Rational Pharmacotherapy in Cardiology

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Vol 6, No 4 (2010)
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434-437 379

The organization of randomized clinical trials (RCTs) in accordance to the principles of Good Clinical Practice (GCP) is presented. The situation with RCTs in Russia and worldwide is also considered. Issues that must be addressed to improve a quality of the RCTs are reviewed. Information about Russian clinical and epidemiological studies structured for this purpose. The CONSORT (Consolidated Standards of Reporting Trials) Statement was designed to improve the quality of reporting the results of RCTs by group of scientists and editors. Publication of the translation of this important document starts in this issue of the journal.


438-446 442

Aim. To evaluate influence of various drug combinations on heart rate variability (HRV) in patients with previous Q-wave myocardial infarction (Q-MI) in outpatient period of rehabilitation.

Material and methods. A total of 316 patients with previous Q-MI were randomized into three groups. Patients of the control group (n=103) received standard therapy (acetylsalicylic acid, enalapril, metoprolol, simvastatin) during 2 years after discharge from the hospital. Patients of the first studied group (n=107) were additionally treated with trimetazidine, and patients of the second group (n=106) received combined therapy with ramipril, carvedilol and trimetazidine. HRV parameters (derived from ECG 5-minute recording) were registered at the beginning of the study, 6 and 24 months after the beginning of the study.

Results. HRV parameters improvement was more significant in the second group compared to the first and to control groups. In the second group LF increased from 223.8±56.2 to 734±90.9 мs2 (p<0.001), in the first group – from 217.8±54.3 to 713±88.1 мs2, and in control group – from 225.4±49.0 to 589±72.0 мs2. HF increase was also more significant in the second group: from 189.5±54.4 to 801±97.5 мs2 (p<0.001) compared to the first and to control groups: from 176.6±47.3 to 579±91.2 мs2 and from 180.9±50.4 to 487±83.4 мs2, respectively. SDNN rose from 27.8±3.2 to 52.4±4.4 ms (p<0.05) in the second group, from 27.4±2.7 to 41.2±3.8 ms in control group, and from 26.7±3.0 to 46.5±4.0 ms in the first group. RRNN increased from 664.5±99.0 to 833±98.7 ms (p<0.05) in the second group, from 676.2±85.3 to 793±87.6 ms in control group, and from 658.1±97.2 to 826±92.8 ms in the first group.

Conclusion. Two-year treatment with enalapril and metoprolol as a part of standard therapy improves HRV parameters of Q-MI patients. Addition of trimetazidine to this combination leads to even more significant improvement of HRV parameters in postinfarction period. The most significant effect on the reduction of sympathetic nervous system activity, increase in parasympathetic nervous system activity as well as improvement of HRV parameters was observed in therapy with combination of trimetazidine, ramipril and carvedilol.

447-454 320

Aim. The main aim of the present study was to evaluate quality of life changes and compliance to therapy in patients following successful transluminal angioplasty, who were prescribed fluvastatin extended release in addition to standard treatment.

Material and methods. This was a national prospective multicenter observational study. Patients with coronary heart disease following successful transluminal coronary angioplasty, who were prescribed fluvastatin extended release (Lescol Forte, Novartis) 80 mg QD were included in the present observation. The following efficacy and safety parameters were evaluated: quality of life evaluated with SF-36 scale before and during treatment; hypolipidemic efficacy, compliance to therapy; adverse events and serious adverse events. Observation period was 6 months in all patients and 12 months in some patients at the discretion of the investigator.

Results. 524 patients (79% men and 21% women) completed the 6 months observation period and 116 patients were followed up for 12 months. Significant increase of all measures of SF-36 scales, physical and mental health was observed in 6 and 12 months of fluvastatin extended release treatment. Total and low density lipoprotein cholesterol reduction was 30.5% and 54.9% respectively, p<0.01, in 6 months and 34.2% and 34.3% respectively in 12 months of treatment, p<0.01. High density lipoprotein cholesterol was significantly increased by 22.5% in 12 months of treatment, p<0.01. There were very few adverse events and laboratory changes during the course of treatment.

Conclusion. LESQOL study showed significant increase in quality of life and good hypolipidemic efficacy as well as good tolerability of fluvastatin extended release in patients after coronary angioplasty.

455-460 479

Aim. To evaluate antianginal efficacy and safety of nicorandil for angina attack prevention and relief in patients with ischemic heart disease (IHD) and symptoms of stable angina class 2-3.

