Rational Pharmacotherapy in Cardiology

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Vol 8, No 2 (2012)
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141-148 444

Aim. To evaluate main factors influencing admission time to cardiovascular care unit in patients with acute coronary syndrome (ACS). Material and methods. Anonymous questionnaire was used to study factors associated with prehospital delay. A total of 363 patients aged 63.2±12.3 (24-89 years) were enrolled into the study: women – 132 (37%), men – 231 (63%). Results. The main reason for emergency call was typical pain syndrome (87%). 52% of the patients experienced the pain syndrome for the first time, the others noted change in the pain characteristics. 28% of the patients did nothing to relieve the chest pain; only one third of the patients used short-acting nitrates. The main reasons for delay in emergency call were the follows: hope that the symptoms will pass off aidless, unwillingness to disturb medical staff, various family circumstances and so on. Almost third part of the patients sought medical attention more than one hour after pain syndrome onset, about half of the patients called an ambulance within the first 40 minutes. Women sought medical advice later than men and used nitroglycerin less often. Experience of myocardial infarctions decreased in time before emergency call and increase in frequency of nitroglycerin intake before ambulance arrival but these correlations were weak (r≤0.25). Conclusion. Very high and high cardiovascular risk patients underestimate severity of possible complications of their disease and necessity for emergency call, they are also not familiar with the first aid algorithm in emergency cases. To reduce prehospital delay hospital and out-patient clinic doctors have to regularly inform high-risk patients and their relatives about the ACS symptoms and methods of the first aid.

149-153 701

Aim. To study the pharmacokinetic, pharmacodynamic and pharmacoeconomic parameters of the original and generic enalaprils in the treatment of the elderly patients with hypertension (HT). Material and Methods. Patients (n=40) 75–90 years with HT were included in the open randomized comparative study. Patients were randomized into two groups. Patients of the group 1 received generic enalapril, patients of the group 2 — the original enalapril consisting of combined therapy. Pharmacokinetic single-dose study of original and generic enalapril were carried out with high-performance liquid chromatography. Pharmacodynamic study was carried out in single-dose administration as well as after 2 and 4 weeks of treatment with original and generic enalapril. Pharmacoeconomic evaluation of antihypertensive drugs was carried out on the basis of cost minimization analysis. Results. Original enalapril dose necessary to achieve the target blood pressure (BP) was 10 mg/day as a part of two-component therapy. This for generic enalapril was 20 mg/day consisting of three- or four-component therapy. Both drugs have shown an acceptable safety profile. Pharmacokinetic differences were revealed between original and generic enalapril: area under pharmacokinetic curve 204.14 (202.25–206.05) vs 136.23 (134.17–137.65) ng*h/ml, respectively; time of the drug retention in the blood plasma 5.42 (5.26–5.76) vs 4.88 (4.86–4.94) hours, respectively; p<0.001. Original enalapril demonstrated more stable 24-hour antihypertensive effect in once daily administration in comparison with this in generic enalapril: trough/peak ratio 78.67% (47.61–91.35%) vs 44.96% (32.44–55.49%), respectively , p<0.01. The average daily cost of combined therapy containing generic enalapril was 15.91 rubles per patient, while this in combined therapy containing original enalapril — 13.78 rubles per patient. Conclusion. Medicines on the basis of original and generic enalapril have pharmacokinetic, pharmacodynamic and pharmacoeconomic differences.

154-157 474

Aim. To study changes in quality of life (QoL) in patients with atrial fibrillation (AF) treated with warfarin after leaving the international clinical trial. Material and Methods. Patients with AF who were managed at cardiology department of the University Hospital participated in the study. Patients of the main group (n=79) completed the international clinical trial with warfarin titration to therapeutic doses and subsequent therapy monitoring at least 1 year . Patients of the control group (n=23) had never taken part in clinical trials. QoL was evaluated with the 36-Item Short-Form Health Survey (SF 36) questionnaire after international clinical trial living or hospital discharge (initially) and in 3, 6 months of follow-up in outpatient clinic. Results. The most significant changes were observed in the first 3 months. In patients of the main group after clinical trial leaving physical component of QoL decreased from 65 (52.0-77.0) to 52 (25.0–55.0) points (p<0.05) and emotional component – from 65 (55.0-70.0) to 60 (50.0–65.0) points (p<0.05). At the same period opposite dynamics was observed in patients of the control group after hospital discharge. Physical component of QoL increased from 55 (25.0-65.0) to 65 (52.0–77.0) points (p<0.05) and emotional component - from 60 (47.5- 65.0) to 70 (60.0–75.0) points (p<0.05). In the next 3 months QoL levels have not changed significantly in patients of the both groups. Conclusion. International clinical trial living affects QoL in patients with AF . The physical component of QoL worsens most significantly.

