Rational Pharmacotherapy in Cardiology

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ISSN / EISSN : 1819-6446 / 2225-3653
Current Publisher: Stolichnaya Izdatelskaya Kompaniyaizdat (10.20996)
Total articles ≅ 1,545
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, A. A. Shavarov, M. V. Vatsik-Gorodetskaya
Rational Pharmacotherapy in Cardiology, Volume 17, pp 62-72; doi:10.20996/1819-6446-2021-02-03

Abstract:
Atrial fibrillation and renal dysfunction often coexist, each disorder may predispose to the other and contribute to worsening prognosis. Both atrial fibrillation and chronic kidney disease are associated with increased risk of stroke and thromboembolic complications. Oral anticoagulation for stroke prevention is therefore recommended in patients with atrial fibrillation and decreased renal function. Each direct oral anticoagulant has unique pharmacologic properties of which clinician should be aware to optimally manage patients. The doses of direct oral anticoagulants require adjustment for renal function. There is debate regarding which equation, the Chronic Kidney Disease Epidemiology (CKD-EPI) equation vs. the Cockcroft-Gault equation, should be used to estimate glomerular filtration rate in patients with atrial fibrillation treated with direct oral anticoagulants. Our review tries to find arguments for benefit of direct oral anticoagulants in patients with renal dysfunction.
, V. V. Butsev, R. R. Suleymanov
Rational Pharmacotherapy in Cardiology, Volume 17, pp 73-82; doi:10.20996/1819-6446-2021-02-09

Abstract:
The present work is devoted to the analysis of modern publications on various aspects of the development and course of ischemic stroke in the presence of acute myocardial infarction. A literature search was conducted on the websites of cardiological and neurological societies, as well as on the PubMed, EMBASE, eLibrary databases using the keywords: myocardial infarction, acute coronary syndrome, stroke, acute cerebrovascular accident, myocardial infarction, acute coronary syndrome, stroke. The authors of this review found that although stroke is a relatively rare complication of myocardial infarction, its prevention is an extremely significant task, since it is associated with high mortality, disability and a significant increase in the cost of treatment. So, it is extremely important to detect thrombosis of the left ventricular cavity in a timely manner, to register preexisting atrial fibrillation that occurs earlier or for the first time, followed by the appointment of anticoagulant therapy. Timely reperfusion treatment, the use of statins and modern dual antithrombotic therapy can reduce the risk of developing cerebrovascular accident in patients with myocardial infarction. It is likely that a decrease in the activity of subclinical inflammation after myocardial infarction will also reduce the risk of stroke, as was recently shown in the COLCOT study. Currently, it remains relevant to search for new knowledge about the risk factors for stroke, which complicated the course of myocardial infarction, which will allow developing more effective and personalized preventive measures in a patient with acute coronary syndrome.
, , Yu. I. Grinshtein, I. I. Gvozdev, , T. S. Mongush
Rational Pharmacotherapy in Cardiology, Volume 17, pp 16-22; doi:10.20996/1819-6446-2021-01-07

