Rational Pharmacotherapy in Cardiology

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Vol 10, No 5 (2014)
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470-480 742

Aim. To evaluate outcomes and risk of their occurrence in patients with atrial fibrillation (AF) within 12 months of follow-up in actual outpatient practice.

Material and methods. A total of 3690 patients with AF, arterial hypertension (HT), ischemic heart disease (IHD) and chronic heart failure (CHF) consulted by general practitioners and cardiologists of three outpatient clinics of Ryazan, were enrolled into the outpatient REgistry of CardioVAScular diseAses (RECVASA). 530 of 3690 (14.4%) patients had the diagnosis of "atrial fibrillation" in their outpatient charts. Estimation of the end points within 12 months after inclusion into the registry was performed based on the data received from the contacts with patients or a documented fact of death.

Results. 39 (7.4%) patients had died during this period [30 (76.9%) of them due to cardiovascular causes], 18 (3.4%) – had undergone stroke, 3 (0.6%) – myocardial infarction, 2 (0.4%) patients had cardiovascular surgery. There were 63 hospitalizations due to cardiovascular diseases (CVD). AF did not lead to significant increase in cardiovascular death risk [odds ratio (OR)=1.31, p=0.21] and stroke risk (OR=1.64, р=0.09) within 12 months after inclusion into the registry, but the risk of hospitalization due to CVD was significantly higher(OR=2.88, р=0.0001). Permanent AF significantly increased the risk of stroke (OR=2.07, р=0.04). Such factors as diabetes, prior stroke, systolic blood pressure (SBP)<110 mm Hg and heart rate (HR)≥90 bpm significantly increased all-cause death risk (OR=2.49, р=0.008; OR=2.46, р=0.01; OR=7.6, р=0.003; OR=15.3, р=0.01, respectively). Patients treated with ACE inhibitors or angiotensin receptor blockers (ARB) had lower all-cause and cardiovascular death risks: OR=0.38, р=0.01 and OR=0.25, р=0.02, respectively. Other drugs revealed no significant influence on prognosis.

Conclusion. According to the outpatient registry RECVASA data such factors as permanent type of AF, diabetes mellitus, prior stroke, SBP<110 mm Hg and HR≥90 bpm, ACE inhibitors/ARB prescription significantly influenced prognosis in patients with AF. Estimating outcomes in AF patients, combination with HT, IHD, CHF and non-cardiac comorbidities must be taken into account as well as peculiarities of these diseases drug treatment.

481-487 537

Aim. To study the rate and characters of masked arterial hypertension (HT) and masked ineffectiveness of HT treatment in industrial workers within annual preventive examination.

Material and methods. Workers (n=185) with normal office blood pressure (BP) <140 and <90 mm Hg were enrolled into cross-cohort study of industrial workers of large enterprise engaged in activity with harmful and/or dangerous conditions (n=477; mean age 53.2±5.5 years). Standard survey, anthropometry, ambulatory BP monitoring (ABPM), blood chemistry, electrocardiography, and echocardiography were performed. Criteria of masked HT and masked HT in treated subjects were the level of office BP <140 and <90 mm Hg in combination with mean BP during the operational period ≥135 and/or ≥85 mmHg. Patient characters significantly associated with this ratio of office BP and BP during the operational period were considered as features of isolated increase in ambulatory BP level.

Results. The rate of masked HT among workers with normal office BP was 10.8%, and masked HT among treated subjects was 34.6%. Workers with masked HT, in contrast to the normotensive workers according to the office BP and ABPM measurements, had a higher left ventricular mass index (in males 129.0±21.2 vs. 109.5±28.8 g/m2, respectively, in women 105.2±43.2 vs. 82.4±25.3 g/m2, respectively, p<0.05), and higher body weight (85.4±13.3 vs. 81.3±10.1 kg, respectively; p=0.05). Treated subjects with masked HT, unlike workers with effective antihypertensive therapy had a higher body weight (89.4±16.1 vs. 85.4±15.8 kg, respectively, p<0.05), higher levels of triglycerides (1.56±0.95 vs. 1.23±0.55 mmol/l, respectively, p<0.01) and uric acid (388.5±89.5 vs. 357.2±84.5 mmol/l, respectively, p<0.05), more prominent left ventricular hypertrophy, lower incidence of ischemic heart disease, but higher number of persons taking ACE inhibitors. Occupation and work features were not characters of the masked HT and masked ineffectiveness of HT treatment.

