Rational Pharmacotherapy in Cardiology

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Vol 9, No 4 (2013)
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354-361 525

Aim. To evaluate dynamics of endothelial vasoregulatory function in type 2 diabetic patients after 6 months of combined treatment with atorvastastin 20 mg/day depending on the disease duration and target lipid levels achievement.
Material and methods. The total of 161 type 2 diabetic patients with dyslipidemia were enrolled into non-randomized open-label study, of which 149 patients were assigned to a group of follow-up (group 1) and 12 to a group of comparison (group 2). All the patients received combined antihypertensive and glucose-lowering therapy. Patients of group 1 were additionally receiving atorvastatin 20 mg/day. Parameters of glucose and lipid metabolism and reactive hyperemia test were assessed in all patients initially and 6 months later.
Results. Patients with newly diagnosed diabetes were more likely to restore endothelial vasoregulatory function as compared to the patients with 1-5 and 6-10 years of diabetes duration (56% vs 42% and 35%, respectively). Patients who reached target lipid levels as compared with those who didn’t, more often revealed normalization of endothelial function (38% vs 33%, respectively). Atorvastatin benefited was more effective in newly diagnosed diabetic patients who had achieved target lipid levels.
Conclusion. Addition of atorvastatin to glucose-lowering and antihypertensive treatment can restore endothelial vasoregulatory function in 6 months in more than half of new-onset type 2 diabetic patients. Maximal effect of combined therapy with atorvastatin is obtained at early stages of diabetes mellitus and at target lipid levels achievement.

362-367 595

Aim. To analyze tactics of statins use in patients with high cardiovascular risk on the base of the PROFILE register data.
Material and methods. Patients (n=274) who were enrolled into the PROFILE register from May, 1st till December, 31st, 2011 were divided into 3 groups: a control group (82 patients who sought medical care in the medical centre for the first time), the main group A (167 patients who were regularly followed-up in the medical centre) and the main group B (25 patients who stopped follow-up in the medical centre over 2 years ago). The incidence rates of statins use and lipid target level achievement, as well as safety of statin therapy were studied in the groups.
Results. 25.6, 70.7 and 52% of patients received statins in control group, main group A, and main group B, respectively. Target levels (according to the clinical guidelines) of the low density cholesterol (LDC) had been reached in 26.3% of patients in the main group A. This characteristic was not valid in the patients of control and main group B because of small size of these groups. Achievement of target LDC level was observed more often in use of statins in moderate and high doses, use of the original drugs, and use of rosu- vastatin. Safety of statin therapy (aspartate and alanine transaminases, creatine kinase activity, and total bilirubin) was comparable in the groups of patients who reached or did not reach target LDC levels.
Conclusion. High cardiovascular risk patients who were regularly followed-up in the specialized medical centre received statins therapy significantly more often. However statins use is often not correspond to the modern clinical guidelines.

368-372 569

Aim. To study the changes of the left (LV) and right (RV) ventricles diastolic function, the segmental LV diastolic function in patients with anemic cardiomyopathy after the iron and selenium drugs therapy.
Material and methods. Patients (n=54) with severe chronic post-hemorrhagic iron deficiency anemia, complicated by cardiomyopathy were treated with iron sulfate and sele- nium. Segmental LV diastolic function was evaluated with pulsed tissue Doppler, and global diastolic function of the LV and RV – with Doppler echocardiography, before and af- ter treatment. Control group contained 16 healthy individuals
Results. Disorders of segmental LV diastolic function, and both ventricles global diastolic function were found in anemic patients with cardiomyopathy. Flow rate rapid filling re- duced by 27.1% compared with this in control (p<0.001), and flow rate of atrial filling increased by 27.0% (p<0.001), and E/A decreased by 42.2% (p<0.001). Iron and se- lenium therapy in patients with anemic cardiomyopathy led to an improvement in diastolic function. LV and RV flow rapid filling increased by 32.2% (p<0.001) and 8.3% (p<0.05), respectively, and LV and RV flow rate of atrial filling reduced by 19.6% and 15.7% (p<0.001), respectively, and LV and RV E/A ratio grew up by 61.5% and 28.2%, respective- ly (p<0.001).
Conclusion. Echocardiography and myocardial tissue Doppler provide early finding of segmental LV diastolic function disorders in anemic cardiomyopathy. Iron and selenium ther- apy leads to improvement of myocardial diastolic function in these patients.

