Rational Pharmacotherapy in Cardiology

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Vol 8, No 5 (2012)
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626-635 781

Aim. To compare antihypertensive and metabolic effects as well as influence on erectile function (EF) of long-term treatment with carvedilol or bisoprolol in patients with arterial hypertension (HT) of 1-2 degree and overweight/obesity. Material and methods. A total of 105 patients were enrolled into randomized, an open-label comparative stepped trial. The patients were randomized into two groups: the group 1 (n=53) started treatment with carvedilol 25 mg daily and the group 2 (n=52) – with bisoprolol 5 mg daily. If the effect was insufficient a dose of a beta-blocker was doubled, then amlodipine was added in the dose of 5 mg daily with its further increase if necessary or indapamide 1.5 mg daily addition. The follow-up for each patient was 24 weeks. At the start and then 12 and 24 weeks later the frequency of target blood pressure (BP) achievement, body mass index, biochemical indices, ECG and treatment safety were evaluated. Besides, the International Index of EF (IIEF) was calculated with the special questionnaire. Results. The effect of the treatment on BP , body mass index, biochemical parameters, indices of insulin resistance and treatment safety were presented in the first part of the article [1]. IIEF showed increase in the group 1 as compared with both baseline and its state after 12 weeks of the treatment [+2.4±5.0 (p=0.002) for all items of EF questionnaire and +0.67±2.3 (р<0.05) for the 1-5,15 items of EF questionnaire]. Patients of the group 2 showed reduction in IIEF from 12 to 24 weeks of the treatment [-1.8±7.9 (р<0.01) for all items of EF questionnaire and - 0.73±2.7 (р<0.05) for the 1-5,15 items of EF questionnaire]. There were no differences in frequency and severity of adverse events between groups. Conclusion. At similar antihypertensive efficacy , carvedilol, in contrast to bisoprolol, had not only beneficial metabolic effects, but in long-term treatment was able to improve EF in patients with HT and abdominal obesity.

636-646 522

Aim. To study relationship between heart rate (HR) and traditional risk factors for cardiovascular diseases (TRF for CVD), subclinical structural and functional changes in the heart and vessels, as well as the activity and severity of rheumatoid inflammation in women with rheumatoid arthritis (RA). Material and methods. A total of 291 female patients less than 60 years of age with a definite diagnosis of RA were examined. The control group consisted of 125 women without rheumatic diseases. Aside from clinical symptoms, activity and severity level of RA, the presence of main TRF for CVD were assessed, 24 h Holter ECG monitoring (24-h ECG), duplex scanning of common carotid arteries, transthoracic echocardiography were performed and the serum levels of inflammatory markers were determined.  Results. RA patients compared with the control group women had higher values of minimum (52.3±0.4 vs 47.5±0.4; p<0.001) and mean (78.5±0.5 vs 75.5±0.5; p<0.001) HR according to 24-h ECG, after adjustment for main TRF for CVD (age, arterial hypertension, menopause, levels of total cholesterol, triglycerides, high density lipoprotein cholesterol). Accelerated HR in RA directly correlated with an increased joint functional disability index - HAQ, RA severity index, the level of inflammatory markers and administration of leflunomide after adjustment for age (р<0.05). Patients with HR≥86 beats per minute compared with RA patients with values of HR≤71 beats per min had lower total cholesterol (5.84±0.13 vs 5.11±0.17; p=0.001) and low density lipoprotein cholesterol levels (4.06±0.13 vs 3.28±0.18; p=0.001), longer duration, higher activity (Visual Analog Pain Scale, DAS28, extra-articular manifestations of RA, concentration of proinflammatory markers) and severity level of RA (severity index, HAQ, radiological stage III/IV), as well as  higher percentage of left ventricular diastolic dysfunction (LVDD) after adjustment for age. Conclusion. According to 24-h ECG, an increase in mean HR values in women with RA is associated with activity , severity of rheumatoid inflammation and LVDD. Prospective studies are needed to determine the role of accelerated HR as a risk factor for development of CVD and the feasibility of preventive measures creation aimed to lower HR to prevent cardiovascular events in RA.

