The article is devoted to the diagnosis, treatment and secondary prevention of thromboembolism from position of different specialists – cardiologists, neurologists, angiosurgeons, pulmonologists. The possibilities of anticoagulant therapy in the treatment and prevention of thromboembolism are shown. The evidence base regarding usage of new oral anticoaguants in patients with pulmonary thromboembolism, ischemic stroke, deep vein thrombosis, often having concomitant pathology, such as atrial fibrillation or heart failure, is provided. The importance of the follow-up in patients with successfully treated thromboembolism is emphasized.
The article considers usage of the metabolic antianginal drug trimetazidine for treatment of patients with ischemic heart disease and angina pectoris. The results of the studies of trimetazidine in patients after coronary artery bypass grafting and percutaneous transluminal coronary angioplastics are presented. The usage of trimetazidine has perspective in patients with chronic heart failure, as well as after revascularization, being a potentially important direction for future studies.
The aim – to determine the influence of the systemic enzyme therapy on cardiovascular risk level, its relation to the intensity of systemic inflammation and traditional factors of atherogenesis.
Material and methods. The dynamics of the main cardio-vascular risk indexes in patients with osteoarthritis was investigated during 6 months on standard treatment (the control group) and in patients receiving the systemic enzyme therapy drug (the group of treatment).
Results. In patients of the control group, we noted the progressive increase of inflammation and oxidative stress indices, as well as further activation of angiotensin-converting enzyme. These changes were accompanied by proatherogenic changes of the lipid and glucose metabolism, atherogenic and immunogenic modification of the lipoprotein spectrum. In parallel generalized structural and functional remodeling of the arterial vascular wall and endothelial dysfunction was noted. Systemic enzyme therapy sharply inhibited systemic inflammation and oxidative stress in conjunction with restoration of the antioxidant plasma potential. It improved lipid spectrum, decreased hyperglycemia and lowered plasma HbA1c level. Metabolic parameters in patients with low residual inflammation were close to their normal value.
Conclusions. Apart from antiinflammatory action, systemic enzyme therapy in patients with osteoarthritis promotes decrease of cardiovascular risk factors, partially restores the structural and functional properties of the arterial vessels.
Combination treatments for hypertension most often include a renin-angiotensin-aldosterone system (RAAS) inhibitor. However, systolicblood pressure (SBP) remains difficult to control. Non-RAAS-inhibiting strategies such as calcium channel blocker/thiazide-like diuretic combinations may offer effective alternatives.
Material and methods. Hypertensive diabetic patients with microalbuminuria were included in this retrospective, post-hoc analysis of the Natrilix SR Versus Enalapril Study in Hypertensive Type 2 Diabetics With MicrOalbuminuRia (NESTOR) trial if they were uncontrolled on monotherapy (indapamide slow release (SR) 1.5 mg or enalapril 10 mg) and had been given add-on amlodipine 5 mg. Patients uncontrolled with monotherapy/amlodipine 5 mg were uptitrated to 10 mg.
Results. After 52 weeks, supine SBP/diastolic BP (DBP) decreased from baseline by 26±13/14±9 mm Hg in the indapamide SR/amlodipine group (n=135) and by 21±14/11±9 mmHg in the enalapril/amlodipine group (n=156) (P=0.006 for ΔSBP). In the amlodipine 10 mg subgroup, SBP/DBP decreased from baseline by 26±13/13±9 mmHg in the indapamide SR/amlodipine group (n=62) and by 20±13/12±8 mmHg in the enalapril/amlodipine group (n=77) (P=0.02 for ΔSBP). Treatment with indapamide SR/amlodipine was well tolerated. Few patients experienced edema, with no between-group differences. As expected with diuretics, slight changes in kalemia and in uricemia were observed in the indapamide SR/amlodipine group. Changes in fasting glucose, lipids, natremia, and creatinine clearance were similar between groups.
Conclusions. Indapamide SR/amlodipine results in superior SBP reduction with a safety profile in line with that of its components and tolerability equivalent to that of an angiotensin-converting enzyme inhibitor/amlodipine strategy.
Changes of health-associated quality of life (QоL) are an important criterion for evaluating the severity and treatment efficiency in patients with stable coronary artery disease. General and disease-specific questionnaires are used to assess QoL in contemporary clinical studies. The frequency of angina attacks is a key factor of QoL worsening in patients with stable coronary artery disease, independent from concomitant diseases and syndromes. Effort angina may lead to the decrease of physical activity level and ability to perform everyday activities, which in turn causes lifestyle changes and deterioration of QoL subjective perception. The use of the majority of contemporary antianginal drugs may be associated with «hemodynamic» side effects. Taking this into account, medications with metabolic mechanisms of antiischemic action, such as ranolazine, have a clear perspective. Ranolazine usage provides additional opportunities to improve QoL in patients with stable coronary artery disease, which may have a special value for treatment of the elderly patients.
The aim – to evaluate the dependence between inflammatory intensity and metabolic disorders and efficacy of systemic enzyme therapy (SET) in their correction in experimental condition.