Material and methods. 30 patients with stable angina class 2-3 (17 men, 13 women; aged 58.6±5.8 y.o.) were included into the study. All patients received amlodipine 10 mg QD within 2 weeks. For angina attack relief patients used nicorandil 10-20 mg and in case of its inefficacy — nitroglycerin. In 2 weeks all patients were randomized in 2 groups. Patients of the 1st group (n=15) received nicorandil 20 mg TID, patients of the 2nd group (n=15) — amlodipine 10 mg QD. The study duration was 3 months. The efficiency evaluation was based on the analysis of hemodynamic indicators (heart rate, blood pressure), bioelectric heart activity (electrocardiogram), velocity exercise tolerance test, ambulatory blood pressure monitoring indicators. The pain severity was defined with Borg's scale, and the quality of life — with General Health Questionnaire (GHQ-28). Therapy safety was evaluated in according to laboratory tests results.

Results. Frequency of angina attacks reduced by 60% (р<0.05) and 47% (р<0.05) in 12 weeks of nicorandil and amlodipine therapy, respectively. Duration of angina decreased by 38% and 37% (р<0.05) in 12 weeks of nicorandil and amlodipine therapy, respectively. Eexercise duration before angina attack onset increased by 56% (р<0.05) in 1 month of nicorandil therapy. A number of myocardial ischemia episodes reduced by 64% (р<0.05) and 54% (р<0.05) due to nicorandil and amlodipine therapy, respectively. General GHQ-28 score decreased by 54% (р<0.05) and 44% (р<0.05) in patients of the 1st and the 2nd groups, respectively. Tolerability of nicorandil was good in 13 (86.7%) and satisfactory in 2 (13.3%) patients.

Conclusion. Nicorandil can be prescribed both for the prevention and for relief of angina attacks in IHD patients.

461-468 414

Aim. To study relationship of the clinical state and cardiac functional parameters with magnesium metabolism indices in patients with chronic ischemic heart disease (IHD).

Material and methods. Patients with stable angina pectoris, II-III class (n=480) were involved into the study. Evaluation of the following items was performed: disease course, anxiodepressive syndrome intensity, exercise tolerance, blood and urine electrolyte profile, systolic and diastolic left ventricle function, endothelium-dependent and endotheliumnondependent vasodilatation, i/v magnesium load test, Holter electrocardiogram monitoring.

Results. High prevalence of systemic magnesium deficiency (17.9 and 37.5% according to serum and erythrocyte levels, respectively) was found in IHD patients. Severity of magnesium deficiency in IHD patients depended on duration of disease, experience of myocardial infarction, myocardial ischemia seriousness, disorders of endothelium vasodilating function and left ventricle diastolic function, severity of concomitant anxiety. Exercise tests were changed in IHD patients with magnesium deficiency.

Conclusion. The study data let to consider that magnesium deficiency involves into the IHD pathogenesis.

469-473 368

Aim. To estimate economic efficiency of a complex of resource-saving activities for cardiovascular diseases prevention at a workplace.

Material and methods. The complex of activities including preventive examination and preventive intervention with their efficacy monitoring was performed in 523 people of a technical research institute staff. Preventive examination included evaluation procedures for cardiovascular diseases and their risk factors (89,5% of respondents). Preventive intervention based on risk factors modification was performed in intervention group. Control group included staff not participating in preventive consultation. Costs associated with cardiovascular diseases and risk factors (medical care consumption and temporary disability) and cost- efficiency analysis was performed.

Results. High prevalence of arterial hypertension, metabolic and psychoemotional risk factors at workplace was found in preventive examination. Significant reduction in blood pressure (BP) and total cholesterol (TC) plasma level as well as a tendency to cardiovascular risk (CVR) decrease was reached due to preventive intervention. Costs associated with cardiovascular diseases and their risk factors in intervention group were lower than these in control group (168 584 and 489 500 rbl per 100 people yearly, respectively). Cost- efficiency analysis shown that costs of BP, TC plasma level and CVR reduction were moderate in intervention group. Costs were not efficient in control group.

Conclusion. Implementation of cardiovascular diseases prevention at workplace is economically efficient both for society and for employer.

474-480 660

Background. Atherosclerosis is a systemic disease. That is why the damage is not restricted by one vascular area in 18-50% of patients. High serum level of lipoprotein(a) [Lp(a)] is an independent risk factor for coronary, carotid and peripheral atherosclerosis. However the correlation of apoprotein(a) [apo(a)] polymorphism with the multifocal atherosclerosis in coronary heart disease (CHD) is not sufficiently studied.