373-378 838

Aim. To study the antihypertensive efficacy of urapidil, as well as to determine the optimal target level of systolic blood pressure (BP) in patients with hypertensive crisis complicated by a hemorrhagic stroke.
Material and methods. Patients (n=86) aged 46-87 years (42 men and 44 women) who were admitted to hospital with hypertensive crisis complicated by a hemorrhagic stroke were included into the study. Patients were randomized into two groups: standard treatment (n=20) or urapidil treatment (n=66). The efficacy of treatment was assessed by clinical data, BP and heart rate dynamics. Patient survival was also assessed.
Results. Mortality in urapidil group was 33% vs 70% in standard therapy group. Systolic BP in urapidil group decreased from 208 (203-222) mm Hg to 159 (149-180) and to
145 (141-153) mm Hg after 20 and 220 minutes, respectively, (p<0.001 for both), and diastolic BP from 108 (102-119) mm Hg to 90 (82-97) and 82 (80-90) mm Hg, re- spectively. Significant BP dynamics was also observed in standard therapy group. The target systolic BP level of 136-147 mm Hg was associated with better patient survival. Conclusion. The patients in urapidil group reached the target BP by the 20-th minute from the start of treatment, and this was accompanied by a better survival.

379-385 541

Aim. To evaluate in open 12 month prospective, randomized study the mortality and recurrent cardiovascular events rate, dynamics of neurological deficit, endothelial dysfunc- tion and renal function in patients with the first ischemic stroke of hemispheric localization after prescription of simvastatin 40 mg daily in the acute stage of the disease. Material and methods. Patients (n=210) above 18 years of age (95 men and 115 women) with acute ischemic stroke were included into the study. Patients were randomized into two groups. Patients of the group 1 (n=105) received standard treatment for ischemic stroke. Patients of the group 2 (n=105) received simvastatin 40 mg/day additional- ly to standard therapy of stroke. Follow-up duration was 12 months. The lipid profile, a number of desquamated epithelial cells circulating in the blood, glomerular filtration rate (GFR) according to MDRD, as well as neurological patient status (Scandinavian Scale, MMSE, NIHSS) were monitored.
Results. During the follow-up period mortality was 18.1% and 15.2% in group 1 and 2, respectively. Composite end point was achieved in 60.9% and 46.6% of patients, re- spectively (p=0.037). Lipid profile did not change significantly in group 1 while patients in group 2 showed a significant decrease in lipid levels. The positive dynamics of neuro- logical status was observed in both groups, however, the most significant - in group 2. Reduction in a number of endothelial desquamated cells was 45.7% in group 2 and 13.3% in group 1 (p=0.00001). GFR increased significantly in patients of group 2.
Conclusion. The long-term treatment with simvastatin in combination with neuroprotective and antihypertensive therapy in patients with acute ischemic stroke leads to decrease in the incidence rate of clinically relevant events, improvement of endothelial function, neurological status and prognosis.