Conclusion. Masked HT and masked HT in treated subjects (masked ineffectiveness of HT treatment) can occur in almost a half of industrial workers with normal office BP. Ambulatory BP measurement methods, especially ABPM, as well as standard risk factors detection are necessary for early revealing of HT phenotypes during preventive examination.

488-494 576

Aim. To study the role of immune inflammatory reactions and endothelial dysfunction in myocardial remodeling and progression of ischemic heart disease (IHD).

Material and methods. 413 patients with IHD including 251 patients with stable and 162 patients with unstable angina were enrolled into the study. 55 healthy subjects were included into control group. Myocardial remodeling was studied by echocardiography. Immune inflammatory reactions were studied by detection of primary and secondary products of lipid peroxidation and antioxidative enzymes, pro- and antiinflammatory cytokines. Endothelial function was assessed by endothelium-dependent vasodilatation (EDVD) and levels of endothelin-1 (ET-1) and adhesion molecules.

Results. Correlation analysis showed relations of indicators of lipid peroxidation and antioxidative enzymes with proinflammatory cytokines – interleukin-1β, interleukin-6, tumor necrosis factor-alpha (TGF-α) (r=-0.39; -0.54; -0.42, respectively; р<0.05) and EDVD, ET-1 and E-selectin (r=-0.44; 0.52; 0.49, respectively; р<0.05). Interrelations of lipid peroxidation products and glutathione peroxidase with hemodynamic parameters were found out, as well as between TGF-αconcentration and indicators of myocardial remodeling. Strong correlations were revealed between parameters of endothelial and myocardial functions.

Conclusion. The role of immune inflammatory reactions and endothelial dysfunction in myocardial remodeling and IHD progression was established on the basis of the correlation analysis.

495-499 796

Aim. To study the efficacy of loop diuretic torasemide compared with furosemide consisting of combination therapy in patients with chronic heart failure (CHF).

Material and methods. Inpatient and outpatient patients (n=136; 80 men and 56 women) with CHF class 2-3 (NYHA) living in different regions of Kazakhstan were included into the study.

Results. More pronounced decrease in edema syndrome, significant decrease in the rate of maladaptive myocardial remodeling, increase in systolic function by 8.2%, improving quality of life by 30.1% took place during combination therapy including loop diuretic torasemide compared with furosemide.

Conclusion. The loop diuretic torasemide consisting of combination therapy has a positive effect on myocardial remodeling and improves quality of life in patients with CHF class 2-3 (NYHA).


500-504 575

Aim. To evaluate an adequacy of dual antiplatelet therapy (DAPT) in patients with acute coronary syndrome (ACS) with ST segment elevation and bare metal stent implantation after hospital discharge.

Material and methods. 311 patients with ACS with ST segment elevation were included into the study. All of them underwent percutaneous coronary intervention with bare metal stent implantation. The information was obtained by the telephone survey.

Results. 54.5% of patients received DAPT during 12 months. 43.8% of patients also received combination of clopidogrel and acetylsalicylic acid, but changed medicinal products of clopidogrel due to different reasons. 1.7% of patients received acetylsalicylic acid only.

Conclusion. More than 50% of patients received recommended DAPT at that they preferred generic drugs of clopidogrel original one.

505-508 506

Aim. To assess the choice of initial pharmacotherapy of uncomplicated mild to moderate arterial hypertension (HT) in Moscow primary care as well as to clear up the influence of regulatory measures on this choice.