647-654 588

Aim. To identify the most promising epitopes that simulate various sites β1-adrenergic and M2-cholinergic receptors, and to evaluate their possible contribution to the development and maintenance of cardiac arrhythmias, particularly idiopathic ventricular arrhythmia. Material and methods. Patients with ventricular arrhythmias without organic cardiovascular disease (the study group; n=70) were included in the study. The control group consisted of 20 healthy volunteers. Evaluation of levels of antibodies to antigenic determinants, modeling various sites β1-adrenergic and M2-cholinergic performed in all patients. Causal treatment with clarithromycin and valacyclovir performed in part of patients. Results. Antibodies to different peptide sequences of β1-adrenergic and M2-cholinergic receptors have been identified in 25% of main group patients. A direct correlation between the frequency of episodes of ventricular tachycardia and IgG levels to MRI-MRIV (p=0.02) revealed. Increase in titre of antibodies to β1-adrenoceptors, to a peptide sequence β8 (p=0.02), and lower titers of antibodies to the M2 acetylcholine receptor — chimera MRI-MRIV IgM (p=0.06) and ARI-MRIV IgM (p=0.07) were observed when assessing the efficacy of the therapy in the causal dynamics in the group of "untreated" patients. IgG titer reduction of ARI-MRIV (p=0.02), which is 4 times out of 10 with reduction of ventricular ectopic activity , recorded after valacyclovir therapy. Clarithromycin therapy on the level of antibodies exerted no significant effect. Conclusion. Possible involvement of antibodies to β1-adrenoceptor and M2-cholinergic receptors in the development of idiopathic ventricular arrhythmias demonstrated. The relationship between the frequency of episodes of ventricular tachycardia and levels of antibody titers to M2-cholinergic receptors found. Attempt of causal treatment, depending on the possible mechanisms of the autoimmune process is executed. Further studies to confirm or refute the results to the larger sample of patients are needed.

655-660 463

Aim. To identify possible predictors of atrial fibrillation (AF) recurrence in 6-month prophylactic propafenone therapy. Material and methods. Patients (n=63; aged 52.2±12.6 years; 25.4% women) with frequent AF recurrences who restored sinus rhythm with propafenone, were included into the study. Paroxysmal AF was observed in 84.1% of patients, and persistent AF — in 15.9% of patients. ECG, transthoracic echocardiography , chest radiography with the calculation of cardio-thoracic index (CTI) was performed at baseline. All patients received rpropafenone therapy (450–600 mg/day) during 6 months after sinus rhythm conversion. ECG and 24-hours ECG monitoring were performed in 1, 3 and 6 months of the therapy. Patients with 70–100% reduction in AF recurrence rate were included into the 1-st group, and patients with <70% reduction – into the 2-nd group. Results. 92%, 88.5% and 78% of patients were included into the group 1 after 1, 3 and 6 months of follow up, respectively. AF recurrences were observed 4.5, 3.8, and 1.7 times more often in women than these in men after 1, 3 and 6 months, respectively , (p>0.05). Mean age of patients in the group 2 was significantly older than this in patients of the group 1 (p<0.05). CTI, left atrium size and volume, interventricular septum thickness (IVST) were significantly larger in group 2. Myocardium mass of the left ventricle (MMLV) after 6 months of therapy was larger by 13.9% in patients of the group 2 vs this in patients of the group 1 (p<0.05). Conclusion. Insufficient preventive effect of propafenone was observed in 8%, 11.5% and 22% of patients in 1, 3 and 6 months of the follow-up, respectively. Propafenone prophylactic efficacy was slightly higher in men and younger patients. Patients with poor preventive effect of propafenone had a significantly larger baseline CTI, size and volume of the left atrium, IVST, and MMLV.

661-666 525

Aim. To assess the changes in blood pressure (BP) circadian profile and variability in patients with chronic heart failure (CHF) of ischemic etiology and arterial hypertension (HT) due to the complex therapy including ivabradine. Material and methods. Patients (n=90) with CHF class II–III NYHA associated with stable angina II-III class and HT were examined. The patients were randomized into 3 groups depending on received drugs: perindopril and ivabradine - group 1; perindopril, bisoprolol and ivabradine - group 2; perindopril and bisoprolol - group 3. The duration of therapy was 6 months. Ambulatory BP monitoring (ABPM) was assessed at baseline and after treatment. Results. More significant reduction in average 24-hours systolic BP was found in groups 1 and 2 compared to group 3 (Δ%: -19.4±0,4; -21.1±0.4 and -11.8±0.6, respectively) as well as diastolic BP (Δ%: -10.6±0.6; -12.9±0.4 and -4,3±0.3, respectively) and other ABPM indicators. Improvement of BP circadian rhythm was found due to increase in the number of «Dipper» patients (p=0.016). More significant reduction in average daily and night systolic and diastolic BP (p=0.001), as well as daily and night BP variability (p=0.001) was also found in patients of group 2 compared to these of group 1. Conclusion. Moderate antihypertensive effect (in respect of both diastolic and systolic BP) was shown when ivabradine was included into the complex therapy of patients with ischemic CHF and HT. The effect was more pronounced when ivabradine was combined with perindopril and bisoprolol. This was accompanied by reduction in high BP daily variability and improvement of the BP circadian rhythm.


