Rational Pharmacotherapy in Cardiology

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Vol 8, No 4 (2012)
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488-499 854

Aim. To compare antihypertensive and metabolic effects 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 open-label comparative stepped trial in two parallel groups. 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 in dose 1.5 mg daily. 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. Results. Significant distinctions in antihypertensive therapy effect between the groups were absent (ΔBP=-29.5±11.3/17.8±8.4 and -30.4±12.8/18.7±8 mm Hg for groups 1 and 2, respectively , p<0.001 for the both groups) as well as the necessity for additional therapy. All the patients completed the study had achieved target BP level. The patients of the both groups decreased body mass index after 6-month treatment (-0.57±1.1, p=0.001 and -0.53±0.8 kg/m2, p<0.001 for groups 1 and 2, respectively). Patients of the group 1 demonstrated significant reduction in fasting plasma glucose level (-0.45±1.2 mM/l, p=0.01), uric acid (-0.05±0.01 mM/l, p<0.001) and low-density lipoprotein cholesterol level (-0.28±0.9 mM/l, p<0.05) as well as a trend for HOMA index decrease. Serum creatinine level increased in patients of the group 2 (6.35±22.4 mcM/l, p=0.05) with no significant dynamics in metabolic indices. Glomerular filtration rate did not change significantly in the group 1, while there was significant decrease in the group 2 (Δ-3.8±15.2 ml/min/1,73m2, р=0.01). The groups did not differ in adverse events incidence and severity. Conclusion. The CABRIOLET study showed similar antihypertensive efficacy of carvedilol and bisoprolol in HT patients with abdominal obesity and confirmed favorable metabolic effects of long-term treatment with carvedilol, unlike bisoprolol.

500-508 473

Aim. To study the effect of treatment with inhaled nitric oxide (iNO) on the clinical status of patients with idiopathic pulmonary hypertension (IPH), and the profile of proinflammatory cytokines in peripheral blood. Material and methods. Patients with IPH (n=48) were included into the study. Evaluation of the IPH functional class (FC), the 6-minute walk test (6MWT) with the assessment of the Borg index, echocardiography , laboratory tests [blood count, evaluation of high-sensitivity C-reactive protein (hsCRP), interleukins (IL), interferon-γ (INFγ), tumor necrosis factor a (TNFa), macrophage inflammatory protein a (MIP1 a), soluble adhesion molecules (sICAM-1, sVCAM-1) in peripheral blood] were performed at baseline and on day 21 of iNO therapy course. The iNO course 40 ppm during 5 hours a day for 21 days was carried out additionally to the standard IPH therapy under the toxicity control by the PrinterNOx (England). Results. Increase in exercise tolerance, improvement of IPH FC (from 3.35±0.52 to 2.71±0.56; p=0.008), reduction in systolic pulmonary artery pressure (SPAP) by Doppler echocardiography (from 96.23±23.65 to 82.36±20.92 mmHg; p<0.05) were found in IPH patients as a result of iNo therapy. The significance of inflammation in IPH pathogenesis was confirmed due to assessment of the initial levels of proinflammatory cytokines. iNO therapy resulted in significant decrease in proinflammatory cytokines-IL-1β, IL-6, IL-8, TNFa levels. iNO induced significant dynamics of IL-1β and sVCAM in patients with IPH FC II. It reduced IL-8 and TNFa and increase INFγ (p<0.05) in patients with IPH FC III-IV. Changes in IL-1β and sVCAM levels (ΔIL-1β and ΔsVCAM) by the 21 day of iNO therapy in comparison with these at baseline correlated with ΔSPAP , and ΔIL-6 correlated with ΔFC and Δ6MWT distance (30.5 [21.0; 53.0] m; p<0.001). This allows considering these indicators as markers of iNO treatment efficacy. Conclusions. 21-day iNO therapy in IPH patients resulted in significant improvement of functional status, reduce SPAP and caused the positive dynamics of proinflammatory cytokines blood levels.

