Rational Pharmacotherapy in Cardiology

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Vol 9, No 5 (2013)
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472-481 929

Aim. To determine the most significant factors forming patient’s attitude to treatment and factors of adherence to treatment preceding hospitalization in patients with acute coronary syndrome (ACS).
Material and methods. A register of patients admitted to Lyubertsy Regional Hospital №2 for ACS from 01.12.2011 to 01.12.2012 was used in the study. A total of 272 patients (men – 157, women – 115) were enrolled into the study. Age range was between 31 and 89 years, mean age was 63.6±12.6 years. Acute myocardial infarction was diagnosed in 181 patients, unstable angina pectoris – in 91 patients. While in hospital all the patients had filled out the questionnaire on therapy adherence.
Results. Half of the 272 patients (133 persons) enrolled into the study had regularly been followed-up for chronic diseases in different medical centers; 138 patients (50.7%) had not been followed-up before the reference hospitalization. According to the valid Morisky-Green test results 120 patients (44.1%) were adherent to treatment, in 141 (51.8%) patients the adherence was unsatisfactory, 11 persons (4.1%) did not answer the test questions. Younger patients adhered to doctors’ recommendations better. According to the patients (125 patients – 46%) the most effective strategy to improve treatment adherence was the obtaining of detailed information about their disease and methods of its treatment provided by the doctor. 32 patients (11.8%) pointed out the importance of lowering drug costs. 11 patients of 272 respondents demanded more care from their doctor; 4 persons suggested that better quality of medical care organization would help to ameliorate treatment adherence. Regular follow-up for chronic diseases with detailed informing about the condition by a physician positively influences adherence to recommended therapy. Patients of commercial medical centers and patients without any medical follow-up least of all adhered to treatment.
Conclusion. Specially designed questionnaire allowed to determine the most significant factors that form patients’ attitude to therapy preceding the reference hospitalization and factors of adherence to treatment prescribed before the hospitalization. All the significant factors were related to the physician-patient relationships, what emphasizes the important role of both doctors and patients in improvement of treatment adherence.

482-487 551

Aim. To study the endothelium status and determine the correlation between endothelial dysfunction and glucose metabolism in men with gout associated with arterial hypertension (HT).
Material and methods. Patients (n=175, all are males) with gout were enrolled into the study. Ambulatory blood pressure monitoring (ABPM) was performed in all patients. Endothelial function was studied in tests with reactive hyperemia (endothelium-dependent reaction) and nitroglycerin (endothelium independent reaction) in brachial artery by ultrasonic Doppler examination. The level of nitrite-nitrate and endothelin-1 in blood serum was determined by ELISA technique. Fasting blood glucose and oral glucose tolerance tests were performed as well as fasting insulin blood level was determined by immunoenzyme method. Insulin-resistance index (HOMA-IR) was calculated. Patients with HOMA- IR>2.77 were considered as insulin-resistant.
Results. Patients with gout demonstrated endothelial deterioration associated with activation of nitroxid producing function, elevation in endothelin-1 serum level (1.36 fmol/ml [0.91; 2.32 fmol/ml] vs 0.19 fmol/ml [0.16; 0.27 fmol/ml] in controls, p<0.05) and impairments of endothelium-dependent vasodilation (6.4% [3.3; 7.3%] vs 17.8% [12.7; 23.9%] in controls, p<0.05). The revealed changes were the most marked in patients with gout associated with HT. The correlation between some endothelial dysfunction in- dices and glucose metabolism was observed.
Conclusion. ABPM, brachial artery endothelium-dependent vasodilation and glucose metabolism status should be studied in patients with gout. Complex treatment of cardiovascular diseases in patients with gout should include ω-3 polyunsaturated fatty acids, angiotensin receptor antagonists should be used for antihypertensive therapy.

488-493 485

Aim. To study the clinical and functional parameters of patients after acute Q-wave myocardial infarction (Q-MI) depending on the concomitant metabolic syndrome (MS). Material and methods. Men after Q-MI (n=79; aged 51.7±8.9 years) were included into the study. Patients were divided into two groups depending on the MS presence or absence. Doppler echocardiography and determination of the serum C-reactive protein (CRP) level were performed in all patients on the 10-14 days after Q-MI, and treadmill test was performed in 25 patients.
Results. Left ventricular ejection fraction was 12% lower and the CRP level was 2 times higher in MS patients versus these in non-MS patients (p<0.01). The silent segment ST depression ≥1.0 mm were more often observed in MS patients compared with this in non-MS patients (40% vs 5%; respectively, p<0.05).
Conclusion. The MS presence complicates the post-infarction period by early heart failure progression, characterized by elevated CRP levels and more frequent occurrence of silent myocardial ischemia.