Abstract:
Aim. To study the relationship between the levels of synthesis of reactive oxygen species (ROS) by platelets and neutrophils in patients with coronary heart disease (CHD) before and after coronary artery bypass grafting (CABG), depending on sensitivity to acetylsalicylic acid (ASA). Material and methods. The study included 95 patients with coronary artery disease who are indicated for CABG surgery. The control group consisted of 30 healthy donors. The antiplatelet therapy was stopped for at least 5 days before CABG. In the postoperative period, from the first day, all patients were received 100 mg of an enteric form of acetylsalicylic acid (ASA). Resistance to ASA was determined at the level of platelet aggregation with arachidonic acid ≥20% by optical agregometry at least at one observation point: before CABG, on 1-3 day and on 8-10 day after surgery. We evaluated the spontaneous and induced lucigenin-dependent chemiluminescence (CL) of platelets (ADP induction) and neutrophils (zymosan induction) by the exit time to maximum intensity (Tmax), maximum intensity (Imax) and area (S) under the CL curve. Results. 70.5% sensitive (sASA) and 29.5% resistant (rASA) to ASA patients were revealed. Prior to CABG, in sASA patients, the Imax of spontaneous and zymosan-induced neutrophil CL and CL platelet activity was increased relative to control values. Tmax of spontaneous platelet CL, Imax and S under the ADP-induced platelet CL curve were lower in sASA patients, if to compare with rASA patients. On the 1st and 8-10th day after CABG in sASA patients, the CL indicators of neutrophil and platelet activity also remained elevated compared to control values. On the 1st day after CABG decreased levels of S under the spontaneous CL curve of neutrophils in rASA patients was established compared with sASA patients, and increased levels of Imax and S under the curve of induced neutrophil CL were detected in comparison with the control range. In rASA patients, the values of Tmax of spontaneous platelet CL decreased in relation to the values detected in the control group and sASA patients. On the 8–10th day after CABG, most indicators of spontaneous and zymosan-induced CL neutrophils in rASA patients were also increased compared to control values. In rASA patients a positive correlation of Imax-induced CL was found (r=0.83) on the 1st day after CABG and negative correlations of Tmax of spontaneous CL (r=- 0.75) and S under the curve induced CL (r=-0.70) on the 8-10th day were detected between platelets and neutrophils. Conclusion. In sASA patients with coronary heart disease before and after CABG, a high level of synthesis of superoxide radical by neutrophils and platelets was detected. The relationship between the levels of the synthesis of superoxide radical by neutrophils and platelets was found only after CABG in rASA patients. Increased synthesis of superoxide radical due to metabolic and regulatory relationships in neutrophils and platelets stimulates pro-inflammatory processes in coronary artery disease and determines the sensitivity of platelets to ASA.
Rational Pharmacotherapy in Cardiology, Volume 17, pp 56-61; doi:10.20996/1819-6446-2021-02-11

Abstract:
Aim. To compare clinical features, drug therapy and outcomes in patients with non-obstructive and obstructive coronary artery infarction. Material and methods. The study included 206 patients with a diagnosis of myocardial infraction (MI). According to the results of coronarography, patients were divided into two groups: 103 patients (group 1; MINOCA) did not have obstructive involvement coronary arterial (CA): in 67 (65%) of cases, there is no data for atherosclerotic coronary bed lesion, another 36 (35%) – have CA stenosis up to 50%. 103 patients (group 2) with MI and obstructive CA (MIOCA). The patients of the second group in 100% of cases underwent endoprosthesis of CA, the affection of which caused infraction. The second group was selected by the copy method comparatively to the first group. The analysis of clinical peculiarities, medication and outcomes was made in these groups of patients, in particular. Results and conclusions. The clinical “portrait” of patients with MI in nonobstructive and obstructive CA involvement did not differ significantly. Higher serum level of total cholesterol (5.6 [4.4;6.2] vs 5.1 [4.4;5.8] mmol/l р=0.04) and cholesterol of low-density lipoproteins (2.9 [2.2;3.5] vs 2.5 [2.1;2.9] mmol/l р=0,01), troponin [2.8 [0.7;15.0] vs 1.2 [0.1;7.7] ng/ml р=0.02) were identified in blood tests of MIOCA patients in the comparison with MINOCA group. Antero-lateral (р=0.02) and unspecified localization of MI (р=0.03) was more frequent in the MINOCA group. The differences in therapeutic approach were manifested in the more frequent prescription of double antiplatelet therapy: (99.0% vs 80.6% р< 0.01) in MIOCA patients. In the MINOCA group а more frequent prescription of dihydropyridine calcium channel blocking agents was registered (23.3% vs 2.9% р0.05), annual mortality (5.1% against 7.8%; p>0.05), and combined endpoint (6.8% against 10.7%; p>0.05). Conclusion. Despite the similarity of the clinical presentations of MI with obstructive and nonobstructive CA involvement in real clinical practice, there are differences in the pharmacotherapeutic approach in the management of these groups of patients. MINOCA is characterized by an unfavorable outcomes similar to MIOCA.
, I. A. Alyautdinova, S. N. Litvinova, A. V. Arablinskij, A. A. Kirichenko
Rational Pharmacotherapy in Cardiology, Volume 17, pp 124-132; doi:10.20996/1819-6446-2020-11-07