509-514 464

Aim. To study the effect of combined antihypertensive therapy on the basic parameters of the left ventricle (LV) myocardium structure and function in women with arterial hypertension (HT), metabolic syndrome (MS) and hypothyroidism. Material and methods. Women (n=196) with HT grade 2–3 and MS were included into the study. Standard clinical examination including an assessment of thyroid status, ambulatory blood pressure (BP) monitoring and echocardiography was performed at baseline and after 6 months. The patients were split into 3 groups: control (without hypothyroidism) with subclinical and manifested (symptomatic) hypothyroidism (SH and MH). Depending on baseline heart rate (HR) patients of each group received a combination of amlodipine+losartan (A+L) in HR <85/min or a combination of amlodipine+moxonidine (A+M) in) in HR ≥85/min. Results. The significant antihypertensive effect was found in patients of the control group due to both A+L and A+M combination (target BP was reached in 85.7 and 88.2%, respectively). In patients with hypothyroidism significant antihypertensive effects was observed only during A+M therapy (target BP in SH and MH was achieved in 82.8 and 82.4%, respectively). In the control group A+L and A+M combinations increased a number of patients with normal LV geometry (85.7 and 86.7, respectively) and diastolic function (78.6 and 80%, respectively). In hypothyroidism A+M therapy resulted in more prominent increase in a number of patients with normal LV geometry (75% in both SH and MH) and diastolic function (in SH and MH 83.3 и 85.7%, respectively) than these in A+L therapy (р<0.05). Conclusion. The combination of A+M has advantages over A+L combination in antihypertensive efficacy as well as in the effect on the structural and functional state of the LV myocardium in women with HT and MS associated with hypothyroidism.

515-520 494

Aim. To study the possibility of enhancing the antianginal effect of long-acting nitrates by their combination with trimetazidine in patients with stable angina. Material and methods. Patients with ischemic heart disease (IHD, stable angina; n=55) were included into the study. Patients were randomized to receive trimetazidine 35 mg 2 times a day (intervention group) or placebo (control group) in addition to standard therapy. A daily number of angina attacks, amount of short-acting nitroglycerin tablets consumed per week, exercise tolerance by the bicycle ergometry with the calculation of the threshold power and the work capacity were assessed at baseline and after 2 months of the drugs taking, as well as 2 months after the drugs withdrawal. Results. Significant reduction in nitroglycerin tablets consumption (1 month — by 61.8%, after 2 months — 72.5%, p<0.05) were found in the intervention group compared with the control group. Low intake of nitroglycerin compared with baseline (p<0.05) was maintained for 2 months after discontinuation of study drug. Significant increase in the threshold power (1 month — by 32.3%, after 2 months — 37.5%, p<0.05) was observed in the intervention group compared to baseline and with the control group. Conclusion. Trimetazidine in the treatment of stable angina has high clinical efficacy.


521-525 488

Aim. To identify the factors of the increasing the availability and effectiveness of pre-hospital thrombolytic therapy of patients with ST segment elevation acute coronary syndrome (STEACS). Material and methods. STEACS patients (n=70) were included in the study and stratified into two groups. Patients of the 1st group (n=30) received emergency medical assistance from the feldsher teams and patients of the 2nd group (n=40) — from the doctor teams. Expert estimation approach was used for the real practice assessment. Results. The hospital-matched diagnose rate was 97.5% in the doctor teams in comparison with 76.7% in feldsher teams (p<0.05). The efficiency of pre-hospital thrombolysis in 90 minutes after its beginning was 60.1% for the doctor teams versus 73.3% for the feldsher teams (p>0.05). The deviation from the standard operating procedure of the medical care for myocardial infarction patients was observed more often in the doctor teams in comparison with this in the feldsher teams. Time for the decision about pre-hospital thrombolysis start, the rate of unreasonable use or unreasonable refusal of thrombolysis did not differ significantly in feldsher and doctor teams. Conclusion. To increase the effectiveness of pre-hospital thrombolysis therapy it is necessary to follow strictly the standard of the medical care for patients with acute coronary syndrome. One of the main approaches to improve the availability of up to date medical care technologies in STEACS treatment is implementation of pre-hospital thrombolysis in practice of feldsher teams.


526-530 501

Aim. To assess effects of quinapril on the regulatory-adaptive status (RAS) in patients with chronic heart failure (CHF) NYHA class 1 and arterial hypertension (HT). Material and methods. Patients (n=49) with CHF NYHA class I and HT stage I–II (25 men and 24 women, aged 52.5±8.4 years) were included into an open noncomparative study. A cardio-respiratory synchronization (CRS) test, 6 minute walk test, treadmill test with evaluation of the maximal oxygen uptake during exercise, ambulatory blood pressure monitoring, echocardiography , determination of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) plasma level were performed at baseline and after 6 months of quinapril therapy. Results. The quinapril treatment (average daily dose 17.3±7.9 mg) improved myocardium structural and functional parameters, increased the exercise tolerance, reduced neurohumoral activity , improved the RAS according to CRS test: increase in synchronization range of cardiorespiratory cycles per minute from 8.0±2.1 to 11.0±2.5 (Δ27.3%; p<0.01), as well as RAS index from 52.6±7.8 to 89.7±8.9 (Δ41.4%; p<0.01), and decrease in the duration of CRS development at the minimal border of cardiac cycles from 15.5±3.5 to 12.9±2.8 (Δ15.8%; p<0.01). Conclusion. Quinapril has a positive effect on the RAS in patients with CHF NYHA class I and HT of stage I–II.


