Rational Pharmacotherapy in Cardiology

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Vol 3, No 2 (2007)
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6-10 2350

Aim. To evaluate the incidence of cardiac rupture (CR) in patients with acute myocardial infarction (MI) as well as predisposing factors during 15-year follow-up.

Material and methods. 1453 patients with acute MI who were admitted to Krasnoyarsk cardiological center during 1989, 1993 and 2003 years were studied. All patients were divided into three groups: group I - 447 patients, who were on treatment in 1989, group II - 475 patients of 1993, and group III – 531 patients of 2003. There were no differences in groups on patient sex, location and depth of MI, previous MI, arrhythmias, heart failure and diabetes mellitus.

Results. CR was found in 18 of 447 patients (4%) of group I (1989), in 16 of 475 patients (3,4%) of group II (1993) and in 10 of 531 patients (1,9%) of group 3 (2003), (p1,3 <0,05). Incidence of CR significantly decreased from 1989 to 2003 in female patients (7,2%; 5,7% and 1,6% in 1989, 1993 and 2003, respectively; p1,3 < 0,01, p2,3 < 0,05). Incidence of CR in male patients didn’t changed (2,5%, 1,8% and 2,1%, respectively). The average blood pressure (BP) during the first day of MI in female patients was higher than this in male ones in 1989 and 1993. There were no significant differences in BP between women and men in 2003. Heart rate (HR) during the first day of MI in female patients was higher than this in male patients in 1989. However in 1993 and 2003 there were no differences in HR between women and men. MI therapy more often included betablockers, angiotensin converting enzyme inhibitors, intravenous nitrates, statins, thrombolythics and anticoagulants in 2003 than in 1989 and 1993.

Conclusion. Effective BP and HR control is the most effective way to prevent CR in patients with MI.


11-15 4010

Aim. To evaluate antianginal and antiischemic efficiency of nebivolol in patients with stable angina pectoris.

Material and methods. 100 patients with ischemic heart disease showing stable exertional angina pectoris and having no contraindications to beta-blockers were studied. After 5-7 days of control period 50 randomly selected patients began to take nebivolol in initial dose of 5mg once daily and 50 patients started to take metoprolol in initial dose of 50 mg twice daily. Duration of treatment was 8 weeks. Efficiency of treatment was assessed according to the results of control treadmill assessment and control daily ECG monitoring.

Results. 56-day therapy with nebivolol at a dose of 7,5 mg per day results in increase in duration of treadmill test before angina or ST depression (p<0.05). Antianginal and antiischemic effect of nebivolol 7.5 mg once daily is rather similar with that of metoprolol in average daily dose of 175 mg. Nebivolol compared to metoprolol significantly (p<0.05) more effectively reduces the number of silent myocardial ischemia.

Conclusion. Nebivolol is an efficient antianginal and antiischemic drug for patients with stable exertional angina pectoris.

16-19 1608

Aim. To estimate the role of immuno-inflammatory response in developing of angina pectoris in patients with ischemic heart disease (IHD).

Material and methods: The study included 83 patients with IHD and angina pectoris of functional class (FC) II (30 patients), III (27 patients) and IV (26 patients). The control group included 25 healthy persons. Bicycle burden test, daily ECG monitoring and echocardiography were used to verify of IHD. Levels of С-reactive protein (CRP), pro-inflammatory cytokines: interleukin-1β, interleukin-6 (IL-1β, IL-6) and tumor necrosis factor alpha (TNF-α) were examined by immunoenzyme method. Levels of anti-inflammatory cytokines were also defined: interleukin-4 and interleukin-10 (IL-4, IL-10).

Results. Increased levels of IL-4 and IL-10 with normal CRP and pro-inflammatory cytokine levels were observed in patients with angina of FC-II. Angina of FC-III was associated with a moderate increase in CRP level and normal levels of IL-4 and IL-10. The maximal levels of CRP and pro-inflammatory cytokines as well as minimal levels of anti-inflammatory cytokines were observed in patients with FC-IV angina pectoris.

Conclusion. The immuno-inflammatory response depends on angina pectoris severity in patients with IHD. Severe angina pectoris is accompanied by raised expression of pro-inflammatory cytokines and deficiency of anti-inflammatory cytokines.

20-25 557

Aim. To evaluate antianginal and antiischemic activity of molsidomine (Corvaton) in stable angina pectoris of II-III functional class (FC).