158-162 489

Aim. To study the prognostic value of syncope in non-massive pulmonary embolism (PE). Material and methods. Patients (n=64; 35 men and 29 women; aged 52±13 years) with non-massive PE were examined. 13 (20%) patients had a high risk of death according to the ESC criteria, and 51 (80%) — an intermediate risk. PE diagnosis was verified by X-ray contrast angiography or computer angiography of the pulmonary artery. Patients were split into 2 groups: patients of group 1 (n=14) had syncope episodes during the last 24 hours (from 1 to 30), and group 2 (n=50) — did not have. Groups did not differ by age, sex and disease duration. Comparative analysis of clinical and instrumental data, hospital mortality was made. Results. The significant differences for most parameters in the studied groups were not found. Combination of syncope and right bundle branch block on ECG was observed more often in PE patients of high risk mortality: 50% vs 14.2% in groups 1 and 2, respectively (p=0.004). High risk of death was defined 3 times more often in group 1 than this in group 2: 42.8% vs 14% (p=0.017). Syncope at the onset of non-massive PE clinical manifestations associated with more often hypotension development — 42.8% vs 14% in groups 1 and 2, respectively (p=0.017). Patients of group 1 needed in thrombolytic therapy 3 times more often than patients of group 2: 50% vs 16%, respectively. Hospital mortality did not differ significantly — 0 and 2% in groups 1 and 2, respectively. Conclusion. Syncope in non-massive PE, especially in combination with right bundle branch block on ECG, may be considered as a possible criterion for high risk of complications and can be rationale for thrombolytic therapy in addition to standard therapy. Designed studies on prognostic significance of syncope in PE, depending on mass of pulmonary artery lesions and risk stratification are necessary.

163-167 370

Aim. To assess the real rate of dual antiplatelet therapy (DAT, acetylsalicylic acid + clopidogrel) use in patients having appropriate indications according to current clinical guidelines and to study the possibility of prescription rate improvement by education activity directed to doctors. Material and methods. The study consisted of 3 parts. Parts I and II present the results of two questionnaire surveys of patients with acute myocardial infarction, or stenting, who needed in DAT according to current clinical guidelines. The real use of the DAT was assessed in part III on the basis of the multicenter study conducted in different regions of Russia (ROMB study) in a large sample of patients having DAT indications. Results. Part I - PROGNOZ-IBS study. According to the questionnaire survey only 112 out of 239 patients (47%) having an absolute indications, received DOT. Part II - phone survey of patients with acute myocardial infarction in two towns of Lyubertsy and Podolsk. 28 of 71 patients (39%) took the DAT (from some days to 6 months) and 35 patients (49%) — did not take it. Part III - ROMB study. 519 patients did not take DAT, at that 259 (50%) in hospital and 260 (50%) - in out-patient clinic. 521 patients took DAT according to indications, at that 238 (46%) in hospital and 283 (54%) - in out-patient clinic. Conclusion. Less than 50% of patients, having direct indications, received DAT in the real clinical practice. The prescription rate can be improved due to education activity directed to doctors and increase in clopidogrel drugs affordability.

