Rational Pharmacotherapy in Cardiology

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Vol 9, No 3 (2013)
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217-226 631

Aim. To evaluate postprandial changes of lipid and glucose profiles, inflammation markers levels and flow-mediated vasodilatation in patients with metabolic syndrome (MS) and to estimate acarbose course treatment efficacy in glucose intolerant patients.
Material and methods. A total of 114 MS patients (83 men, 31 women) were examined, MS was associated with impaired glucose tolerance (IGT) in 55 cases. At the first stage postpran- dial dynamics of flow-mediated dilation (FMD), lipid profile parameters, inflammation markers and insulin levels were estimated. At the second stage patients with MS and IGT (n=55) were randomly assigned to the two groups of treatment. Patients of the first group (n=28) had non-drug treatment. Patients of the second group (n=27) received acarbose 300 mg/day for 3 months in addition to recommendations for lifestyle change. 3 months later postprandial values of lipid and glucose profiles parameters, inflammation markers levels and FMD were reassessed. Results. MS patients with IGT revealed maximal disorders in metabolic parameters during postprandial period: increase in the plasma levels of total cholesterol by 6.1%, high density lipoproteins – by 1.7%, and triglycerides – by 27.87%, increase in atherogenic index by 4.8%, and plasma concentrations of glucose – by 54.7%, insulin – by 30.2%, HOMA index – by 73.3%, as well as concentrations of C-reactive protein (CRP) – by 49.7%, tumor necrose factor alpha – by 20.8%, and interleukin-6 (IL-6) – by 51.9%. FMD decreased by 34.3%.
After 12 weeks of the acarbose treatment we had revealed positive dynamics of studied indices in postprandial period as compared to an only non-drug management: levels of glucose in- creased by 24.1% vs 44.4%, insulin – by 14.4% vs 24.4%, CRP – by 19.9% vs 36.6%, IL-6 – by 25.1% vs 41.7%; postprandial FMD decreased by 18.9% vs 31.1%.
Conclusion. Prescription of acarbose 300 mg/day for 12 weeks in glucose intolerant patients is characterized by less significant postprandial increase in insulin resistance, inflammation mark- ers (CRP and IL-6) levels, less decrease in flow-mediated vasodilatation with no influence on lipid metabolism parameters.

227-235 741

Aim. To study antihypertensive efficacy and safety of valsartan-based therapy as well as influence of treatment on several aspects of sexual function.
Material and methods. Hypertensive patients (n=650) in 53 medical institutions of Russia were enrolled to the prospective multicenter observation study, 37.5% of smokers and 62.5% non-smokers. The evaluation of therapy efficacy was based on analysis of systolic (SBP) and diastolic (DBP) blood pressure (BP) changes. Safety and compliance of treatment was also analyzed. The evaluation of sexual function was performed with 5 universal questions selected form the International Index of Erectile Function. These ques- tions could be asked in both men and women. The valsartan dose was 80–320 mg OD. A combination of the valsartan with hydrochlorothiazide (12.5–25 mg/d), amlodipine (5–10 mg/d) or any other antihypertensive was allowed.
Results. Significant similar decrease of SBP and DBP was observed in smoking and non-smoking patients (37.4/17.8 and 36.7/16.5 mm Hg respectively, р<0.01 vs baseline). Differences in SBP and DBP changes were not significant between groups. Target BP level (<140/90 mmHg) was reached in 81.9% smokers and 76.0% non-smokers.
After 20 weeks of treatment the number of patients without sexual activity and with 1–2 successful sexual attempts in the last 4 weeks significantly decreased from 44.7 to 32.8% and from 29.1% to 23.2%, respectively (р<0.05). Significant increase in the number of patients with 5–6 and 7–10 successful sexual attempts was observed (from 6.1 to 13.6% and from 3.2 to 5.9% respectively, р<0.05). The treatment resulted in significant increase in the number of patients, who evaluated their sexual life satisfaction as ″very satisfied″ (from 8.2 to 14.8%, <0.01).
Conclusion. Comparable antihypertensive efficacy and safety were demonstrated for valsartan based therapy in smoking and non-smoking patients. During the course of treatment there was a significant improvement of sexual function and general satisfaction with sexual life in patients with arterial hypertension, which could have favorable long-term consequences in increased compliance to the antihypertensive therapy.