Material and methods. 45 patients with II FC (31 persons) and III FC of angina (14 persons) were included into the study. All patients took molsidomine in individual doses during 3 months. Antianginal and antiischemic activity of molsidomine was estimated by veloergometric tests.

Results. Molsidomine therapy resulted in disappearance of angina pectoris in 41, 7% of patients with stable angina of II-III FC and reduction of ST depression.

Conclusion. Molsidomine is an effective antianginal and antiischemic medicine in patients with stable angina of II-III FC and provides the stable effect during long-term usage.

26-30 607

Aim. To develop a protocol for comparison of efficacy and safety of original drugs with generic ones and to apply this protocol for comparison of generic indapamide (Indap) with original indapamide in two presentations: short acting (Arifon) and long acting (Arifon Retard).

Materials and methods: 64 patients with arterial hypertension of 1-2 degree took part in open cross-over randomized study. All patients were treated with Indap as well as with Arifon (half of patients) or Arifon Retard (another half) for comparison. Each kind of therapy lasted for 6 weeks; sequence of drug administration was randomized. The effect of treatment was assessed by resting blood pressure (BP) dynamics. If antihypertensive effect was not sufficient after 3 weeks of treatment, lisinopryl (Dapril) 10 mg/d was added.

Results. There were no differences between basic clinical characteristics in groups of patients initially treated with different indapamide medications. Systolic and diastolic BP significantly reduced after 3 weeks of treatment without difference between tested indapamide medications. Combined therapy led to additional decrease in BP without significant difference between the patients groups. There was no significant difference in groups on the rates of side effects caused by therapy with tested indapamide medications.

Conclusion. The proposed protocol of study showed that there were no significant differences in efficacy and safety of two presentations of original indapamide and tested generic indapamide in hypertension treatment.

31-37 504

Aim. To study prevalence of essential hypertension (HT) and chronic obstructive bronchitis (COB) among Rostov-on-Don population, to assess influence of ecological stress on HT and COB development and to find the ways to improve therapy of combined pathology.

Material and methods. Single-stage epidemiologic study of Rostov-on-Don population was carried out. The study included questionnaire to reveal main risk factors of chronic noninfectious diseases, a number of laboratory and instrumental indices.

Results. Prevalence of HT and COB is significantly higher in patients, living in ecologically unfavorable districts. Rigidity and stretch ability of vascular wall influence the course and development of HT as well as atrial natriuretic factor. Carbonic anhydrase inhibitor, acetazolamide, when is added to standard therapy increases in its efficacy in blood pressure control, decrease in blood pressure in pulmonary artery and correction of disturbed acidbase balance in patients with HT combined with COB.

Conclusion. The connection between unfavorable ecology and HT and COB development is demonstrated. Adjuvant therapy with acetazolamide is proposed to increase in efficacy of HT and COB standard therapy.
38-42 487

Aim. To increase in efficacy of antihypertensive therapy in patients with refractory arterial hypertension (HT).

Material and methods. Patients with refractory HT were revealed during first month of program. The causes of refractory HT were analyzed. Combined antihypertensive therapy was prescribed to reach target level of blood pressure (BP). This therapy lasted 24 weeks and included angiotensin converting enzyme (ACE) inhibitor, thiazid diuretic (indapamide) and dihydropyridine calcium antagonist (nifedipine XL).

Results. 200 patients with refractory HT were revealed. True refractory HT took place in 59,9% of patients and pseudo refractory HT – in 40,1% of patients. Lack of diuretics or combined antihypertensive therapy were the main reason of insufficient BP control. Proposed 3-drugs therapy resulted in reduction of systolic BP from 190 to 132 Hg mm and diastolic BP from 104 to 81 Hg mm. Target level of BP was reached in 94% patients. There were no side effects which demanded to stop therapy.

Conclusion. High incidence of pseudorefractory HT (40,1%) is revealed. Significant prevalence of renal disturbances especially chronic interstitial inflammatory could be responsible for refractory HT development. Use of 3-drugs therapy (ACE inhibitor, indapamide and nifedipine XL) provides effective control of BP in refractory and pseudorefractory HT.