494-499 569

Aim. To assess the quality of drug therapy and its correspondence with current clinical guidelines in patients with proven stable ischemic heart disease (IHD) before admission, during inpatient stay in hospital and after hospital discharge.
Material and methods. Data on 550 patients (from PROGNOZ IBS register) with detected stenosis of at least one coronary artery ≥50% were included in the analysis. Assessment of the quality of drug therapy was conducted in patients who made a follow-up visit in 3.9 years after the reference hospitalization (n=303) using a specially designed questionnaire. Adherence to treatment was studied using a phone survey.
Results. According to PROGNOZ IBS register data we revealed low prescription frequency of drugs with proven effects on the cardiovascular risk in patients with stable IHD prior to hospital admission and significant pharmacotherapy improvement in specialized cardiology hospital. In specialized hospital the rate of aspirin use increased by 30%, statins - by 80%, beta-blockers - by 70%, ACE inhibitors - by 60% (p<0.0001). These medications prescription frequency decreased by 15-20% on the average in 3.9 years after discharge.
Conclusion. We found significant improvement in pharmacotherapy quality of patients with stable IHD during stay in cardiology hospital, and pharmacotherapy quality reduction after discharge.

500-504 553

Aim. To evaluate primary care efficacy in patients with chronic heart failure (CHF).
Material and methods. Outpatients (n=139) with CHF and 35 primary care physicians were included into the study. The evaluation of drug therapy and patient awareness of the principles of non-drug CHF treatment were performed. An anonymous survey among doctors in terms of current CHF guidelines knowledge, patient information provided by physicians, and doctors’ burnout status was also carried out.
Results. Only 39% and 10% of CHF outpatients received target doses of ACE inhibitors/sartans and beta-blockers, respectively. Majority of CHF outpatients and their doctors need in additional education/training. 56% of primary care physicians demonstrated an emotional burnout.
Conclusion. Author considers it essential to distribute short pocket-guidelines on CHF management among primary care physicians, and to reduce the load on primary care physicians with simultaneous strengthening of their performance control.

505-510 1087

Aim. To evaluate the therapeutic equivalence between generic perindopril (Parnavel, LLC Ozone, Russia) and the original perindopril (Prestarium A, Laboratories Servier, France). Material and methods. Patients with arterial hypertension, grade 1-2 (n=40, aged 35-75 years) were included into the open randomized cross-over trial. The previous anti- hypertensive therapy was discontinued before study for 14 days in all patients. Each of the patients was randomized for alternate 8-week treatment with the original (Prestarium A) and generic (Parnavel) perindopril. Treatment efficacy was assessed by the achievement of target blood pressure (BP) <140/90 mm Hg. The drug dose was increased in the efficacy lack and inapamide was added if necessary. Therapy was discontinued for 14 days after 8 weeks of treatment with the first randomization drug, and the same therapy course with the other study drug was carried out. Side effects were also recorded.
Results. A significant reduction in systolic (SBP) and diastolic BP (DBP) was found in patients of Parnavel group by 28 mm Hg (19%) and 17 mm Hg (19%), respectively. In the patients of Prestarium A group SBP and DBP reduction was 27 mm Hg (18.5%) and 16 mm Hg (18.7%), respectively. After 2 months of therapy the target BP level (<140/90 mm Hg) was achieved in 95% and 90% of patients in Parnavel and Prestarium A groups, respectively. Drug tolerability was comparable.
Conclusion. Efficacy and tolerability data demonstrated therapeutic equivalence of generic perindopril (Parnavel) to the original perindopril.

