Rational Pharmacotherapy in Cardiology

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Vol 8, No 1 (2012)
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4-16 529

Aim. To estimate in a 12-month study mortality and frequency of recurrent cardiovascular events, dynamics of neurological deficit and endothelial dysfunction in patients with the first-time ischemic stroke treated with simvastatin 40 mg/day in acute period of the disease. Materials and methods. The efficacy of high-dose simvastatin (40 mg/day) therapy initiated in acute stage of ischemic stroke was evaluated in 12-month comparative randomized study. Patients of the first group (n=97) received standard stroke therapy , and patients of the second group (n=86) also received standard treatment and simvastatin additionally. Combined endpoint (cardiovascular death + recurrent cardiovascular events + necessity of readmission), dynamics of neurological status and endothelial function were considered.  Results. Primary combined endpoint was achieved in 66 cases in the first group (68.04%) and in 47 (54.65%) in the second one (p=0.043). Neurological status evaluated by National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE) scale, and Scandinavian scales had a faster positive dynamics in patients receiving simvastatin. The same patients revealed more intense and quick decrease in desquamated plasma endotheliocytes. Conclusion. Simvastatin 40 mg/day prescribed along with neuroprotective and antihypertensive treatment in acute stage of ischemic stroke leads to lowering of recurrent cardiovascular events number, positive dynamics of neurological status, regression of endothelial dysfunction reflected by significant decrease in number of circulating desquamated endotheliocytes.

17-22 731

Aim. To study the efficacy and safety of generic valsartan Valz (Actavis Group, Iceland) in comparison with the original valsartan Diovan® (Novartis, Switzerland) in patients with arterial hypertension (HT) of 1-2 degrees and metabolic syndrome. Material and Methods. 30 hypertensive patients (12 men and 18 women) were enrolled in a randomized open-label crossover study. Each patient received generic and original valsartan (80 mg QD) sequentially during 8 weeks. When target blood pressure (BP) level (<130/80 mm Hg) was not reached, a fixed combination of valsartan with hydrochlorothiazide (80/12.5 mg, and then 160/12.5 mg), and bisoprolol 5 mg/daily , if necessary , were used. Treatment efficacy and safety was assessed at visit to doctor every 2 weeks throughout the study. The sequence of drug use was determined by randomization. Results. Systolic BP (SBP) decreased by 27.5 and 27.4 mm Hg from baseline due to generic and original valsartan 8 week treatment, respectively. Diastolic BP (DBP) decreased by 12.8 and 12.9 mm Hg , respectively (p>0.05). Target BP was achieved in 23 patients (77%) in both randomized groups. Serious adverse reaction were not observed during the treatment with both valsartan drugs. Conclusion. The therapeutic equivalence of generic and original valsartan drugs is shown. Therapy based on valsartan (in combination) was safe and effective in 77% of patients with HT of 1-2 degrees and metabolic syndrome.

23-30 483

Aim. To study prevalence of resistance to acetylsalicylic acid, clopidogrel and dual resistance in percutaneous coronary intervention (PCI), to identify clinical risk factors of resistance development, to study effects of concomitant therapy on resistance development, to identify relationship between risk of cardiovascular complications and activity of platelet aggregation, to assess safety of dual antiplatelet therapy , and to suggest possible ways to overcome clopidogrel resistance. Material and Methods. Patients (n=100) with stable angina class II-IV, that were planned for PCI, were included in the study. Patients randomized to group A (n=53) received clopidogrel 75 mg daily for 7 days before PCI, and later were allocated to subgroups of clopidogrel sensitive or resistant depending on platelet aggregation. In resistant subgroup clopidogrel daily dose was increased to 150 mg for the whole next period of observation. Patients randomized to group B (n=47) received a loading dose of clopidogrel 300 mg one day before PCI. Depending on the results of platelet reactivity assessment, patients were split into sensitive or resistant subgroups. Patients of resistant subgroup received the second loading dose of clopidogrel 300 mg before PCI and started to take clopidogrel 150 mg daily after PCI. Patients of sensitive subgroup did not receive the second clopidogrel loading dose and started to take clopidogrel in usual daily dose of 75 mg. The combined endpoint (after 6 and 12 months) included cardiovascular death, recurrent nonfatal myocardial infarction, recurrent angina, acute ischemic stroke, acute impairment of peripheral circulation. Results. Increased reactivity of platelets to acetylsalicylic acid was detected in 21% of patients. Resistance to clopidogrel in both groups was 56%. Double resistance was registered in 8% of patients. The development of resistance to clopidogrel was related with obesity (p=0.014) and hyperglycemia (p=0.017). 4 and 11 cardiovascular events were registered in 6 and 12 months, respectively. Conclusion. To assess efficacy of antiplatelet therapy it is advisable to study platelet aggregation before and shortly after PCI, especially in patients with obesity and glucose metabolism disturbances. Knowledge of changes in platelet aggregation during clopidogrel therapy can be usefull for timely correction of antiplatelet therapy. Increase in clopidogrel dose up to 150 mg a day is one of the possible way to overcome resistance to clopidogrel.