236-240 1349

Aim. To study efficacy and safety of calcium channel blocker, S-amlodipine, in combination with β-blocker, atenolol, in patients with arterial hypertension (HT) 1-2 degree com- pared to fixed combination of racemic amlodipine and atenolol.
Material and methods. Patients (n=31, 7 men and 24 women) with HT 1–2 degree were included into the study. The patients were randomized into two groups by the com- binations sequence. Treatment with each combination lasted 4 weeks. Office blood pressure (BP) was assessed at baseline and at the end of the treatment periods, possible side effects were registered.
Results. All patients completed the study. Both combination of S-amlodipine+atenolol and fixed combination of racemic amlodipine+atenolol reduced systolic (in average, -15.9 and -12.7 mm Hg, respectively) and diastolic (in average, -7.3 and -5.3 mmHg, respectively) BP significantly. Heart rate also decreased during therapy (in average, -3 and -4 bt/min, respectively). The differences between combinations BP and heart rate effects were not significant. 8 and 16 adverse events were registered during S-amlodipine+atenolol and racemic amlodipine+atenolol therapies, respectively Conclusion. Combination of S-amlodipine+atenolol, as well as combination of racemic amlodipine+atenolol are effective in the treatment of patients with HT 1-2 degree, however combination with S-amlodipine has less number of adverse events.

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Aim. To investigate association between 9p21.3 locus single nucleotide polymorphisms (SNPs) and coronary atherosclerosis severity and long-term outcomes after percutaneous coronary intervention (PCI) in patients with myocardial infarction (MI).
Material and methods. A total of 255 Caucasian patients (211 male, 44 female; aged up to 65 years, on the average 52.56±7.98 years) with MI were recruited into the study from 01.01.2009 to 30.06.2010. All participants were included into the study after written informed consent. Genome DNA was extracted from leukocytes of venous blood by the phenol-chloroform extraction method. Two SNPs rs10757278 and rs1333049 (locus 9p21.3) were tested by real-time polymerase chain reaction (PCR) according to protocol (probes TaqMan, Applied Biosystems, 7900HT). The coronary angiograms were reviewed by independent angiographers who were blinded to the results of the genotyp- ing (Philips Allura Xper FD10). The total number of lesions, Gensini score and SYNTAX score were derived. Follow-up lasted two years.
Results. Locus 9р21.3 genotypes CC rs1333049 and GG rs10757278 demonstrated a direct strong association with severity of coronary atheromatous burden (left main coro- nary artery stenosis, total number of lesions, Gensini score). There are not influence of locus 9p21.3 on mortality, recurrent MI, hospitalization due to unstable angina, repeated PCI, stroke during follow-up period (6, 12, 24 months). Frequency of the genotype СС rs1333049 among patients with recurrent MI was 20% (without recurrent MI — 27.4%; р=0.54); with hospitalization due to unstable angina — 27.5% (without hospitalization — 26.4%; р=0.82); with repeated PCI — 24.0% (without repeated PCI — 27.2%; р=0.97); among died patients — 29.8% (among survived ones — 26.4%; р=0.76). Frequencies of the genotype GG rs10757278 were similar: recurrent MI (yes — 18.8%; no — 26.4%; р=0.49); hospitalization due to unstable angina (yes — 28%; no — 25.3%; р=0.42); repeated PCI (yes — 23.7%; no — 26.3%; р=0.98); death (yes — 28.6%; no — 25%; р=0.51). Conclusion. Locus 9р21.3 genotypes CC rs1333049 and GG rs10757278 revealed significant association with severity of coronary atheromatous burden in patients with MI. There was no relationship between these genotypes of locus 9р21.3 SNPs and long-term PCI outcomes.

247-250 690

Aim. To assess the risk factors of statin-associated muscle damage in patient with ischemic heart disease.
Material and methods. 258 patients with ischemic heart disease treated with statin were included into the study. Total plasma creatine kinase levels were measured and SLCO1B1*5 genotyping was performed. Relationship between statin therapy and adverse events was evaluated by Naranjo algorithm.
Results. Patients with muscle symptoms received statins significantly longer (48.8 vs 11.9 months, р<0.0001) and in higher doses, than patients without muscle pain/weakness. There were not significant differences in creatine kinase levels between patients with and without muscle symptoms. Patients with SLCO1B1*5 genotype were revealed in both groups, but more often (58%) among patients with muscle symptoms. Patients with abnormal C allele having muscle symptoms received statins significantly longer, than these without muscle signs (54.7 vs 13.9 months, р=0.0028).
Conclusion. Association between occurrence of muscle symptoms and SLCO1B1*5 allele carriership, statin dose and therapy duration was revealed. Creatine kinase examination was not valuable for finding of statin-induced muscle damage.