168-172 451

Aim. To compare effects of acetylsalicylic acid (ASA) and two clopidogrel drugs on residual platelet aggregative reactivity (RPAR). Material and methods. Patients (n=40) with ischemic heart disease aged under 70 years were involved into the crossover study. Clinical examination included questionnaire survey , blood pressure (BP) measurement, ECG registration, 24-hour ECG and BP monitoring, determination of blood levels of total cholesterol, high density lipoproteins, triglycerides, transaminases, and creatinine, complete blood cell count, including platelets number and hemoglobin level. Besides evaluation of the platelet aggregation by optical aggregometry was performed initially , after one week ASA treatment and after every next 3 week clopidogrel treatment period.  Results. RPAR during ASA monotherapy was 56.4±0.3%. There were no significant differences in effects of original and generic clopidogrel on RPAR. Сlopidogrel therapy reduced RPAR more significantly (42.2±0.2%) than ASA monotherapy did (p=0.0003). Authors proposed definition for high level of RPAR during therapy - it is platelet aggregation more than 46%. Data analysis taking into account this criterion showed that a number of patients with high RPAR was 70 and 30% among patients treated with enterosoluble ASA and clopidogrel, respectively. Conclusion. Study results show that a significant number of patients receiving antiplatelet monotherapy does not achieve the target level of RPAR(<46%). These results may be a rationale for combined therapy in patients of this type.

173-178 440

Aim. To carry out a comparative pharmacoeconomic analysis of two different types of antihypertensive therapy in patients with arterial hypertension (HT). Material and methods. 38 patients with essential HT (aged 18 to 70 years, 11 males and 27 females) associated with metabolic syndrome, and having a history of previous ineffective antihypertensive therapy were included into the study. The patients were randomized into 2 groups. Patients of V/A group received a fixed combination of valsartan and amlodipine (Exforge, Novartis) in dose of 5/160 and 10/160 mg depending on blood pressure (BP) level. Patients of L/A group received losartan (Lorista, KRKA) in dose of 100 mg and amlodipine (Tenox, KRKA) in dose of 5 and 10 mg. Treatment duration was 24 weeks. If target level of BP was not achieved during 12 weeks, indapamide retard was added to the therapies (Ravel SR, KRKA). Dinamics of BP and left ventricular mass index (LVMI) were considered. Cost-effectiveness method of analysis was used. Results. In V/A group 75% of patients achieved target BP levels for 24 weeks, while in L/A group — 33.3% of patients, and 16.7% of patients more after indapamide addition. L/A therapy cost was lower in comparison with this of V/A therapy: 57864.24 vs 156671.0 rubles per 24 weeks, respectively. Calculation shows that additional cost of 669.23 rubles during 24 weeks is needed to achieve BP target level in every next patient when V/A therapy is used instead of L/A therapy. LVMI reduction by 1% took 1015.13 rubles cost in V/A group and almost 6 times more in L/A group. Conclusion. Pharmacoeconomic analysis revealed that generic combination of L/A is the most cost-effective for BP reduction. Very low cost is required to achieve additional effect with original fixed V/A combination. V/A combination is the most economical for the left ventricular hypertrophy reduction. Thus, V/A combination is rational for use in HT patients with severe target-organs damage.

179-184 403

Aim. To compare two therapies based on the use of original or generic drugs in patients with stable ischemic heart disease (IHD). Material and methods. Patients (n=120), aged 40–72 (58.7±7.7) years, 93 men and 27 women, with stable angina, functional class (FC) II (n=117, 97.5%) and III (n=3, 2.5%), were included in the multi-center open randomized study with parallel groups. Patients were randomized into 2 groups: group 1 (n=59) received therapy with original drugs only , and group 2 (n=61) — with generics ones only. Efficacy of the therapies was evaluated by the rate of achievement of target blood pressure (BP<130/80 mm Hg), heart rate (HR=55–60 beat per minute) and cholesterol of low density lipoprotein (LDL<70 mg% or 1.8 mmol/l), as well as by the degree of reduction in the angina attacks rate, the need in short-acting nitrates, and the angina FC. Treatment duration was 12 weeks. Results. After randomization both groups of patients were comparable by the main clinical indicators. The rates of target levels achievement were the following in group 1 vs group 2, respectively: for BP - 54 vs 44%, p=0.08; for HR - 51 vs 53%, р=0.66; LDL cholesterol - 27.7 vs 9.9% of patients, p=0.002. There were no significant differences between original and generic drugs effects on the angina pectoris symptoms dynamics, as well as their influence on glucose, bilirubin, creatinine, alanine and asparagine transaminases, and creatine phosphokinase blood levels dynamics. The original and generic drugs prescription rates, a total number of prescribed drugs and prescribed doses were comparable in both groups at the end of the study. Three patients dropped out of the trial, the frequency of adverse events was 3.4% in group 1 and 11.5% — in group 2 (p=0.09). Conclusion. Generic drugs with proven bioequivalence, used in the KARDIOKANON study , demonstrated their clinical equivalence to original drugs. The use of these drugs in patients with stable IHD may provide efficacy and quality of therapy comparable with these in original drugs.