Material and methods. Results of two similar surveys conducted in 2011-2012 (452 respondents) and 2013-2014 (273 respondents) were compared to estimate preferences of Moscow primary care physicians regarding initial antihypertensive agents for therapy of uncomplicated mild to moderate HT taking into consideration an influence of regulatory requirement to prescribe medicinal products by international nonproprietary name (INN) since July 2012. All participants were proposed to write down their preferred antihypertensive agents for initial mono- or combined therapy of mild to moderate HT with moderate cardiovascular risk and absence of compelling indications.

Results. Angiotensin converting enzyme inhibitors (ACEI) remained the leading class of antihypertensive agents, though their popularity slightly but significantly declined from 44.4% in 2011-12 to 37.2% in 2013-14 (р<0.05). Angiotensin receptor blockers partially displaced the leaders and increased their popularity from 11.3% in 2011-12 to 18.0% in 2013-14 (р<0.01). ACEI/diuretic combination remained on the 3rd position (16.4% and 15.3% respectively). Beta-blockers and diuretics as monotherapy shared 4th and 5th places in this rating. Calcium channel blockers popularity among Moscow prescribers remained unchanged and poor – 2.1%. The most popular medicine by trade name was Noliprel, perindopril/indapamide fixed combination, – 14.0% and 13.7% of respondents in 2011-12 and 2013-14, respectively. The share of medicine products recommended by INN went up from 11.9% to 22.8% among top-10 popular medications (р<0.01).

Conclusion. Blockers of renin-angiotensin-aldosterone system remain the leading drugs for the initial treatment of uncomplicated mild to moderate HT without compelling indications among Moscow primary care physicians. Regulatory requirement to prescribe medicinal products by INN was associated with significant increase in the share of drugs recommended by INN, though this effect was less than expected one.


509-512 617

Clinical case study is described. Patient D, 55 years old, applied to the Lipid clinic of State Research Centre for Preventive Medicine because of low blood cholesterol level. Results of the differential diagnosis of the hypocholesterolemia syndrome by using exomic sequencing are presented. This method allows to sequence the majority of regions of genome containing exons, protein-coding parts of genes. Heterozygous mutation in the gene for APOB (5 nucleotides deletion) was found out in the patient by using exomic sequencing. This mutation leads to a premature stop codon with violation of apolipoprotein B-100 synthesis and causes inherited monogenic disease - family hypobetalipoproteinemia.

513-524 771

Statins, the most common drugs for reduction in lipid levels, are “strategic” medicinal products for the treatment and prevention of cardiovascular diseases caused by atherosclerosis. The milestones of lipid-lowering therapy history are presented as well as its contemporary aims and their implementation with focus on rosuvastatin. Data of recent metaanalysis regarding statins efficacy in primary and secondary prevention of cardiovascular complications, good safety and tolerability profile were presented. Treatment of patients with acute coronary syndrome with modern statins in high doses is discussed specially. Clinical case study of long-term treatment with rosuvastatin 20 mg/day is described. Frequency of statin prescriptions and achievements of target lipid levels in real medical practice among population of Russian patients is evaluated according to results of LIS study and PROFILE registry. Results of Russian studies of therapeutic equivalence of generic drug with original rosuvastatin are presented.

525-529 626

Aim. To study the efficacy of rosuvastatin in dyslipidemia correction in patients after Q-wave myocardial infarction (Q-MI).

Material and methods. 40 patients (aged 52.7±9.4 years old) were included into the study after 10-14 days of the acute Q-MI onset. Determination of blood lipids profile, alanine and asparagine transaminase levels was included into the initial examination. Rosuvastatin in a fixed dose of 20 mg/day was prescribed to the patients as a part of the standard therapy. Depending on the dynamics of the investigated parameters the individual doses of rosuvastatin were adjusted from 10 to 40 mg/day after 1 month of therapy. Final evaluation of blood lipids profile and transaminase levels was performed in the next 2 months of therapy.