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Aim. To evaluate the economic effectiveness of the combined two-drug antihypertensive therapy in patients with arterial hypertension (HT) and high cardiovascular risk by Markov’s modeling.
Material and methods. Patients (n= 65; 19 males and 46 females) with essential HT accompanied by metabolic disorders, history of previous ineffective antihypertensive therapy were included into the study. Patients were randomized into 2 groups. Group V/A was treated with valsartan and amlodipine in fixed-dose combinations of 160/5 and 160/10 mg depending on blood pressure (BP) level. Patients of group L/A were treated with losartan 100 mg and amlodipine 5 or 10 mg daily. Treatment duration was 24 weeks. Changes in BP level, and left ventricular hypertrophy (LVH) regression were assessed. Economic evaluation was performed on the basis of modeling with specialized software Decision Tree 4.xla.
Results. Effect of the two variants of combination therapy on LVH was used to estimate treatment effectiveness and to build the model. Patients were distributed according to the left ventricular mass (LVM) at baseline and after 24 weeks of therapy. Significant decrease in LVM was observed in V/A group: from 225.1±71.7 to 186.3±44.5 g (p<0.05). There was no LVM dynamics in L/A group. The model took into account economic and frequency factors for 10 years forecast. V/A therapy is able to prevent 94 deaths, 22 strokes, and 64 myocardial infarction per 1000 patients. Absence of need in treatment of these prevented events can save about 5.5 million RUR for every 1000 patients. It would reduce the total costs per patient during 10 years. V/A therapy is able to save maximal number of quality adjusted life years (QALY) due to LVM regression (5.016 years). L/A combination is the most economical variant of pharmacotherapy due to low cost of treatment (16.491.25 RUR per 1 QALY). It would take 286.698.7 RUR additionally for one additional QALY in the treatment with V/A, and it is economically effective.
Conclusion. Treatment with V/A fixed-dose combinations shows higher antihypertensive and cardioprotective efficacy in comparison with that in L/A combination therapy. It reduces a risk of acute myocardial infarction, stroke and death more effectively. V/A therapy gains the maximal number of life years and QALY due to LVM regression.
L/A combination is the most cost-effective in terms of cost of life year gained and QALY. L/A combination allows to save costs due to lower cost of treatment.

258-264 1005
Aim. To study the right heart remodeling and level of N-terminal brain natriuretic peptide (Nt-proBNP) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Material and methods. Patients (n=79) after pulmonary embolism were included into the study. The main group consisted of patients (n=43) with an increase in systolic pulmonary artery pressure (SPAP) >30 mm Hg: 30 (37.9%)  patients had pulmonary hypertension (PH) degree I, and 13 (16.5%)  — PH degree II–III. Group of comparison con- sisted of 36 patients expired pulmonary embolism and having SPAP <30 mm Hg. The control group consisted of 20 people. 6-minute walk test (6-MWT) and Doppler echocardiography were performed in all patients. Besides myocardial tissue Doppler echocardiography and assessment of Nt-proBNP level were performed in 38 and 71 patients, respectively. Results. Dyspnea occurred in 90.7% of patients with various degrees of PH and 80.5% of patients with normal SPAP. Patients without PH and with PH I complained of palpitations, weakness, fatigue, and dizziness with similar frequency. Patients with PH I were comparable with ones of comparison group in 6-MWT distance that dramatically decreased in patients with PH II–III. Enlargement of the right atrium (RA) and/or right ventricular (RV) was observed in 76.7% of patients with PH I and 100% of patients with PH II–III. RV diastolic function abnormalities (E/A<1 and E/A>2) were detected in 19.4%, 16.7% and 61.5% of patients of comparison group, PH I and PH II–III patients, respectively. According to myocardial tissue Doppler echocardiography Em/Am<1 was observed in 8 (72.7%) patients of the comparison group and in 13 (76.4%) patients with PH. Nt-proB-NP level was 17.3 [2.3, 33.9] fmol/ml in PH I patients and 142.1 [62.1, 171.8] fmol/ml in PH II–III patients. Nt-proBNP level was 6.5 [3.1, 18.3] fmol/mL in patients of the comparison group, and it was higher than this in patients of the control group (3.5 [1.8, 7.5 fmol/ml]. Conclusion. Various indicators of heart remodeling and RV diastolic dysfunction were found in the majority of patients after pulmonary embolism, including those with nor- mal SPAP. Elevation of Nt-proBNP level adequately reflects the severity of RV dysfunction in CTEPH patients only in PH II–III. This marker has low diagnostic value in patients with- out CTEPH and PH I patients.