185-189 415

Background. Shiftwork is considered as one of risk factors of arterial hypertension (HT) and metabolic disorders. Aim. To study effects of different types of shift plan on HT and the metabolic disorders development. Material and Methods. 1091 men were included in the study. Patients were split into subgroups according to age (20–29, 30–39, 40–49, 50–59 years old) and shift plan (steady or shiftable work schedule). HT (blood pressure >130/85 mm Hg), abdominal obesity (waist circumference >94 cm), disorders of glucose metabolism were revealed. Results. HT prevalence in patients with shiftwork was significantly higher than that in employees with steady work schedule (34.4 vs 27.4%, respectively; р<0.01). In patients with shift and steady work schedule significant differences in abdominal obesity (69.2 vs. 19.3%, respectively; p<0.001) and glucose metabolism disorders rates (19.0 vs. 10.6%, respectively; p<0.001) were also found. Differences between groups in prevalence of hypercholesterolemia and metabolic disorders cluster were not significant. HT associated with metabolic disorders dominated among steady work patients aged 40-49 years (56.7%) in comparison with shiftable work patients (20.0%), p<0.01. Conclusion. Shiftwork may be considered as a risk factor of HT and metabolic disorders in males.

190-195 440

Aim. To study blood levels of non-esterified fatty acids (NEFAs) and adenyl nucleotides, and fatty acids levels in lipids of erythrocyte membranes in patients with primary gout associated with arterial hypertension (HT). Material and methods. 175 male patients with primary gout were included in the study. According to 24-hour blood pressure (BP) monitoring results patients were split into two groups: 74 patients with normal BP (group 1) and 101 patients with HT (group 2). 29 healthy age-comparable subjects were included into control group. Uric acid, total NEFAs and glycerol blood levels were studied in all patients. Adenyl nucleotides (ATP , ADP and AMP) levels were determined in erythrocytes. Higher fatty acid levels were specified in lipids of erythrocyte membranes, including the following acids: myristinic (С14:0), palmitinic (С16:0), stearic (С18:0), pentadecanic (С15:0), heptadecanic (С17:0), pentadecenic (С15:1), heptadecenic (С17:1), palmitooleic (С16:1), oleic (С18:1), linoleic (С18:2ω6), α-linolenic (С18:3ω3), γ-linolenic (С18:3ω6), dihomo-γ-linolenic (С20:3ω6), arachidonic (С20:4ω6), eicosapentaenoic (С20:5ω3), and docosapentaenoic (С22:5ω3). Results and discussion. Hypertensive patients with gout demonstrated higher NEFAs blood level and greater changes in ATP-ADP-AMP system than normotensive gout patients and healthy subjects as well as 2.2 and 3.7 times higher NEFAs/ATP ratio, respectively. In hypertensive patients with primary gout the composition of fatty acids in erythrocyte membranes lipids changed due to increase in saturated fatty acids amount and decrease in unsaturated fatty acids amount, at that monoenic acid levels increased while polyenic acid levels decreased in unsaturated acids composition. Hypertensive patients with gout shown 1.3 and 2.5 times less levels of ω-3 poly-unsaturated fatty acids (PUFA) than normotensive gout patients and healthy subjects, respectively. At the same time ω-6 PUFA levels changed in bidirectional manner: γ-linolenic and dihomo-γ-linolenic acids levels rose, while arachidonic acid amount was 1.2 and 2.3 times less in comparison with these in gout patients with normal BP and healthy subjects.  Conclusion. Study data demonstrate that fatty acid metabolic disturbances possibly contribute to HT development in patients with primary gout.