386-389 671

Aim. To study effects of trimetazidine on the left ventricular diastolic dysfunction in patients with combination of ischemic heart disease (IHD) and arterial hypertension (HT). Material and methods. Patients with IHD and HT (n=154) were divided into two treatment groups. Patients of the main groups (n=72) received standard therapy and trimetazi- dine 35 mg twice a day. The patients of the control group (n=82) received only standard therapy. Echocardiographic parameters, including mitral Doppler flow indices were as- sessed at baseline and after 2 months.
Subgroups of patients were identified by type of left ventricle diastolic function according to echocardiographic data. Changes in echocardiographic indicators were evaluated in these subgroups separately and compared in the main and control groups.
Results. The subgroups of patients with impaired relaxation (n=54), pseudonormalization (n=48) and restriction (n=52) were identified in the main and control groups according to echocardiographic data. A significant increase in the period of early left ventricle filling (27.6%, p<0.05) and the ratio of the two phases of left ventricle filling (37.8%, p<0.001) were found in patients with impaired relaxation treated with trimetazidine. Other studied parameters of mitral flow in the other patient subgroups were not significantly changed. Conclusion. Trimetazidine 70 mg daily in the 2 month treatment of diastolic heart failure in patients with IHD and HT resulted in significant improvement of some indicators of mitral blood flow only in patients with type I diastolic dysfunction (impaired relaxation).

390-397 628

Aim. To study the morphological features of loose fibrous connective tissue (LFCT) and myocardial contractility in patients with mitral valve prolapse before and after magnesium orotate course.
Material and methods. Patients (n=59) with mitral valve prolapse and the phenotype of undifferentiated connective tissue dysplasia (UCTD) were included into the study. A comprehensive morphological analysis of skin biopsy samples was performed to assess morphological and functional changes of LFCT. Standard echocardiography with the assessment of mitral flow was performed in all participants at baseline and after 8 weeks of magnesium orotate intake.
Results. According to morphometry increase in proportion of amorphous matrix was found in LFCT sections after 8-week magnesium orotate course compared to baseline (38.6±0.4% and 23.9 ± 0.4%, respectively; p<0.001). According to the echocardiography increase in the end-diastolic (from 4.9±0.04 cm to 5.05±0.03 cm; p<0.05), and the end-sys- tolic (from 2.9±0.04 cm to 3.0±0.03 cm; p<0.01) left ventricular diameters was observed after 8 weeks of treatment as well as improvement of left ventricular diastolic func- tion (E/A raised from 1.42±0.02 to 1.79±0.04; p<0.01).
Conclusion. In patients with mitral valve prolapse and UCTD the 8-week magnesium orotate course led to a significant increase in amorphous part of the matrix, improvement of diffusion ability and architectonics of the connective tissue that determines the improvement of flexibility and extensibility.

398-403 987

Aim. To compare direct medical costs of dabigatran and warfarin therapy in patients with non-valvular atrial fibrillation (NVAF) during preparation for elective cardioversion. Material and methods. An open non-randomized study was conducted to evaluate direct medical costs (cost of drug, cost of the international normalized ratio (INR) adjust- ment in outpatient clinic, cost of visits to cardiologist). Patients (n=62) with persistent NVAF (AF paroxysm duration > 48 hours) were enrolled. All of them requested medical as- sistance and were decided to perform an elective cardioversion. The patients received warfarin (n=32) or dabigatran (n=30). The patients of the both groups were similar in the main clinical characteristics and thromboembolic risk levels according to CHA2DS2-VASc scale.
Results. Treatment duration before elective cardioversion was 21±2 and 30.5±4.5 days for dabigatran and warfarin groups, respectively (p<0.05). Average costs of visits to cardiologists were 3,720 and 744 RUB in warfarin and dabigatran groups, respectively (p<0.05), and drug costs were 53.63 and 1,172.01 RUB, respectively (p<0.05). The costs of laboratory INR monitoring were 3,058 RUB in warfarin group. Total costs per patient were 6,831.63 and 1,916.01 RUB in warfarin and dabigatran groups, respectively (p<0.05). Conclusion. In the real clinical practice in patients with NVAF dabigatran antithromboembolic therapy substantially reduces direct medical costs in comparison with warfarin ther- apy during preparation for elective cardioversion. Dabigatran therapy reduces time from the decision of elective cardioversion and antithromboembolic therapy start to car- dioversion performance.