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Aim. To study the efficacy of cardiovascular non-invasive complex assessment and pre-operative preparation in hypertensive patients needed in surgical treatment of urology dis- eases.
Material and methods. Males (n=883), aged 40 to 80 years were included into the study. The main group consisted of patients that underwent laparotomic nephrectomy (LTN group; n=96) and patients who underwent laparoscopic nephrectomy (LSN group; n=53). Dynamics of ambulatory blood pressure monitoring (ABPM) data was analyzed in these groups in the immediate postoperative period. The efficacy of a package of non-invasive methods for cardiovascular system assessment was studied. ABPM was performed after nephrectomy (2-nd and 10-th days after surgery) in patients with complaints of vertigo episodes or intense general weakness to correct treatment.
Results. In LTN group hypotension episodes or blood pressure (BP) elevations were observed in 20 (20.8%) and 22 (22.9%) patients, respectively, on the 2-nd day after the operation. These complications required antihypertensive treatment correction. Patients with hypotension episodes were significantly older than patients with BP elevation and had significantly lower levels of 24-hour systolic BP, night diastolic BP and minimal night systolic BP. Re-adjustment of antihypertensive treatment on the 10-th postoperative day was required to 2 (10%) patients with hypotension episodes and to 1 (4.5%) patient with BP elevation. Correction of antihypertensive therapy was required to all patients in LSN group on the day 2, and to 32 (60.4%) patients on the 10-th day after the operation. Reduction in the incidence of complications (from 1.2% in 2009 to 0.3% in 2011, p<0.001) was observed during the application of cardiovascular non-invasive complex assessment and preoperative preparation in hypertensive patients.
Conclusion. The elaborated management algorithm for patients with concomitant hypertension is recommended to reduce the cardiovascular complications in the early postoperative period.


274-279 733
A new method of non-drug treatment of resistant hypertension – renal denervation is considered. General information about resistant hypertension, method of renal denervation, the results of clinical studies on efficacy and safety, as well as own clinical case are presented.


280-286 901
Tobacco smoking is a serious public health issue in Russia and one of the major risk factors of cardiorespiratory diseases. Smoking cessation is the most cost-effective measure for prevention of cardiovascular and respiratory diseases and for reduction in risk of death from these diseases. Helping the patients to quit smoking is difficult because of the nicotine addiction that most of them face. Nicotine replacement therapy (NRT) is used to reduce the tobacco dependence and withdrawal symptoms while quitting smoking and ease the transition from cigarette smoking to complete abstinence. NRT doubles the chances of smokers for quitting. Among modern pharmacotherapy approaches for smoking cessation NRT is a method of choice in cardiovascular and respiratory patients due to proven safety. NRT with a combination of slowand long-acting drugs with rapid-acting ones is more effective than NRT with a single type of drugs and helps to overcome the withdrawal symptoms and withstand tobacco dependence in a longer run. NRT may be successfully used as a pharmaceutical aid for patients with tobacco dependence in the hospitals when those will adopt the smoke-free hospitals status under the new Federal “antitobacco” law.
287-291 918
Epicardial fat is hormonally active tissue and has a direct impact on the myocardium state and coronary blood flow. The relationship of epicardial fat size and waist circumference with different clinical and metabolic parameters and coronary atherosclerosis severity in patients with ischemic heart disease is discussed.
292-300 734
Data on the problem of thromboembolic complications in non-valvular atrial fibrillation are presented. Peculiarities of anticoagulant therapy to prevent thromboembolic complications, the difficulties in drug choice and dosage adjustment are also discussed.


301-305 856
Low dose aspirin reduces the secondary incidence of myocardial infarction and stroke. Drug resistance to aspirin might result in treatment failure. Despite this concern, no clear definition of aspirin resistance has emerged, and estimates of its incidence have varied remarkably. Researchers from university of Pennsylvania (Philadelphia, the USA), led by Dr. Tilo Grosser, aimed to determine the specific phenotype of true pharmacological resistance to aspirin — such as might be explained by genetic causes. However the study failed to identify a single case of true drug resistance. Pseudoresistance, reflecting delayed and reduced drug absorption, complicates enteric coated but not immediate release aspirin administration.
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Besides hypolipidemic effect statins demonstrate some not-lipid (pleotropic) ones. Special attention has been paying to statin inducing reduction in bacterial infections incidence and severity, and pneumonia particularly. Results of the large studies on statin influence on infectious disease are presented.
311-315 3054
Interval QT prolongation is a predictor of the life-threatening cardiac arrhythmias — polymorphic ventricular tachycardia (torsade de pointes). Long QT syndrome may be congenital or acquired. It is known that a wide range of both antiarrhythmic and non-cardiac medications might lead to QT interval prolongation. List of drugs that cause QT prolongation is constantly growing and being updated. The review contains current data on the clinical significance of the control of QT interval duration within drug therapy. Clinical conditions associated with an increased risk of QT interval prolongation are described. Drugs that can induce QT prolongation are also discussed.
316-322 739
Disorders of intermediary metabolism in the glycolysis cycles and fatty acids oxidation play a major role in heart and brain lesions of vascular origin. Features of the free-radical processes in various forms of vascular disease are presented. Differences within the free-radical processes reflecting the severity of tissue energy deficit are shown in stroke patients with concomitant ischemic heart disease, atrial fibrillation, and diabetes mellitus. Various aspects of the treatment of patients with vascular comorbidity are presented with the focus on correction of intermediary metabolism disorders. Complex energy correcting therapy including beta-oxidation blocker (meldonium) is discussed.


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