Abstract:
Arterial hypertension (AH) remains one of the main causes of disability and death worldwide, including in Russia. At the same time, the risks of coronary and cerebrovascular events increase in the presence of additional risk factors. The most common modifiable risk factors are metabolic disorders, including pre-diabetes, dyslipidemia, peripheral arterial atherosclerosis, and obesity, which also imposes certain features on the choice of optimal pharmacotherapy. Currently, the terminology of comorbid conditions continues to be discussed depending on their pathogenesis and the presence or absence of dominance of one disease over others, i.e. polymorbidity, comorbidity and multimorbidity. At the same time, “associative polymorbidity” is distinguished with a certain set of diseases that often occur in conjunction with each other with individual susceptibility of the body. One of the most common phenotypes of polymorbidity occurring in all age groups in both sexes is cardiometabolic, which is based on the formation of insulin resistance, sympathetic overactivity and chronic inflammation. This article provides a clinical example of the use of a fixed combination of angiotensin II receptor blocker telmisartan and calcium channel blocker amlodipine with the addition of an I1-imidazoline receptor agonist moxonidine in real clinical practice in a polymorbid cardiometabolic patient with target organ damage (left ventricular hypertrophy and microalbuminuria). High antihypertensive (favorable effect on 24-hour blood pressure, especially in the early morning) and organoprotective effectiveness of this combination, its possibilities in correcting additional risk factors (reduced heart rate, body weight and a positive effect on metabolic parameters), due to a synergistic effect on the central pathogenetic mechanisms of hypertension and obesity – insulin resistance and sympathetic overactivity.
E. I. Fomicheva, , , , E. L. Dadali, O. M. Drapkina
Rational Pharmacotherapy in Cardiology, Volume 17, pp 105-110; doi:10.20996/1819-6446-2021-01-05

Abstract:
Friedreich's disease is a hereditary neurodegenerative multiple organ disease, primarily affecting the most energy-dependent tissues (cells of the nervous system, myocardium, pancreas), the lesion of which is characterized by progressive ataxia, dysarthria, dysphagia, oculomotor disorders, loss of deep tendon reflexes, pyramid signs, diabetes mellitus, visual impairment. Friedreich's ataxia is the most common of all hereditary ataxias; nevertheless, this disease is considered orphan. By its pathogenesis, Friedreich's disease is mitochondrial ataxia, caused by a deficiency in the transcription of the FXN gene, leading to a decrease in the synthesis of the frataxin protein. Frataxin is a protein associated with the inner mitochondrial membrane, which in turn is involved in the formation of iron-sulfur clusters, the lack of which leads to a decrease in the production of mitochondrial ATP, an increase in the level of mitochondrial iron and oxidative stress. The basis of the clinical picture of Friedreich's disease is ataxia of a mixed (sensitive and cerebellar) nature. The steady and gradual progression of neurological symptoms significantly affects the quality of life of patients and is most often the leading reason for seeking medical attention. However, the prognosis is primarily due to the involvement of cardiac tissue in the pathological process. The main causes of death in patients with Friedreich's ataxia are severe heart failure and sudden cardiac death due to cardiomyopathy. The overwhelming majority of foreign and domestic publications on Friedreich's ataxia are devoted to the neurological manifestations of this disease, and little attention is paid to this problem in the cardiological scientific and practical society. The purpose of this review is to provide up-to-date information on modern methods of diagnosing myocardial damage at various stages of Friedreich's disease.
A. V. Savinova, V. S. Dobrodeeva, , R. F. Nasyrova, N. A. Shnayder
Rational Pharmacotherapy in Cardiology, Volume 17, pp 146-152; doi:10.20996/1819-6446-2021-01-04