Aim. To study the correlation of apo(a) phenotype with the multifocal atherosclerosis in CHD patients.

Material and Methods. 220 patients aged 32- 76 y.o. with the proven coronary and carotid atherosclerosis were split into two groups depending on the presence (n=22) or absence (n=198) of peripheral atherosclerosis. Evaluation of lipid profile, Lp(a) and determination of apo(a) isoforms by SDS electrophoresis in polyacrylamide gel and immunoblotting was performed in all patients.

Results. Both groups of patients were comparable by age, sex, classical cardiovascular risk factors, including frequency of hyperlipidemia and diabetes mellitus, lipid profile. The Lp(a) serum level ≥30 mg/dL and low molecular weight (LMW) apo(a) phenotype were found more often in patients with multifocal than coronary and carotid atherosclerosis: 55 and 45% (р=0.372); 73 and 44% (p<0.05), respectively. According to multiple regression analysis (including sex, age, smoking status, and Lp(a) serum level) only smoking status (β=0.203, p=0.0003) and a size of apo(a) isoforms (β=0.191, p=0.0133) correlated with the peripheral atherosclerosis in patients with CHD. LMW apo(a) phenotype was the most significant predictor of peripheral atherosclerosis (β=0.281, p=0.0089) regardless of the Lp(a) serum level in patients under 55 y.o. High Lp(a) serum level combined with LMW apo(a) phenotype associated with more significant coronary, carotid and peripheral atherosclerosis.

Conclusion. LMW apo(a) phenotype relates to the presence of multifocal atherosclerosis in CHD patients regardless of the Lp(a) serum level. Apo(a) phenotype can be a marker of generalized atherosclerosis especially among young adults. Next studies of correlations Lp(a) and apo(a) phenotype with lower limb arteries lesions are needed in various patients.

481-484 473

Aim. To find the optimal scheme of lycopene application and to compare clinical efficacy of two lycopene presentations produced on the basis of 1) vegetable oil and 2) milk protein (lactolycopene) in patients with dyslipidemia.

Material and methods. At the first step of the study to choice an optimal scheme of pharmacotherapy efficacy of three schemes of lycopene (lactolycopene) application was compared in three groups of patients (n= 27, 25 and 28 respectively) with ischemic heart disease, dyslipidemia and high level of lipid peroxygenation (LPO). At the second step two groups of patients (n=28 and 31) with dyslipidemia received lycopene in the same dose at the same time but in different presentations. Patients of the first group received oil solution of lycopene in capsules, patients of the second group — a powder of lactolycopene dissolved in 100 ml of boiled water. Levels of total cholesterol (TC), high density (HDC) and low density cholesterol (LDC), triglycerides (TG) and LPO activity marker, malondialdehyde (MDA), were studied. The duration of each study step was 8 weeks.

Results. Lactolycopene 10 mg QD for the night was as effective as 10 mg TID (30 mg per day) in normalization of the lipid metabolism parameters and malondialdehyde level due to chronopharmacological mechanism. Similar efficacy of the evening lactolycopene reception 10 mg QD and 30 mg QD was due to the saturation of tissues with an antioxidant. Lactolycopene application led to significant reduction in levels of TC (from 247.1±27 to 186.5±12 mg/dl; p<0.001), LDC (from 150.9±17 to 119.3±8 mg/dl; p<0.001), TG (from 165.8±12 to 128±10 mg/dl; p<0.001) and MDA (from 2.67±0.2 to 1.3±0.07 nM/ml; p<0.001) unlike reception of oil solution of lycopene.

Conclusion: Lactolycopene has higher effect on lipid metabolism and LPO in comparison with this in lycopene in oil solution presentation. An optimal scheme of lactolycopene reception is 10 mg for the night.

485-490 434

Aim. To perform cost-effectiveness analysis of 24 weeks antihypertensive therapy based on carvedilol or metoprolol in patients with arterial hypertension (HT) 1-2 degrees and overweight/obesity. To assess effects of carvedilol therapy on 10-year expected risk of cardiovascular complications (CVC).

Material and methods. Patients with HT and overweight/obesity (n=320) were included into the study and randomly split in two groups. Patients of the first group (n=160) received carvedilol as a basic therapy and patients of the second group (n=160) — metoprolol. Both groups of the patients were comparable on key clinical characteristics.