31-36 431

Aim. To assess an incidence of microalbuminuria (MAU) depending on gender and its relation to intrarenal hemodynamic, glomerular filtration rate (GFR), and leptin serum level in essential hypertension (HT). Material and methods. 149 patients (61 men and 88 women, aged 49.4±7.1 years, body mass index 32.2±3.8 kg/m2) with HT degree 2-3 were examined. Clinical characteristics in men and women were comparable. Ultrasonography of intrarenal vessels was performed in all patients. GFR was calculated by isotope nephroangioscintigraphy. Leptin serum level was determined\ by radioimmunoassay. MAU was detected by semiquantitative test. Results were processed with SPSS-11.0 software package. Results. MAU incidence was higher among female hypertensives in contrast to males: 40% vs 26% (p=0.056). Hypertensives with MAU of both genders demonstrated higher both resistance index (RI) and pulsatility index (PI). Gender differences of both RI and PI in patients with MAU were highly significant (p<0.001) at all levels of arterial visualization (renal, segmental and interlobar). Female hypertensives with MAU had lower GFR (79.1±13.2 ml/min/1.73m2) than those without MAU (89.3±17.2 ml/min/1.73m2). Male hypertensives with MAU had higher GFR than those without MAU: 126±32.5 vs 105.4±16.7 ml/min/1.73m2, respectively. Serum leptin level in females with MAU was higher than this in female patients without MAU: 103.5±38.7 vs 76.7±46.4 ng/ml (p=0.04), respectively. Leptin levels did not differ in males with or without MAU. In males MAU positively correlated with GFR (r=0.372, р=0.003), where-as in females – correlation was negative (r=-0.34, р=0.02). Besides, in females MAU correlated with serum leptin level (r=0.48, p=0.01) Conclusion. Female hypertensives with MAU demonstrate more stable elevation of RI and PI in contrast to hypertensive males with MAU. MAU level correlates with GFR in opposite ways: in males positively whereas in females — negatively.

37-44 763

According to recent guidelines, oral dabigatran etexilate is indicated for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). Aim. Based on the RE-LY study to evaluate the cost-effectiveness of dabigatran etexilate versus warfarin prescribed in “real-world” settings from a Russian payer perspective. Material and methods. Markov model simulated AF patients at moderate to high risk of stroke while tracking clinical events and resulting functional disability. Acute event costs and resulting long-term follow-up costs incurred by disabled stroke survivors were calculated using general tariff agreement of Russian obligatory health insurance system and official national statistics. Clinical events, summarized as events per 100 patient-years, expected life years, total costs, and incremental cost effectiveness ratios (ICER) were calculated. Results. Over a lifetime, dabigatran etexilate treated patients experienced fewer intracranial haemorrhages and fewer ischaemic strokes. ICER of dabigatran etexilate was 461,602 roubles per one additional life year versus “real-world” warfarin. Conclusion. This study demonstrates that dabigatran etexilate is a cost-effective alternative to current care for the prevention of stroke and systemic embolism among Russian patients with AF .