404-408 491
The clinical significance  of CYP2C19 genetic polymorphism, associated with the violation of the formation of the active clopidogrel metabolite, for efficacy and safety of this drug in cardiology practice is discussed. Approaches to antiplatelet agent choice according to pharmacogenetic CYP2C19 testing, as well as the indications for this approach use in clinical practice are presented. Consideration of these testing results should increase the efficacy and safety of antiplatelet treatment.


409-416 643
The evidence base of statin therapy in primary and secondary prevention of ischemic stroke is surveyed. Results of classical trails with statins in ischemic stroke prevention as well as results of meta-analyses are discussed.
417-419 500
Mechanisms of atrial fibrosis including the role of serotonin in the development of this lesion in patients with atrial fibrillation are presented. New approaches to the treatment of atrial fibrillation aimed at atrial fibrosis reduction are discussed.
420-426 680

Optimization of the pharmacotherapy in preoperative period is the cornerstone of the concept of risk modification of cardiovascular complications in the perioperative period. Therefore, special attention has recently been focused on the use of beta-blockers in the postoperative period. Nowadays convincing evidence base for the use of this class of drugs in the perioperative period that was the basis for the development of clinical guidelines is accumulated. Moreover, results of large randomized trials of beta-blockers are controversial. This has resulted in significant differences in the classes of recommendations and levels of evidence.
Analysis of the results of basic researches and the provisions of recommendations of the international and national professional medical societies on the use of beta-blockers in patients with cardiovascular disease to reduce the risk of cardiac complications in the perioperative period for planned extracardiac surgical procedures is presented.

427-432 515
The results of the main large controlled trials that had proven effect of ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) on cardiovascular diseases outcomes are evaluated. Data of the recent meta-analyzes comparing ACEi and ARB effects on the life prognosis in patients of the high cardiovascular risk are presented. Better validity of ACEi efficacy versus this of ARB is concluded.
433-438 563
Indirect comparisons of new oral anticoagulants are performed with focus on their safety. Apixaban, an oral inhibitor of Xa factor, nowadays can be considered as a drug with very good safety profile according to randomized trials results and performed indirect comparisons.


439-443 823
Review of current ideas about the role of acetylsalicylic acid (ASA) in the primary prevention of cardiovascular disease is presented. Data on reduction in malignant neoplasms incidence rate in long-term use of the drug, as well as prospects for further study of ASA in the primary prevention are considered.
444-447 701
Randomized controlled trials have clearly demonstrated the efficacy of statins in reduction of serum low density lipoprotein cholesterol level by 25-50% from the baseline. Statins may increase the risk of diabetes mellitus (DM) in long-term therapy and use of high doses. Diabetogenic action is statins class effect and does not depend on their hydrophobic or hydrophilic properties. However, the use of statins in patients with DM is obligatory. The statins diabetogenic  risk is exaggerated and we will continue to treat our patients with statins.
448-454 752
Amlodipine combines the most important clinical effects of calcium antagonists with minimal side effects of both its ATC class  and drugs of previous generations. Its high antihypertensive  activity is not in doubt. Proven ability to improve long-term prognosis is a priority when choosing of amlodipine for treatment of hypertensive patients. This is particularly important for the primary prevention in the presence of both risk factors and associated clinical conditions.  Amlodipine therapy significantly reduced cardiovascular events incidence in patients with atherosclerosis, even if they have no arterial hypertension. The likely rationales for this amlodipine effect are its vasoprotective properties, ability to re- duce vascular stiffness and to slow down the progression of atherosclerosis.
455-458 484
The problem of varenicline use in patients with cardiovascular diseases is discussed. Results of large clinical trials and meta-analyses with varenicline have proven its high efficacy for treatment of nicotine addiction in adults and a small number of side events. Varenicline is the main agent for pharmacotherapy of nicotine addiction due to its high efficacy and advantages of smoking cessation. However careful monitoring of its side effects is needed in these patients.

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