan interaction with peroxisome proliferator-activated receptors (PPAR) are discussed. Mode of this interaction distinguishes pharmacodynamic effects of different medicines. On the basis of presented data author concludes that antihypertensive therapy with telmisartan provides significant benefits.

483-486 384

Idiopathic mitral annular calcification (MAC) — pathological states that diagnosed mostly often by echocardiography in adult patients. It clinical importance is usually underestimated, in spite of available evidences of increased risk of unfavorable cardiovascular events in patients with MAC. The current understanding of MAC relation with other cardiovascular risk factors, ischemic heart disease and other atherosclerosis related diseases are reviewed. Besides, some clinical features and cardiac remodeling associated with MAC are discussed.



487-491 434

Magnesium deficiency in the organism is one of the most common human deficiency states. The prevalence of magnesium deficiency is about 15%, and suboptimal magnesium level is observed more than in 30% of people in the general population. Clinical signs of hypomagnesaemia are observed in 40% of patients in general care hospitals, in 70% of patients - in intensive care units, and magnesium deficiency occurs in 90% of patients with acute coronary syndrome. Magnesium metabolic disorders in the organism accelerate significantly development of complications of coronary heart disease, hypertension, type 2 diabetes, asthma and a number of neurological and psychiatric diseases. The value of this macro in the body is well studied, and its daily need is identified depending on age and sex. It is known that magnesium intake with the food does not cover an organism need. It is a rationale for preventive and therapeutic use of magnesium based drugs in various diseases. Organic salts of magnesium are recommended for these purposes. Magnesium metabolic disorders, approaches to pharmacotherapeutic correction of magnesium deficiency, advantages of magnesium salts of orotic acid are reviewed.

492-500 427

An experience of acetylsalicylic acid (ASA) clinical use since its synthesis in 1887 is highlighted. ASA modes of action and its position among the modern antiplatelet agents are considered. The evidence based clinical data on ASA treatment and the problem of antiplatelet therapy resistance are discussed. ASA interaction with other drugs and ASA pleiotropic effects are reviewed


501-506 817

Blood pressure (BP) control in patients with chronic kidney disease is one of the most pressing problems in modern cardiology and nephrology. Perindopril therapy reduces cardiovascular risk in patients with arterial hypertension and nephropathy, provides adequate BP control and target organs protection.



510-515 350

A review of international recommendations, including methods to assist in smoking cessation is presented. Particular attention is paid to the recommendations for treatment and prevention of cardiovascular disease. There are a lot of approaches to drop smoking including innovative pharmacotherapy. Implementation of these approaches is rational at all steps of health care for cardiovascular patients.


516-518 345

Key findings of STICH (Surgical Treatment for Ischemic Heart Failure) trial are presented. This study goal was to evaluate the role of the surgical intervention for coronary artery bypass grafting in improvement of life prognosis in patients with ischemic heart disease complicated severe heart failure.

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