196-200 1173

The clinical case of a rare proarrhythmic effect of antiarrhythmic drugs with a poor prognosis (medication-induced atrial flutter in a patient with "malignant" Kent’s bundle) is presented. Radiofrequency ablation (RFA) is the most justified treatment method in patients with WPW-syndrome and "malignant" Kent’s bundle. RFA in descripted case has been postponed due to technical reasons. While waiting for RFA and after consideration of the potential risks and benefits the decision to use antiarrhythmic drugs to block the additional bundle was made. Paroxysm of broad-complex tachycardia developed on the third day of the treatment. It was regarded as a paroxysm of atrial fibrillation/flutter in the patient with WPW syndrome induced by taking antiarrhythmic drugs class 1C (allapinine). Review of the literature on the atrial fibrillation induced by antiarrhythmic of 1C class, and association of atrial fibrillation with WPW-syndrome is presented.

201-204 834

Data on angiotensin II receptor blockers, one of the main drug classes used in cardiology , are presented. The advantages of this drugs class are highlighted with the focus on telmisartan. Additionally clinical example of successful telmisartan application in patients with hypertension, high risk of cardiovascular complications, and obesity is presented.


205-210 469

Acetylsalicylic acid (ASA) use in the primary and secondary prevention of cardiovascular diseases is focused. Mode of ASA disaggregation action is discussed. Data of randomized controlled trials on ASA efficacy and safety in primary and secondary prevention are presented. The main groups of patients who are required the ASA prevention according to current clinical guidelines are indicated. ASA benefit-risk ratio, as well as ways to improve the safety of antiplatelet therapy are presented, including use of enteric-soluble ASA forms.

211-219 777

A comparison of ivabradine and omega-3 polyunsaturated fatty acids, drugs with principally different mechanisms of action, is presented in patients with chronic heart failure (CHF) on the base of GISSI-HF and SHIFT trails results. It is essential to compaire an effect of these drugs on the morbidity and mortality in combined therapy of patients with CHF , because each additional drug may change in compliance to treatment, induces additional costs or may be a reason of new side effects. Additional (to standard therapy) effects of ivabradine and omega-3 polyunsaturated fatty acids are discussed.

220-225 552

At the present there are principles of cardiopulmonary resuscitation (CPR) which are reflected in the recommendations of the AHA and ESC of 2010. They include strict rules on well-timed and proper closed-chest cardiac massage. According to these rules chest compressions should be repeated at least 100 times per minute at a depth of not less than 5 cm. To comply with the standards is not easy even for skilled staff, operator tiredness quickly leads to decrease in CPR quality. Various mechanical devices for closed-chest cardiac massage are used nowadays. One of them is LUCAS system. In some studies LUCAS system showed an efficacy and safety comparable with manual closed-chest cardiac massage. Design features of the LUCAS device do not disturb other life maintaining activities — defibrillation, mechanical ventilation. The device permeability for X-rays makes possible the use of LUCAS in cath labs, if CPR is needed during the intervention procedure. LUCAS system can serve as an alternative tool for CPR. It can be used in intensive care units, as well as be at the disposal of special emergency teams.


226-232 479

Arterial hypertension (HT) takes leading position in the structure of morbidity and mortality among the cardiovascular diseases in the economically developed and developing countries of the world. Despite progress in treatment of this disease, a number of people with uncontrolled or resistant HT increases. There is a problem of inefficiency of therapy or lack of patients' adherence to treatment. Therefore, search for new approaches to treatment of HT continues. Current most effective agents for blood pressure control, and possible future antihypertensive agents, are related to groups of agents, which inhibit renin–angiotensin–aldosterone system (RAAS). Novel targets for antihypertensive therapy could include the angiotensin II type 2 and type 1 receptor , neutral endopeptidase, aldosterone synthase, renalase, endothelin receptors, (pro)renin receptors, vaccine against RAAS components. Development of novel agents and approaches to HT therapy is discussed.

233-236 704

The role of selective I1 imidazoline receptor agonists and moxonidine in particular , in modern antihypertensive therapy is discussed. Moxonidine advantages, namely positive effects on insulin resistance, endothelial dysfunction, lipid profile, and plasma fibrinolytic activity are considered.

237-241 564

The results of large-scale clinical trials have convincingly demonstrated the effectiveness of acetylsalicylic acid (ASA) in primary and secondary prevention of atherothrombotic events. Studies on the safety of different ASA formulations have been continuing. Magnesium hydroxide included in combined medicine, Сardiomagnil, prevents ASA adverse effects on the gastric mucosa and reduces in severity of dyspeptic symptoms.

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