Abstract:
Dabigatran etexilate is a prodrug of dabigatran, a oral direct inhibitor of thrombin. Pharmacokinetics of dabigatran etexilate doesn’t have the disadvantages of vitamin K antagonists. However, pharmacokinetics and pharmacogenetics of dabigatran are variable. This can affect both effectiveness and safety of anticoagulant therapy. It is considered that CES1 enzyme and P-glycoprotein (CES1 and ABCB1 genes accordingly) play important role in pharmacokinetics of dabigatran etexilate. UDP-glucuronosyltransferase enzymes UGT2B15, UGT1A9, UGT2B7 (UGT2B15, UGT1A9, UGT2B7 genes accordingly) take part in the metabolism of active dabigatran. Presence of these gene’s single-nucleotide variants (SNV) can affect effectiveness and safety of dabigatran etexilate usage. The goal of this review is analysis of associated researches of SNV genes CES1 and ABCB1 and search for new candidate genes that reveal effectiveness and safety of dabigatran etexilate usage. Materials and methods. The search for full-text publications in Russian and English languages containing key words “dabigatran etexilate”, “dabigatran”, “pharmacokinetics”, “effectiveness”, “safety” was carried out amongst literature of the past twenty years with the use of eLibrary, PubMed, Web of Science, OMIM data bases. Pharmacokinetics and pharmacogenetics of dabigatran etexilate are considered in this review. The hypothesis about UDP-glucuronosyltransferase enzymes influence on dabigatran metabolism was examined. Nowadays more than 2000 SNV CES1 and ABCB1 genes are identified, but their potential influence on pharmacokinetics of dabigatran etexilate and its active metabolite (dabigatran) in clinical practice needs to be further researched. Role of SNV UDP-glucuronosyltransferase genes (UGT2B15, UGT1A9, UGT2B7) in dabigatran’s effectiveness and safety is not explored enough. However, UGT2B15 gene can be a potential candidate gene for research on safety of this drug.
, Y. V. Lukina, E. D. Zharkova,
Rational Pharmacotherapy in Cardiology, Volume 17, pp 99-104; doi:10.20996/1819-6446-2021-01-06

Abstract:
The new coronavirus infection (COVID-19) pandemic and the subsequent quarantine measures, particularly home isolation of the population, could have seriously affected the quality of pharmacotherapy and adherence to it by patients with chronic non-communicable diseases. Aim. To assess the dynamics of adherence to pharmacotherapy by patients with stable coronary artery disease (SCAD) in self-isolation during the COVID-19 pandemic. Material and methods. To accomplish the aim of the study, we selected 39 patients with SCAD who previously completed the ALIGN study, the purpose of which was to align patients’ medical therapies according to current clinical guidelines. From May 05, 2020, to May 14, 2020, a telephone survey was conducted of 39 patients with SCAD (37, 94.8%) males, mean age 67.6±8.5 years). After one year of participation in the ALIGN study, 87.1% of the patients were adherent to their prescribed pharmacotherapy. Adherence (overall and to specific medications) was assessed by means of the original adherence scale, which made it possible to identify violations in taking medications (non-adherence to the intake regime or discontinued intake of medications), and the main reasons for adherence violation were established. Adherence registered during the telephone survey at the time of the COVID-19 pandemic was compared to that obtained during the last time the patient participated in the ALIGN study. Results. During the period of home isolation, a substantial decline in the adherence of patients to pharmacotherapy was revealed. The percentage of adherent patients decreased from 87% to 54% due to an increase in the number of patients who stopped taking several or all of the recommended drugs during home isolation (p=0.024). The overall rate of adherence during the COVID-19 pandemic appeared to be even worse than before the start of the ALIGN study. A comparative analysis of subgroups with and without a decline in adherence revealed a trend suggesting that higher patient education (p=0.067) or previous percutaneous coronary intervention (p=0.063) can be considered a protective factor associated with fewer violations in adherence during the COVID-19 pandemic. Analysis of adherence to specific drugs showed that during self-isolation there was a decrease in adherence to antiplatelet drugs (p=0.047) and to statins (p=0.055). Adherence to beta-blockers, renin-angiotensin-aldosterone system inhibitors and dihydropyridine calcium antagonists remained unchanged. Conclusion. In patients with SCAD during the period of home isolation in the COVID-19 pandemic and associated difficulties in contacting the attending physician, there was a decline in adherence and an increase in the number of patients who stopped taking several or all prescribed drugs.
, S. B. Fitilev, , I. I. Shkrebniova
Rational Pharmacotherapy in Cardiology, Volume 17, pp 29-35; doi:10.20996/1819-6446-2020-16-08