Results. Rosuvastatin 20 mg/day for 1 month in patients with an acute Q-MI provides a significant decrease in low-density lipoprotein (LDL) cholesterol level by 21.4%, and achievement of target levels of this parameter in 59.5% of patients. Rosuvastatin dose adjustment was required in 48.6% of patients after 1 month of therapy. Individually adjusted rosuvastatin doses provided the achievement of LDL cholesterol target levels by the end of the third month of treatment in 91% of patients. Elevated liver transaminase levels were observed in 7.5% of patients after 1 month of treatment. There were no new cases of adverse events after 3 months of therapy.

Conclusion. Rosuvastatin 10-40 mg/day is effective and safe medicine for the treatment of dyslipidemia in patients after acute Q-MI.


530-533 500

News from Congress of the European Society of Cardiology (Barcelona, 2014) is highlighted. Results of recent controlled clinical trials, new clinical recommendations and registers data that were presented at the Congress are discussed.


534-539 588

Aim. To evaluate the association of serum resistin with morphological and functional indices of hypertrophic myocardium in patients with type 2 diabetes and chronic heart failure (CHF) with preserved left ventricular ejection fraction.

Material and methods. Patients (n=60; 12 men and 48 women) with type 2 diabetes and ischemic heart disease and CHF class II-III (NYHA) were included into the study. Clinical, laboratory and instrumental examinations, as well as determination of serum resistin were performed in all patients.

Results. Positive correlation was found between serum resistin level and left ventricle end-diastolic pressure (LV EDP; r=0.43; p=0.02) in patients with concentric left ventricular hypertrophy (LVH). Negative correlation was found between serum resistin level and LV EDP (r=-0.61; p=0.000) in patients with eccentric LVH. A number of supraventricular extrasystoles positively correlated with the serum resistin level (r=0.34; p=0.033) in patients with concentric LVH.

Conclusion. The role of "physiological" levels of resistin in the formation of cardiovascular indicators of the hypertrophic myocardium as well as possible prognostic significance of different levels of resistin for optimization of therapy are shown in patients with type 2 diabetes with CHF.


540-547 556

Approaches to the total cardiovascular risk calculation based on the actual clinical recommendations are presented as well as the application of risk categories for the choice of strategy of dyslipidemia correction. The use of statins as lipid-lowering therapy in patients with acute coronary syndrome and coronary angioplasty are also discussed.

548-553 663

Optimization of pharmacotherapy in the preoperative period is the cornerstone of the risk modification of cardiovascular complications in the perioperative period. Particular attention has recently been focused on statins use. Evidence base of this drugs class use in the perioperative period serves as the basis for the development of clinical guidelines. However, the results of large randomized trials of statins are controversial. Ambiguous interpretations of these trials data has resulted in significant differences in the classes of recommendations and levels of evidence. Analysis of results of the basic clinical trials and the guidelines of international and national medical societies on the use of statins in patients with cardiovascular diseases to reduce the risk of cardiac complications in the perioperative period in planned extracardiac surgery is presented.

554-558 630

History of thrombolytic therapy is shortly reflected, main trials of various thrombolytics in acute ST-segment elevation myocardial infarction (STEMI) are analyzed. Perspectives of modern thrombolytic therapy in patients with STEMI are discussed.


559-564 1660

Results of clinical trials devoted to urapidil, antihypertensive drug having central and peripheral mode of actions are reviewed. Target groups of patients for urapidil use are specified. Dosage regimen and methods of urapidil use in different clinical situations with acute increase in arterial blood pressure are described in details.

565-571 1084

Rationale and benefits of the use of the ACE inhibitor lisinopril in the clinical practice as an antihypertensive drug are considered. Special attention is paid to the organ protective effects of lisinopril and its application in some clinical situations (combination of hypertension with chronic obstructive pulmonary disease, elderly patients, and concomitant liver diseases).



573-574 322

Vladimir G. Kukes is 80.

575 327
To the anniversary of Professor Alexander G. Avtandilov.

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