511-518 929

Aim. To study the clinical equivalence of the two low-dose combined drugs on the base of generic and original bisoprolol and hydrochlorothiazide (HCTZ): BISANGIL® (Ozon, Russia) and LODOZ® (NYCOMED, Merck KGaA, Germany) in patients with arterial hypertension (HT) of 1-2 degrees.
Material and methods. Patients with HT of 1-2 degrees (n=30; 11 men and 19 women; aged 62.7±10.7 years) were included in open crossover randomized trial. Duration of the study for each patient was 18 weeks: two 6-week courses of active treatment with each drug and two 2-week washout periods prior to each treatment course. The sequence of treatment courses was determined by randomization. Increase in bisoprolol dose and/or amlodipine addition occurred when effect was not sufficient. Therapy effectiveness (office blood pressure (BP), heart rate) and safety was monitored at visits.
Results. BP reduction after 6 weeks of therapy was -21.6±11.1/10.4±11.3 mm Hg in LODOZ® group and -22.9±9.7/11.7±13.5 mm Hg in BISANGIL® group (p<0.0001 for both), intergroup differences were insignificant. Target BP after 6 weeks of therapy was achieved in 26 (87%) and 28 (93%) patients, respectively.
Conclusion. The therapeutic equivalence of the studied fixed combinations of bisoprolol/HCTZ was demonstrated in treatment of patients with HT of 1-2 degrees.


519-524 539
The causes of cognitive impairments (CI) in patients with arterial hypertension and supraventricular arrhythmias and CI prevalence rate in these patients are presented in details.


525-531 850
The clinical significance of the patient genetic characteristics in the individual pharmacological response to oral anticoagulants is considered. Possible tactics of warfarin dosing and new oral anticoagulants choice on the basis of pharmacogenetic testing as well as indications for this approach in clinical practice are discussed. It should increase efficacy and safety of anticoagulant therapy.
532-541 511

Antisense oligonucleotides (ASO) technology in elaboration of drugs for lipid metabolism correction is discussed. The main ASO types and modes of its action on the target mRNA are analyzed. Advantages and disadvantages of different ASO are considered in the context of requirements for their therapeutic applications.
Methods of ASO chemical modification; advantages and disadvantages of different ways of ASO delivery into the cells; developments state of ASO-drugs for therapy of lipid metabolism disturbances; data from clinical trials of these drugs are described.


542-550 565
The problem of inflammatory cardiomyopathy is discussed. The etiology, pathogenesis, diagnosis and treatment of inflammatory cardiomyopathy are considered with focus on the role of parvovirus B19.
551-556 474
Disadvantages of vitamin K antagonist warfarin and the benefits of new anticoagulants, including dabigatran etexilate, in the stroke prevention in patients with atrial fibrillation are considered. Factors that influence the choice of dabigatran dose in different individuals are discussed. Dabigatran treatment in special conditions is considered: during stroke development; in electrical or pharmacological cardioversion; in invasive or surgical procedures; during bleeding. Possible organizational system of thromboembolic events prevention in patients with atrial fibrillation is presented.
557-563 1098
The article deals with the problem of arterial hypertension in systemic vasculitis. Data on the epidemiology, pathogenesis, and clinical aspects of hypertension in systemic vasculitis are presented.
564-569 554
Review of large of trials that prove the positive impact of high-dose lipid-lowering therapy on the prognosis in patients with ischemic heart disease (IHD) are presented. The data on the efficacy of the lipid profile correction by lipid apheresis in patients with hypercholesterolemia that is refractory to optimal medical therapy are showed. The results of the large trials (LIPS, ARMYDA, NAPLES II, ARMYDA-RECAPTURE, Post-CABG, TNT) and meta-analyzes on the role of statins, prescribed before and after coronary artery bypass surgery and stenting, in reducing the risk of early and late cardiac events and the need for repeat myocardial revascularization are analyzed. The issue of therapeutic apheresis should be considered in cases of refractory hypercholesterolemia according to ESC/EAS Guidelines for the management of dyslipidaemias (2011). The tendency to reduction in the risk of stent restenosis and vein graft lesions after lipid apheresis is found in very high risk patients with IHD and refractory hypercholesterolemia that underwent coronary stenting or bypass surgery.
570-576 529
One of the pressing problems of modern cardiology is the cardiac complications risk evaluation and correction in noncardiac surgery. Recent international guidelines on this issue have focused on the pharmacological prevention of complications while reducing the preoperative examination and preventive revascularization. The reason for this experts position has been a series of studies DECREASE, performed in the Erasmus Medical Center (The Netherlands) under the supervision of Professor D. Poldermans. However, this summer the results of these studies have found no scientific value because of the significant irregularities in their conduct. It makes to have a new look at the problem of perioperative medicine, to rethink the available scientific evidence. In this review we discussed in detail the use of beta-blockers in noncardiac surgery in view of new circumstances.


577-581 499
Questions of metabolite therapy with drugs based on glutamic acid in patients with chronic heart failure are considered. Possible modes of action of these drugs are presented. Results of the proper study of glutamic acid based drug in chronic heart failure are presented as examples.


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