Material and methods. We examined 40 rabbits which were kept on lipid-enriched diet for 8 weeks: 10 rabbits which took systemic enzyme therapy from 1st day of lipid-enriched diet (1st group), 10 rabbits which took systemic enzyme therapy from 5th day of experiment (2nd group) and 20 rabbits without treatment. At the beginning of the study and after 4th and 8th week blood of rabbits was examined on inflammatory intensity (with measurement of C-reactive protein (CRP), intracellular malondialdehyde (MDA), monocytes activity (MC)), oxidative stress intensity (MDA in serum), renin-angiotensin system activity with measurement of angiotensin converting enzyme activity (ACE act.). In addition, we studied lipid metabolism by measuring cholesterol and triglycerides blood levels, main classes of lipoproteins and their atherogenic potential (concentrations of cholesterol in circulating immune complex (CIC) and triglycerides in CIC), levels of glucose and HbAlc. Besides, tissue sensivity to insulin was evaluated in all rabbits.>br />Results. It was found that at the group without treatment CRP level was 18 times elevated, MDA MC level and MDA ser. level became 5.0 and 7.4 times higher respectively at the end of the 8th week in comparison with baseline (Р<0.001). ACE activity increased by 150 % (Р<0.001). Tissue sensitivity to insulin decreased nearly by 86 %, and as a result, glucose concentration in blood increased by 90 %, HbAlc level increased 3.7 times at the end of the study (Р<0.001). As a result of lipid peroxydation of triglycerides and cholesterol and elevation of their atherogenic potential, concentration in CIC were 5.6 and 4.5 times higher in comparison with control group (Р<0.001). At the 1st group we found 4 times lower levels of CRP (Р<0.001), 57 % lower concentration of MDA MC and in 3.7 times lower concentration of MDA ser. Levels of TG CIC and cholesterol in CIC decreased by 64 and 62 %, respectively, in comparison with group without treatment (Р<0.001).
Conclusion. Keeping rabbits on lipid-enriched diet resulted in development of disorders typical for metabolic syndrome. Using systemic enzyme therapy from 1st day of high-lipid diet lead to reduction of systemic inflammation intensity and immune reactivity, restoration of tissue sensitivity to insulin, normalization of blood lipid composition and reduction of its atherogenic characteristics. Therapeutic effects of SET increased during period of experiment.
The aim – to investigate the impact of VKORC1 polymorphism on dosage of warfarin and international normalized ratio (INR).
Material and methods. The study included 155 patients after heart valve replacement. Patients received warfarin treatment from initial dose of 5 mg daily. Subgroup A (n=35) included patients with INR values out of therapeutic range and subgroup B (n=120) – patients with INR values in the range 2.5–3.5. For determination of polymorphic variant G1639A of VKORC1 gene the method of PCR-RFLP has been used.
Results. The frequencies of 1639GG, 1639GA and 1639AA genotypes among the patients group were 37.42 %, 46.45 %, 16.13 %, respectively. The mean warfarin daily dose requirement was the lowest in patients with genotypes VKORC1 1639AA and 1639GA compared to patients with genotype 1639GG (Р<0.05). Patients with genotype VKORC1 1639АА had higher risk of over-anticoagulation (INR > 3.5) during warfarin therapy, compared to patients with wild-type genotype (Р<0.05).
Conclusions. Genotypes 1639GA and 1639AA are frequent enough to provide background for personalized warfarin dosing.
Kharkiv Medical Academy of Postgraduate Education, Ukraine
The problems associated with arterial hypertension, being a powerful, independent and potentially easily detectable and correctable risk factor of fatal cardiovascular events, are reviewed. Despite the development and introduction into clinical practice of highly effective anti-hypertensive medications, adequate control of blood pressure is achieved in
only 30–50 % of patients. The reasons for this low rate of blood pressure effective control are the difficulty of the target blood pressure achieving with monotherapy and low patients adherence to treatment with several drugs. This review discusses the advantages of antihypertensive medications fixed combinations in general, and the combination of angiotensin-converting enzyme inhibitor enalapril and the dihydropyridine calcium antagonist nitrendipine, in particular. The results of clinical studies showing high efficacy of this fixed combination in achieving target blood pressure, good tolerability, organ-protective properties and positive influence on the prognosis are presented.
The effect of a new non-opioid analgetic drug pirodazol upon hemodynamic parameters was studied as aspect of safety pharmacology. The study was conducted on white rats. Pirodazol was administered intramuscularly in doses of 1/20 LD50, 1/4 LD50, 1/2 LD50 (1,1; 5,5 and 11 mg kg respectively). Dose-related specific hemodynamic changes were elicited starting from the 30th min after single pyrodazol injection administration. Maximal hypotensive effect (up to -51.66 %) was achieved at the dose of 11 mg/kg. The hypotensive effect was accompanied by compensatory tachycardia, decreased cardiac output (up to –62.8 %) and systemic vascular resistance (up to –30.6 %). At a dose of 1.1 mg/kg hemodynamic changes were not significant, apart from changes of total peripheral vascular resistance at 30 and 60 min after administration.
Zofenopril It is a sulfhydryl-containing, lipophilic ACE inhibitor with a very high affinity for cardiac ACE. It shows some physical and chemical properties, features of pharmacodynamics and pharmakokinetics which are absent in other drugs of this class. Most clinical value have high lipophilicity, which is associated with the prolonged effect of tissue ACE inhibition, antioxidant activity and cardioprotective properties. Sufficient experience of zofenopril application is presently accumulated in different cardiovascular diseases. Zofenopril is an effective antihypertensive ACE inhibitor that has been shown to improve blood pressure control in international placebo controlled randomised clinical trials and was effective as antihypertensives of other basic classes. In preclinical studies the sulfhydryl-group–containing ACE inhibitor zofenopril significantly reduced the frequency and severity of exertional and spontaneous cardiac ischemia. The anti-ischemic and cardioprotective effects of zofenopril have been confermed by the results of randomized controlled studies carried out under the SMILE program in patients with myocardial infarction. In the SMILE study, the early administration of zofenopril in nonthrombolyzed patients with myocardial infarction has been shown to reduce the incidence of death or severe congestive heart failure. The results of the SMILE-ISCHEMIA study extend the use of zofenopril in terms of cardioprotection and prevention of coronary events from the early to the late phase of myocardial infarction. In light of these results, zofenopril may be recommended as a secondary prevention drug treatment in post–myocardial infarction patients with coronary artery disease.