Results. In 24 weeks of treatment systolic and diastolic blood pressure (BP) decreased significantly in comparison with the baseline level (p<0.0001). Dose doubling of beta-blockers was required more often in patients treated with carvedilol. At the same time a combined antihypertensive therapy of the patients treated with carvedilol was required less (p>0.05). Target BP levels were achieved in carvedilol and metoprolol groups in 96.2and 95.5% of patients respectively (p=0.85). Carvedilol had better effect on plasma metabolic indicators such as glucose (p<0.01), lipid profile, uric acid level. Reduction in expected 10-year risk of death was more pronounced in 24 weeks carvedilol treatment. Cost of target BP level achievement was approximately 2.5 times higher in carvedilol group than this in metoprolol group. However cost of additional therapy was higher in metoprolol group. 1% reduction of the 10-year expected risk of CVC death cost 1 847 rubles in carvedilol therapy.

Conclusion. Carvedilol therapy (vs metoprolol one) has a higher cost under comparable efficacy. Additional expenses are compensated with the favorable effect on metabolic indices and a more pronounced effect on reduction in the 10-year expected risk of CCO death. That is why carvedilol can be recommended to patients with HT and metabolic risk factors. Longer studies are necessary to assess an effect of carvedilol therapy on prognosis in patients with HT and concomitant metabolic disorders.

491-496 449

Aim. To study the antihypertensive and metabolic effects of lisinopril plus amlodipine combination in hypertensive men with high cardiovascular risk.

Materials and methods. Hypertensive men (n=21) with high cardiovascular risk (SCORE scale >5%) aged 30-59 y.o. were included in the study. Questionnaire survey, blood pressure (BP) and heart rate measuring, anthropometric studies, evaluation of the plasma lipid profile, uric acid level and glucose tolerance test were performed at baseline and at the end of the study. Erectile function was assessed by International index of erectile function (IIEF) score. After the cancellation of previous antihypertensive drugs patients were prescribed lisinopril 10 mg QD and amlodipine 5 mg QD. The duration of the study was 6 months.

Results. In 4 weeks of the treatment systolic and diastolic BP decreased by 9.3 and 5.2%, and in 24 weeks – by 14.7 and 7.2% respectively (p<0.05). Target BP levels were achieved in 85% of patients. Antihypertensive therapy during 6 months had no significant effect on the plasma lipid profile, glucose and uric acid levels. The mild to moderate-mild erectile dysfunction were detected in 35% of men before therapy. Erectile function indices in hypertensive men with high cardiovascular risk had not changed during combined antihypertensive therapy.

Conclusion. Antihypertensive therapy with lisinopril and amlodipine in hypertensive men with high cardiovascular risk during 6 months led to a statistically significant reduction of BP level without affect plasma lipid profile, glucose and uric acid levels as well as erectile function.

497-501 1067

Aim. To compare clinical efficacy and effect on endothelium function of original bisoprolol and its generic in patients with stable angina and concomitant chronic obstructive pulmonary disease (COPD).

Material and methods. Patients with the stable angina and COPD (n=72) were included into the study. Patients were randomized for treatment with the original bisoprolol (1st group; n=36) and the generic bisoprolol (2nd group; n=36). Endothelium-dependent vasodilation test, office measurement of heart rate in 2 hours after bisoprolol taking, 24-hour electrocardiogram-monitoring, evaluation of respiratory function, level of nitrogen oxide metabolites were are performed initially and in 12 weeks.

Results. Antihypertensive and antiischemic effects were observed in both groups in 12 weeks of treatment. However significant improvements of endothelial function were detected only in patients of the 1st group. Heart rate reduction from 98.6±2.5 to 58.6±3.5 bt/min (р<0.001) was found with the 24 hour electrocardiogram-monitoring after 12 weeks of therapy in the 1st group and from 96.9±4.9 to 66.3±5.6 bt/min (р<0.001) in the 2nd group. Reached heart rate level in the 1st group was less than this in the 2nd group (р<0.001). Negative changes of respiratory function were absent in the both groups in 4 weeks of treatment, however significant reduction of respiratory indices was registered in the 2nd group after 12 weeks of treatment.

Conclusion. Original bisoprolol is more effective and tolerable than generic bisoprolol in patients with the stable angina and concomitant COPD.

502-507 490

Aim. To evaluate influence of the combined therapy with ACE inhibitor (perindopril), diuretic (indapamide) and dihydropyridine calcium channel blocker (amlodipine) on ambulatory blood pressure (BP) monitoring indices and heart rate variability in hypertensive patients during early recovery period of stroke.