45-50 433

Aim. To evaluate the influence of antidepressant therapy with pirlindol on compliance to the long-term treatment and quality of life in patients with cardiovascular diseases and mild to moderate depression. Material and methods. 61 patients with cardiovascular diseases and mild to moderate depression (according to Beck depression scale) were randomized into two groups. Patients of intervention group received pirlindol, while patients of control group did not receive this drug. Compliance to cardiovascular and antidepressant treatment were estimated in 3 and 6 months. Adverse reactions and patients self-assessment of their well-being and global satisfaction in treatmen were also registered.  Results. 24 (75%), 2 (6%) and 0 patients of intervention group continue pirlindol treatment in 1, 3 and 6 months, respectively. In 3 months of observation patients of intervention group took drugs for cardiovascular diseases more often than these in control group (81% vs 72%, respectively , р<0.05), they also less frequently showed adverse reactions (56% vs 72%, respectively ,p=0.01) and more often — improvement of their well-being (65% vs 50%, respectively , р=0.03). Compliance to cardiovascular therapy did not differ significantly in patients of both groups by the end the study.  Conclusion. Antidepressant therapy with pirlindol did not influence compliance to long-term cardiovascular treatment in patients with cardiovascular diseases and mild to moderate depression, apparently because of low compliance to pirlindol therapy.

51-56 480

Aim. To compare vasomotor endothelial function, aortic elastic properties and characteristics of left ventricular (LV) remodeling in patients with isolated systolic (ISHT) and sistolo-diastolic (SDHT) hypertension. Material and methods. Echocardiography , assessment of aorta elastic properties and endothelial vasomotor function were performed in 24 ISHT patients (mean age 73.6 years, mean disease duration 24.8 years) and 52 SDHT patients (mean age 58.0 years, mean disease duration 12.8 years). The age of hypertension onset did not differ significantly in patients of both groups. Results. Aorta elastic coefficient in ISHT patients was 6 times lower than this in SDHT patients (1.00 vs 6.36 mm2/mm Hg, respectively), and vasodilation coefficient (which reflects an ability of vessels to expanding in response to blood flow acceleration) less on 35% (10.9 vs 16.8 standard units, respectively). Patients of ISHT and SDHT groups did not differ in thickness of the interventricular septum (14.8 vs 14.3 mm, respectively), and LV ejection fraction (59.9 vs 60.4%, respectively). However , LV posterior wall thickness in ISHT patients was 3.0 mm less than this in SDHT patients, as well as amplitude of systolic displacement of LV fibrous ring (which reflects LV longitudinal systolic function) was 0.9 cm bigger , respectively. Conclusion. Elderly age, aorta high stiffness, asymmetric LV hypertrophy and impaired LV longitudinal systolic function are typical clinical and functional features of ISHT patients.


57-60 431

Aim. To assess the changes in the costs of treatment of patients with hypertensive crisis (HC) in pre-admission care in Moscow from 2005 to 2010. Material and methods. Comparative analysis of the treatment costs was performed depending on outcomes in patients with HC at Moscow Emergency Medical Care Station named after A.S. Puchkov. HC arresting excluding the need of admission was taken into account in addition to antihypertensive effect and safety in evaluation of pre-admission care efficacy. Results. Introduction in practice of modern algorithms of emergency pre-admission care, supply of ambulance crews with modern antihypertensive drugs reduced the rate of admission from 71% in 2005 to 44% in 2010 among patients with HC. Total savings amounted to 403,691,808 rubles. Conclusion. Introduction of modern technologies in the emergency pre-admission care for patients with HC is economically reasonable.