667-674 587

Aim. To evaluate the efficacy of long-term combined antihypertensive therapy (AHT) based on renin-angiotensin-aldosterone system (RAAS) blockers, indapamide and calcium channel blocker (CCB) in hypertensive patients with diabetes mellitus (DM) in accordance with target blood pressure (BP) <130/80 mm Hg achievement rate, dynamics of 24-hour BP profile, metabolic indices, and local stiffness of the main arteries. Besides, to study the effects of the CCB addition to dual therapy on these parameters. Material and methods. Patients (16 men, 31 women, 57.2±6.6 years old) with arterial hypertension degrees 1–3 and mild to moderate DM type 2 were included into the study. The patients were treated with perindopril (5–10 mg/day) or valsartan (80–160 mg/day) in combination with indapamide SR (1.5 mg/day) and amlodipine (5–10 mg/day). Examination included office BP measurement and ambulatory BP monitoring (ABPM), common carotid arteries sonarography , evaluation of serum levels of potassium, creatinine, uric acid, glucose metabolism and lipid profile parameters, calculation of insulin resistance index (HOMA) at baseline and after 30–32 weeks of treatment. Results. Target BP was achieved in 86.7% of patients. Evenly reduction of day and night BP without reflex tachycardia and hypotension episodes was observed. Office BP decreased from 149.5±12.0/90.0±8.3 to 125.0±7.6/76.8±4.9 mm Hg (p<0.05) and average daily BP (ABPM) decreased to 120.1±10.0/71.7±6.9 mmHg. Three drugs were needed to achieve target BP in baseline systolic BP >150 mm Hg (office) or >134 mmHg (ABPM). Marked beneficial effect on the morphological and functional characteristics of the vascular wall and its elastic properties, improvement of glycemic control, tissue insulin sensitivity and lipids profile were found. These effects were associated mainly with amlodipine inclusion into the therapy. Conclusion. The combined AHT based on RAAS blockers, indapamide SR and CCB provides achievement of target BP in the most of hypertensive patients with DM and accompanied by positive changes in vascular remodeling and metabolism.


675-680 3638

Aim. Тo evaluate compliance of ongoing antithrombotic therapy (ATT) in various forms of atrial fibrillation (AF) with the risk level of thromboembolic complications (TEC), calculated with the СHADS2 and CHA2DS2–VASc scales in real clinical practice. Material and methods. A retrospective study of hospital records of 308 in-patients admitted to the cardiology departments of two multidisciplinary hospitals during the year because of nonvalvular AF . Risk of thromboembolic complications was estimated with the CHADS2 and CHA2DS2–VASc scales and appointed ATT was analyzed. Results. Patients with high risk of TEC were predominated in the study population: 77.6% and 91.9% according to CHADS2 and CHA2DS2–VASc scales, respectively. Moderate risk was found in  17.6%  and  6.1%  of  patients  according  to  CHADS2 and  CHA2DS2–VASc  scales,  respectively.  Only  32.2%  and  28.6%  28.6%  of  patients  at  high  risk  according  to  CHADS2 and  CHA2DS2–VASc scales, respectively received warfarin in hospital. All patients with permanent AF in this sample had a high risk of TEC according to the both scales. In the group of paroxysmal/persistent AF the high, moderate and low risk of TEC was identified in 87%, 9.9%, and 3.1% of patients, respectively , according to CHA2DS2–VASc scale and in 64.25%, 28.5% and 7.5% of patients, respectively , according to CHADS2 scale. Difference in high-risk patient rate was not significant among patients with permanent AF . In high risk group contraindications for receiving indirect anticoagulants were more frequent in the group with permanent AF (OR 3.1; 95% CI 0.88–10.7; p>0,05). The probability of warfarin prescription in patients with permanent AF was higher than in patients with paroxysmal or persistent AF (OR 1.98, 95% CI 1,18-3,31), and probability of aspirin prescription was lower (OR 0.82; 95% CI 0,51-1,32; p>0,05).  Conclusion. In real clinical practice oral anticoagulants are prescribed insufficiently in patients at high risk. Usage of CHA2DS2–VASc scale compared with usage of CHADS2 scale, leads to significant increase in the proportion of patients at high risk due to reduction in the proportion of patients with moderate risk in persistent or permanent AF . Usage of CHADS2 scale can lead to an underestimation of the TEC risk in patients with persistent or permanent AF .

681-684 463

Aim. To assess the patients’ pharmacotherapy preceding the acute myocardial infarction (AMI) and to assess the effects of this therapy on hospital mortality. Material and methods. 1133 patients were enrolled into the LIS AMI register . All these patients experienced AMI leading to hospital admitting in the territory of one of the districts of the Moscow Region during 3 years. The pharmacotherapy that patients received before AMI was analyzed as well as the influence of different drugs on the hospital mortality risk. Results. 172 of 1133 patients (15.2%) died in hospital. Before admission 21.4% of patients received β-blockers, 35.3% — ACE inhibitors, 15.7% — antiplatelet drugs, 1.9% — statins. Reduction in the hospital mortality rate was shown for β-blockers [relative risk (RR)=0.542, confidence interval (CI) =0.357–0.824] and ACE inhibitors (RR=0.710, CI=0.512–0.986). Conclusion. A significant part of patients with high risk of AMI does not receive drugs with proven positive effect on the life prognosis.