Abstract:
Aim. To study predictors of primary care physician adherence to guideline-recommended pharmacotherapy of stable coronary artery disease. Material and methods. This pharmacoepidemiologic cross-sectional study was conducted in primary care setting of Moscow. 805 patients (mean age 68.9±9.9 years, males 51.4%) with established stable coronary artery disease (SCAD) were included. Demography, medical history, prescribed pharmacological treatment data were obtained. Physician adherence to guideline-recommended pharmacotherapy (GRP) of SCAD was evaluated based on the Class I guideline recommendations. Pharmacotherapeutic guideline adherence index (PGAI) was introduced as composite quality indicator, calculated in line with “all-or-none” rule and in regard with documented contraindications. To search for predictors of adherence the patient population was divided in two groups by level of physician adherence measured by PGAI. Statistical analysis was performed by IBM SPSS Statistics 16.0, the level of statistical significance was set at p Results. The prescription rates of essential drug therapies of SCAD (regarding contraindications) were quite adequate: beta-blockers/calcium channel blockers – 90,1%, acetylsalicylic acid/clopidogrel/oral anticoagulants – 95,7%, statins/ezetimibe – 86,3%, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers – 87,6%. 82,9% (n=667) of patients were prescribed treatment for SCAD in compliance with the guidelines. Suboptimal pharmacotherapy was identified in 17,1% (n=138) of patients. These groups were similar in sex distribution (males 50,4 vs. 56,5%; p=0,188). Mean age tended to be lower in GRP adherent group (68,5±9,9 vs. 70,6±10,0 years; p=0,052). Bivariable analysis showed that good adherence to guideline-recommended pharmacotherapy was associated with higher prevalence of stable angina (66,4 vs. 53,6%; p=0,004), arterial hypertension (93,3 vs. 79,7%; p Conclusion. Primary care cardiologist adherence to guideline-recommended pharmacotherapy of SCAD was satisfactory evaluated as 82,9% by composite indicator PGAI. Arterial hypertension, heart failure, dyslipidemia и revascularization were predictors of better physician adherence. History of myocardial infarction and older age were risk factors of non-adherence. Identification of patient-related factors associated with underperformance may facilitate tailoring quality improvement interventions in primary care of coronary patients.
S. A. Davitashvili, D. V. Nebieridze, N. M. Akhmedzhanov, A. S. Lishuta, A. S. Safaryan
Rational Pharmacotherapy in Cardiology, Volume 17, pp 49-55; doi:10.20996/1819-6446-2020-11-10

Abstract:
Aim. To study adherence to recommended treatment, additional clinical and economic benefits of a titration-free statin therapy regimen. Material and methods. Ambulatory patients (n=300) with a high or very high risk of hypercholesterolemia who have indications for statin treatment for primary or secondary prevention of cardiovascular diseases is included in a non-randomized trial. Patients are divided into 2 groups. Group 1 had a titration regimen of statins in accordance with current recommendations (group 1A [n=50] – primary cardiovascular prevention; group 1B [n=100] – secondary cardiovascular prevention). Group 2 received a titration-free statin regimen in fixed doses (group 2A [n=50] – primary cardiovascular prevention; group 2B [n=100] – secondary cardiovascular prevention). Patients were prescribed atorvastatin (10-80 mg/day) or rosuvastatin (10- 40 mg/day). Group 1 patients had visits to the doctor after 1, 3, 6 and 12 months from the start of statin use, group 2 patients after 3 and 12 months. Treatment adherence, effects on surrogate and hard endpoints, and cost-effectiveness of the two statin regimens were evaluated. Results. The target level of low-density lipoprotein cholesterol (LDL-C) after 12 months in group 2 was achieved in 56.4% of patients versus 53.4% in group 1. The average level of LDL-C decreased by 1.84±0.44 mmol / l in group 2 versus a decrease of 1.61±0.47 mmol / L in group 1. The costeffectiveness ratio was 9658.72 rubles in group 2 versus 8341.73 rubles in group 1 for a 1 mmol / l LDL-C level decrease in 1 patient within a year. An increase in annual costs per patient in group 2 compared with group 1 by 75.76 rubles reduced the relative risk of developing a combined endpoint by 1% per year. Conclusion. The use of a titration-free statin treatment regimen allowed us not only to more effectively control of LDL-c levels in patients with high and very high cardiovascular risk compared to the traditional statin therapy regimen, but also to obtain economic advantages in patients with high and very high cardiovascular risk.
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