43-47 2927

Aim. To evaluate the effect of imidasoline agonist, rilmenidine (Albarel), on 24-hour blood pressure (BP) profile and autonomic regulation of cardiovascular system in young patients with arterial hypertension (HT) and exogenous constitutional obesity (ECO).

Material and methods. The study included 80 men aged 18-32 ( average age 20,5 years), including 34 patients with HT and normal body weight, 36 patients with HT and ECO, 10 healthy men as a control group. All hypertensive patients were treated with rilmenidine 1-2 mg daily during 12 weeks. BP 24-hour profile and heart rate variability (HRV) were estimated before and after therapy.

Results. Rilmenidine monotherapy resulted in significant reduction in average 24-hour, day-time and night-time BP as well as indices of BP loading in both groups. Indices of HRV proved the initial sympathetic overdrive among hypertensive patients especially among those with ECO. This sympathetic overdrive significantly reduced after 12 weeks of therapy.

Conclusion. Rilmenidine effectively controls BP and reduces sympathetic system overdrive in young hypertensive patients with ECO.

48-52 1641

Aim. To evaluate intensity of endothelial dysfunction, processes of apoptosis, state of central and peripheral hemodynamics and to evaluate how these characteristics are influenced by angiotensin II receptors antagonists (ARA II) – candesartan (Atacand) and losartan (Cosaar) in patients with chronic cor pulmonale (CCP) at different stages of disease.

Material and methods. 100 patients with chronic obstructive pulmonary disease (COPD), complicated by CCP were included into the study. Caspase activity as apoptosis induction marker, von Willebrand factor, production of nitric oxide in blood plasma and condensate of breathing out air were assessed. 70 patients received ARA II (50 patients – candesartan 4-8 mg daily, 20 patients – losartan 50-100 mg daily), 30 patients received neither ARA II nor angiotensin converting enzyme inhibitors (ACEI).

Results. Significant increase in intensity of endothelial dysfunction and activation of apoptosis processes were registered according to growth of CCP severity. After 6 months of therapy von Willebrand factor decreased by 25,2% and 27,7% in candesartan and losartan groups respectively (p<0.01 for both groups). In the control group only 13.2% of von Willebrand factor reduction was seen.

Conclusion. ARA II added to common therapy of COPD complicated by CCP improves functional state of endothelium restricting hyperproduction of nitric oxide and its toxic effects and slowing down apoptotic cell death.


53-58 554

The review is devoted to the modern data about mechanisms of cardiovascular dysfunction in patients suffering diabetes mellitus type 2, especially to the role of oxidative stress. It is determined that oxidative stress is involved in the development of myocardial ischemia, reperfusion-syndrome, endothelial dysfunction and atherogenesis. There are data that angiotensin converting enzyme inhibitor, zofenopril, has both cardio- and vasoprotective activities as well as antioxidative effect. These features are rationales to use it in patients with ischemic heart disease and diabetes mellitus.

59-66 921

Indirect anticoagulants effectively prevent thromboembolic complications in patients with high risk of their development. It was proven in multicenter controlled studies. However in spite of efficient laboratory control of anticoagulant effect with the international normalized ratio, treatment with drugs of this group deals with high risk of bleeding including fatal one. Latest decade studies showed that efficacy and safety of indirect anticoagulants significantly depend on genetic factors in the form of polymorphisms of genes of their biotransformation (CYP2C9) and molecule-targets (VKORC1). This created basis for usage of pharmacogenetics approach for individual choice of indirect anticoagulant dose regime. However to use this approach in clinical practice physician needs to have algorithms for choosing of indirect anticoagulant dose regime according to pharmocogenetics test results. Analysis of these existing algorithms, their advantages and disadvantages are described in the review.


67-71 485

The efficacy of calcium antagonists widely used in cardiological practice is proved both by placebo-controlled studies and in comparative trials with end-point control. Calcium antagonists are the most effective vasoprotective medicines. In our study we had shown antihypertensive efficacy and ability to improve endothelium function of non-dihydropyridine calcium antagonist, diltiazem (Altiazem RR). Altiazem RR can be drug of choice in wide profile of patients with arterial hypertension, especially in those with concomitant metabolic abnormalities, diabetes mellitus and ischemic heart disease.


98-99 2228

Comments on Guidelines of American College of Cardiology, American Heart Association and European Society of Cardiology (2006) for the management of patients with atrial fibrillation.

100-101 347

Higher Certifying Commission News.

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