531-537 477

Alternative approaches to the use of two component antiplatelet therapy in patients with acute coronary syndrome are discussed. Reasons to the development and implementation of new, more powerful antiplatelet agents are considered. Besides the evidence base for the practical application of new antiplatelet agents is discussed, especially this for ticagrelor which is the first-line drug in acute coronary syndrome according to European clinical guidelines. Subjective limitations of ticagrelor use in clinical practice are discussed, as well as a basis for overcoming these limitations.

538-544 523

Early and aggressive treatment of patients with risk factors and clinically manifest cardiovascular diseases is one of the priorities of modern medicine. This therapy usually consists of several components according to multifactor origin of cardiovascular disease (CVD). Correction of lipid metabolism has become one of the strategic directions. First-line agents in the treatment of dyslipidemia in patients with CVD risk factors, of course, are statins. The results of multi-center studies showing the benefits of rosuvastatin in the prevention and treatment of cardiovascular diseases are presented.

545-553 638

Magnesium is a macronutrient that is needed for normal body functions. Magnesium deficiency resulting from the influence of exogenous and endogenous factors, is diagnosed by clinical manifestations, resembling the known disease. Magnesium deficiency corrected with the magnesium therapy. Studies show the effectiveness of magnesium orotate for many cardiovascular diseases.

554-560 705

Review is devoted to the role of modern beta-blocker nebivolol in the treatment of stable ischemic heart disease (IHD). The mode of nebivolol anti-ischemic activity is considered, as well as its use particularities in IHD patients with different concomitant diseases. Nebivolol effects are compared with these of other beta-blockers and other antianginal drugs in terms of angina symptoms reduction, quality of life improvement and decrease in cardiovascular complications risk.

561-568 453

Inhibitors of the renin-angiotensin-aldosterone system, statins, and possibly , ω-3 polyunsaturated fatty acids may influence the incidence of atrial fibrillation (AF), and can be used to prevent it. In recent medical literature, this approach is referred to as upstream treatment. The results of experiments and clinical studies show that the use of these drugs may be useful for AF primary prevention in certain categories of patients. Nevertheless, there are currently no sufficient evidences to justify these recommendations and apply them to a wider range of patients with AF risk factors. Thus, it is reasonable to continue studies on both primary and secondary AF prevention.

569-572 448

Up to date antithrombotic medications applied in patients with atrial fibrillation are discussed. Along with traditional drugs (acetylsalicylic acid, warfarin) rivaroxaban is specially considered
in terms of efficacy and safety of alone.


573-580 551

The results of recent trials on acetylsalicylic acid (ASA) efficacy are presented. Data potentially related to the possibility of ASA indications extension is discussed, in particular that referring to the cancer prevention. This ASA indication should be confirmed in additional studies.

581-586 553

Analysis of the current literature data on the use of warfarin in patients with cardioembolic stroke is presented. Cardioembolic stroke pathology and particularities of this condition therapy
with antithrombotic medications are shown in details. Possibility to apply thrombolysis during warfarin treatment and the use of anticoagulants after cardioembolic stroke is discussed.

587-594 771

Widespread use of antihypertensive and lipid-lowering agents in clinical practice determines the necessity of knowledge of their pleiotropic effects. Results of studies of the effect of cardiac drugs and, first of all beta-blockers, ACE inhibitors, diuretics, and statins on bone are presented. Mode of action on the bone mineral density , markers of bone turnover and ultimately impact on the incidence of fractures associated with osteoporosis are discussed. At the present time there are no sufficient evidences of positive effect of these medications on bone coming from randomized controlled trials. It is not possible to recommend discussed cardiovascular drugs for prevention of osteoporosis and fractures, as well as registration new indications for them. However , knowledge of additional effects on the bone metabolism in cardiovascular drugs, will allow doctors to choose optimal treatment of hypertension and lipid disorders, taking into account the state of bone tissue. At the same time it will also allow to prevent osteoporosis in patients having osteoporosis risk factors or initial signs of bone loss.



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ISSN 2225-3653 (Online)