685-690 550

Aim. To evaluate the clinical results of thrombolytic therapy with thrombolytics (alteplase, tenecteplase) in patients with ST segment elevation myocardial infarction (STEMI). Material and methods. Patients with STEMI (n=181) included in the study were split into two groups depending on the thrombolytic agent: patients treated with alteplase - group 1 (n=78); patients treated with tenecteplase — group 2 (n=52). Patients with STEMI who had no thrombolysis due to late treatment-seeking or the presence of contraindications were included into the group 3 (n=51). Thrombolysis took place both in pre-hospital and in-hospital period. Time before the thrombolysis, STEMI clinical course, mortality , and complications were analyzed. Results. The average time pain-thrombolysis was 2.7±0.22 hours. High efficacy of both thrombolytic drugs was proved in the most of patients. Mortality in patients received thrombolysis was 6.4–7.7%; this in patients without thrombolytic therapy — 24%. Thrombolysis performed in the first 3 hours after STEMI onset reduced mortality to 3.4%. No one intracranial hemorrhage or allergic reaction was registered. Conclusion. Thrombolytic therapy with alteplase and tenecteplase in patients with STEMI in the real clinical practice was high efficient, reduced hospital mortality and induced a few adverse reactions.


691-693 634

Assessment of lipid-lowering effect of rosuvastatin is presented, as well as the main results of the study of rosuvastatin therapy efficacy , in comparison with other statins, received in controlled clinical trials of the GALAXY program: COMETS, LUNAR, MERCURY-I, SOLAR, STELLAR.

694-698 409

The main symptoms and clinical types of long QT syndrome are described. Molecular genetic diagnostics and updated approaches to the management of patients with long QT syndrome are

699-702 430

Highly selective β-adrenoblockers (β-AB) are used in pregnant women with cardiovascular diseases (arterial hypertension, arrhythmia, Marfan syndrome, hypertrophic cardiomyopathy). β-AB fall into the category C according to safety classification of Food and Drug Administration (US FDA). Their prescription in different clinical situations meets the principle of "risk–benefit". Fetus and newborn status should be monitored because β-AB can cause bradycardia, hypoglycemia, apnea and metabolic disorders. The risk of these side effects is extremely low, while β-AB clinical efficacy is high.


703-707 1307

Results of experimental and clinical studies devoted to urapidil combining central antihypertensive effect with peripheral vasodilatation are discussed. Scope of urapidil application is described; its good tolerability and safety are highlighted. Urapidil mode of application in different clinical situations accompanying by acute increase in blood pressure is specified.

708-716 586

Use of acetylsalicylic acid (ASA) in cardiology practice is presented. ASA modes of action and the main indications are discussed. ASA use for primary cardiovascular diseases prevention and its possible side effects are considered especially. Peculiarities of ASA use in specific clinical situations, and some pleiotropic effects are also presented.


717-720 442

Aim. To study the role of hormonal and metabolic changes specific to myocardial infarction in the development of inflammatory reactions in the experimental non-coronarogenic myocardial damage. Material and methods. Wistar male rats weighing 180–220 g (n=80) were used in the study. Metabolic myocardial infarction in intact rats and rats with alloxan diabetes was induced by epinephrine injected subcutaneously as single dose or daily (7 days). Myocardial infarction was verified by ECG analysis, and by histological control. Nitroblue tetrazolium test (NBT-test) both spontaneous and zymosan induced NBT-test was used to determine the oxygen-dependent functional activity of neutrophils and their biocidal reserve. Determination of cationic proteins in neutrophils of peripheral blood was performed using lysosomal-cationic test. Results. Increase in oxygen-dependent neutrophil biocidal activity was found as well as reduction in biocidal reserves. Indicators of zymosan induced NBT-test raised according to aggravation of hormonal changes much slower: alloxan increased them by 10% only , epinephrine single dose — by 35%, long-term epinephrine administration simultaneously with alloxan — by 54%. At the same time oxygen-independent neutrophil activity determined by intra-neutrophil cationic proteins level was significantly reduced. Blood levels of pro-inflammatory cytokines raised according to progression of the changes in myocardium: tumor necrosis factor-α (from 5.5±0.03 to 12.6±1.23 pg/ml) and interleukin-1β (from 6.0±0.18 to 11.1±0.78 pg/ml). Conclusion. Experimental model of hormonal changes specific to myocardial infarction detected a relationship between inflammatory reactions accompanying myocardial damage and increased catecholamine production.


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