Material and methods. 39 patients (28 men, 11 women) with arterial hypertension of 1-3 degrees during early recovery period after stroke were examined. They received perindopril 10 mg QD, indapamide — 1.5 mg QD. Calcium channel blocker amlodipine (5 mg QD) was added in case of insufficient effect of the ACE inhibitor plus diuretic combination.

Results. The combined antihypertensive therapy in hypertensive patients after the stroke led to significant decrease of systolic and diastolic BP (by 23.5% and 18.9%, respectively), normalization of BP daily profile (a number of «dippers» enlarged by 42.2%), improvement of the wall vessel rigidity (decrease in pulse wave velocity by 12.9%) and heart rhythm variability (increase in SDNN, PNN50 and RMSSD by 7%, 20% and 25%, respectively).

Conclusion. Advantages of the combined antihypertensive therapy (ACE inhibitor, diuretic, calcium channel blocker) in treatment of hypertensive patients after the stroke are shown.

508-512 348

Aim. To investigate effects of acute physical exercise of varying intensity on lipid metabolism in middle aged men.

Material and methods. Two bouts of physical exercise of moderate and high intensity were performed in 54 clinically healthy men aged 30-45 y.o. without obesity with subsequent assessment of lipid profile (total cholesterol, high density lipoprotein cholesterol, triglyceride levels, and atherogenic index). Effect of physical exercise on the lipid profile as studied both in the whole group and in subjects with and without insulin resistance.

Results. Acute physical exercise of moderate and high intensity produced beneficial effects on lipid parameters (increase in cholesterol of high density lipoprotein level and reduction of atherogenic index). Increased intensity of physical exercise caused more prominent improvement of lipid profile in subjects without insulin resistance. However subjects with insulin resistance had weaker response to physical exercise than individuals without insulin resistance did and increased intensity of physical exercise did not cause significant improvement of lipid parameters in subjects with insulin resistance.

Conclusion. Response to moderate or high intensive physical exercise may depend on baseline metabolic profile. It should be taken into account under development of preventive programs for modifying risk factors of cardio-vascular diseases and type 2 diabetes mellitus.

513-517 2271

Aim. To study effect of diuretic therapy with furosemide and torasemide on heart rate variability (HRV) and frequency of ventriclar rhythm disorders in patients with chronic heart failure (CHF) complicating ischemic heart disease (IHD).

Material and methods. Patients (n=107) with CHF III-IV functional class (NYHA) complicating IHD were examined. The first group of patients received furosemide, 20-60 mg QD (n=52), the second group received torasemide, 5-20 mg QD (n=55). Analysis of heart rhythm disorders and the basic HRV indicators was performed by ECG 10-minute recordings initially and after 10 days of therapy.

Results. Decrease in time and spectral HRV parameters and increase in daily number of ventricular extrasystoles was found in furosemide treated patients. Improvement of HRV parameters and reduction of daily number of ventricular rhythm disorders was found torasemide treated patients.

Conclusion. Torasemide therapy improves an autonomic regulation of heart rhythm and leads to the reduction of ventricular heart rhythm disorders in patients with CHF complicating IHD.

518-521 437

Atrial fibrillation is a common cardiac arrhythmia. Amiodarone is an effective drug used for atrial fibrillation treatment. Various side effects of this drug including amiodarone-induced thyrotoxicosis are discussed. A clinical case is presented to provide data for the differential diagnosis between types 1 and 2 of amiodarone-induced thyrotoxicosis and to define approaches to the treatment.


522-527 407

Appropriate use of warfarin is not in routine clinical practice despite convincing data of clinical studies on the possibility of effective reduction in frequency of thromboembolic complications associated with nonvalvular atrial fibrillation, particularly ischemic stroke. Confirmation of the efficacy and implementation of measures related to the effect on blood clotting and providing basically new possibilities to reduce the risk of ischemic events expected in the near future.

528-531 456

New possibilities of ACE inhibitors application on the base of international trails review are presented. Traditional therapy areas of ACE inhibitors (hypertension, heart failure) are well known. However recent studies have shown that ACE inhibitors improve prognosis in patients with clinically proved atherosclerosis. This ACE inhibitor ability is a result of their high vasoprotective effect. It provides new clinical possibilities for their use for slowing a progression of diseases associated with atherosclerosis. However this property can not be extended to all ACE inhibitors. Only ramipril and perindopril have a strong evidence base.