61-67 575

Aim. To analyze the cost structure for pharmacotherapy of patients with stable angina (SA), in particular, to compare the cost of pharmacotherapy with drugs, both included and not included into the official Standard of care (SC). Material and methods. Medical records of patients with SA (n=100) admitted to the cardiology department of Tver Regional Clinical Hospital in January-July 2010 were studied retrospectivelly. Costs of treatment with drugs specified in SC for patients with SA as well as drugs not included in SC were considered. Costs of pharmacotherapy and cost structure were determined. Pharmacoeconomical methods, especially ABC analysis, were partially used.  Results. Totally 65502.39 ruble was spent for pharmacotherapy of 100 patients with SA. Cost structure was the following: 32679.34 ruble was spent for drugs recommended by SC, 23698.18 ruble — for drugs not included in SC, and 9124.87 ruble — for drugs to treat concomitant diseases which are not taken into account by SC for patients with SA. Conclusion. SA pharmacotherapy counts 50% of the total cost for drugs recommended by SC, 36% — for drugs not included in SC but belonged to pharmacological class presented in SC, and 14% — drugs from pharmacological class not included in SC. In the process of new SC elaboration for SA patients it is necessary to take into account treatment costs of concomitant diseases especially diabetes mellitus which can account up to 9.5% of total treatment cost of SA patients.


68-74 710

The high prevalence of arterial hypertension in association with high and very high cardiovascular risk requires widespread use of combined therapy. Current approaches to selection of combination components of antihypertensive drugs are based the efficacy of these drugs proven in multicenter randomized clinical trials. The triple combination of calcium antagonist, angiotensin II receptor blocker and thiazide diuretic is regarded as the best option for combined therapy in patients with arterial hypertension and ischemic heart disease to reduce cardiovascular risk.


75-80 582

Data of the largest meta-analyzes of beta-blockers use in arterial hypertension is presented. The role of beta-blockers among other basic groups of antihypertensive drugs (thiazide diuretics, calcium channel blockers, ACE inhibitors) is evaluated. Special considerations of beta-blockers use in hypertensive patients with diabetes mellitus and chronic heart failure are discussed. Special attention is paid to bisoprolol.

81-87 732

Early glucose metabolism disorders (GMD) are of interest in development of effective approaches to prevention of type 2 diabetes mellitus (DM). Data of international clinical trials shows that early GMD are an independent risk factor for cardiovascular disease. The possibilities of GMD prevention and early treatment are discussed. Antihyperglycemic medications classification, their mode of action and efficacy are presented from evidence-based medicine point of view. This data confirms that successful DM primary prevention at early stage of GMD reduces the risk of cardiovascular complications.


88-94 509

Arterial hypertension (HT) takes leading position in the structure of morbidity and mortality among the cardiovascular diseases in the economically developed and developing countries of the world. Despite progress in treatment of this disease, a number of people with uncontrolled or resistant HT increases. There is a problem of inefficiency of therapy or lack of patients' adherence to treatment. Therefore, search for new approaches to treatment of HT continues. Current most effective agents for blood pressure control, and possible future antihypertensive agents, are related to groups of agents, which inhibit renin–angiotensin–aldosterone system (RAAS). Novel targets for antihypertensive therapy could include the angiotensin II type 2 and type 1 receptor , neutral endopeptidase, aldosterone synthase, renalase, endothelin receptors, (pro)renin receptors, vaccine against RAAS components. Development of novel agents and approaches to HT therapy is discussed.

95-102 476

For today there are convincing evidences of beneficial effect of ω-3 polyunsaturated fatty acids (PUFA) - eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids – in a number of cardiovascular diseases. Efficacy of ω-3 PUFA was confirmed by results of the large-scale clinical trials. Data on ω-3 PUFA efficacy in heart failure and cardiac arrhythmia were received, besides their well-known hypolipidemic effect. Low level of ω-3 PUFA biomarker , ω-3 index (content of EPA and DHA in erythrocytes), is considered as a risk factor of coronary heart disease as well as a risk factor of fatal arrhythmias. Use of standardized medicinal product with high content of EPA and DHA leads to the positive therapeutic effect in patients with different cardiovascular diseases.

103-109 1035

Study results of a new anti-anginal drug (an inhibitor of sodium channels — ranolazine) are presented. Indications, contraindications, major clinical trials of the drug in patients with ischemic heart disease are considered.

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