532-538 478

The correlation of age-dependent reduction in sex hormones level and changes of cardiovascular system in men was shown recently. High prevalence and various clinical features of age-dependent hypogonadism demands to know diagnostics and management of patients with these disorders. Up to date data about changes of cardiovascular system related to androgen hormone levels reduction are presented. They should help in understanding of pathogenesis of many metabolic and clinical changes. Active attention to the problem of age-dependent hypogonadism, knowledge of organism functions in men with low androgen levels will help to optimize treatment, to avoid of mistakes in patient management, to reduce a risk of severe diseases and finally to improve quality of life and life expectancy of these patients.

539-542 498

The mitral valve prolapse (MVP) is one of the most inconsistent diagnose. In the most cases patients with MVP have the good long-term prognosis, and therapy is aimed at reduction in psychovegetative dysfunction. Careful follow-up and timely cardiosurgical correction should be performed, if necessary, in patients with classical MPV. The choice method in these cases is the mitral valve plasty.


543-549 402

Current views on the efficacy criteria of hyperlipidaemia treatment with statins are considered. Requirements for generics of one of the widely used statin, simvastatin, are discussed. Data of several studies of Simvastol (generic simvastatin) and results of its use for hyperlipidaemia treatment in clinical practice are presented. The results of the studies demonstrate high efficacy of this product as a cholesterol-lowering drug which has pleiotropic effects involving into the atherosclerosis progression.

550-557 437

The role of fixed combinations in the hypertension (HT) treatment is discussed. Theoretical and practical aspects of combination therapy, principles of rational combination therapy are present. Current guidelines on the use of fixed dose combinations, including start antihypertensive therapy are analyzed. Classification of combinations, advantages and limitations of some of them implementation are also presented. Significance of beta-blocker bisoprolol and thiazide diuretic hydrochlorothiazide fixed combination (Lodoz) is shown in HT treatment.

558-564 710

Data of evidence based cardiology including results of international clinical trials on efficacy and safety of the modern calcium channel blocker (CCB), lercanidipine, are presented. Results of these trials show the firm position of lercanidipine in the modern cardiology and confirm that treatment with lercanidipine leads to significant reduction of systolic and diastolic blood pressure (BP) with no effect on heart rate (HR). Peripheral edema (the common side effect of CCBs) occurs rarer with lercanidipine treatment than this with any other CCB treatment. Lercanidipine can be recommended to patients with concomitant diseases due to its additional features.

565-568 457

The most socially significant cardiovascular diseases are recently considered from the standpoint of "cardiovascular continuum". Changes in neurohumoral factors especially activation of the renin-angiotensin-aldosterone system (RAAS) play a key role in the pathogenesis of the cardiovascular continuum. The first drugs that block RAAS were ACE inhibitors. Lisinopril deserves special attention among the ACE inhibitors. Lisinopril — one of the most known and well-studied drugs in this group with proven organoprotective properties. This allows its use in various clinical situations. Lisinopril is used for hypertension treatment long ago and there are a lot of evidences of its high antihypertensive efficacy currently. Lisinopril provides organ protection in various stages of the cardiovascular continuum and improves the life prognosis in patients with ischemic heart disease and chronic heart failure.

569-572 586

Platelets play an important role in the pathogenesis of atherosclerosis. They are involved in atherosclerosis progression and thrombotic complications. That is why antiplatelet therapy is a necessary element of these complications prevention in patients with coronary heart disease. One of the most commonly used antiplatelet agents all over the world is clopidogrel, R2Y12-receptor blocker. It is shown that clopidogrel has insufficient effect in some patients, ie they are resistant to clopidogrel. Genetic causes of resistance to clopidogrel are considered in this review. It is shown that genetic factors related to the metabolism of clopidogrel play an important role in the resistance development. Allel variants of the gene cytochrome CYP2C19 are the main among them. The role of other genes is less studied.

573-577 440

The results of the recently completed clinical studies on the efficacy of atorvastatin in high doses are presented. In these studies high dose atorvastatin therapy was used in patients with acute coronary syndrome, chronic coronary heart disease, and percutaneous coronary interventions. Studies completed in Russia and devoted to efficacy of the high dose atorvastatin therapy are discussed specially.


607-609 389

The ACC/AHA clopidogrel clinical alert about the possibility of ineffective treatment with clopidogrel is discussed. The reason of this resistance to clopidogrel therapy and possible ways to overcome it is considered.

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