Rational Pharmacotherapy in Cardiology

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ISSN / EISSN : 1819-6446 / 2225-3653
Published by: Stolichnaya Izdatelskaya Kompaniyaizdat (10.20996)
Total articles ≅ 1,604
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, D. A. Shatsky, N. V. Shikh, T. B. Andrushchyshina, M. V. Lukina, A. A. Kachanova, , , N. P. Denisenko, E. A. Grishina, et al.
Rational Pharmacotherapy in Cardiology, Volume 17, pp 570-575; https://doi.org/10.20996/1819-6446-2021-08-12

Abstract:
Aim. The aim of the study was to evaluate the efficacy and safety of ketoprofen as an analgesic therapy in patients with CYP2C9*2 (430C>T) r s179985 and CYP2C9*3 (1075A>C) rs1057910 gene polymorphisms after cardiac surgery. Material and methods. The study included 90 patients. Postoperative analgesia was perfomed by ketoprofen 100 mg intramuscularly twice daily. The evaluation of pain was determined daily by Numeric Rating Scale for 5 days after cardiac surgery. The safety of ketoprofen was determined by assessing the severity of gastroenterological symptoms using the Gastrointestinal Symptom Rating Scale questionnaire and determining the frequency of episodes of acute kidney injury. The material for DNA was venous blood. To determine the single nucleotide genetic polymorphisms CYP2C9*2 (430C>T) rs179985 and CYP2C9*3 (1075A>C) rs1057910, the real-time polymerase chain reaction was used. Results. In patients with the AA genotype of CYP2C9*3 polymorphism, the intensity of pain on the numeric rating scale scale (points) was significantly higher than in patients with the AC genotype: 7 [6; 8] vs 6 [5; 6] (р=0,003), 7 [6; 8] vs 6 [5; 6] (р=0,04), 6 [5; 7] vs 5 [4; 5] (р=0,04), 5 [3; 6] vs 3 [3; 4] points (р=0,02) on days 1, 2, 3 and 5 of the postoperative period, respectively. The severity of gastroenterological symptoms was higher in patients with a heterozygous CT genotype for the allelic variant CYP2C9*2 than in patients with a wild CС genotype and amounted to 19 [19; 22] vs 18 [16; 20] points, respectively, (p=0,04). The distribution of genotypes for CYP2C9*2 polymorphisms and CYP2C9*3 polymorphisms between the groups of acute renal injury did not differ significantly. Conclusion. Associations of polymorphisms CYP2C9*3 with a lower intensity of pain syndrome and CYP2C9*2 with a greater severity of gastroenterological symptoms were revealed.
Rational Pharmacotherapy in Cardiology, Volume 17, pp 606-611; https://doi.org/10.20996/1819-6446-2021-08-06

Abstract:
The review contains actual data on possible approaches aimed at improving the prognosis in a special category of patients with extremely high cardiovascular risk, as well as in patients with recent acute coronary syndrome combined with comorbidity, including multifocal atherosclerosis. Currently, there are no class I recommendations for such patients aimed at reducing the risk of adverse cardiovascular events. It is suggested that suppression of inflammation may be a new therapeutic goal in this category of patients. Given the importance of inflammation in the development and course of atherosclerosis, in recent years there have been repeated attempts to influence the various components of the pro-inflammatory cascade involved in atherogenesis, but not all of them have been successful. Special attention is given to the anti-inflammatory effects of colchicine, a drug that can improve cardiovascular outcomes in patients with proven atherosclerosis. The review provides numerous pathogenetic and clinical evidence for the effectiveness of colchicine in patients with various manifestations of atherosclerosis. It is concluded that colchicine is the most promising anti-inflammatory drug that can improve the outcome of cardiovascular diseases. Thus, there is a need to initiate new clinical trial protocols aimed at studying the anti-inflammatory potential of this drug in patients with extreme cardiovascular risk.
K. S. Karaganov, O. A. Slepova, A. S. Lishuta, N. I. Solomakhina, Yu. N. Belenkov
Rational Pharmacotherapy in Cardiology, Volume 17, pp 557-563; https://doi.org/10.20996/1819-6446-2021-08-03

Abstract:
Aim. To study the mid-term effects of enhanced external counterpulsation (EECP) in the structural and functional parameters of blood vessels, exercise tolerance and quality of life indicators in patients with verified coronary artery disease (CAD). Material and methods. Patients (n=70) with verified stable CAD (angina pectoris class II-III) complicated by chronic heart faillure class II-III (NYHA) were included in the study. Data from 65 patients (48 to 74 years old; 45 men and 20 women) are included in the final analysis. All patients had a course of EECP (35 hours procedures with a compression pressure of 220-280 mm Hg). All patients at baseline, 3 and 6 months later had a 6 walk minute test (6WMT), an assessment of the clinical status, quality of life of patients (Minnesota Living with Heart Failure Questionnaire, SF-36). Computer nailfold video capillaroscopy, photoplethysmography with pulse wave recording and contour analysis, applanation tonometry to assess central aortic systolic pressure and radial augmentation index were performed to assess the structural and functional state of large and microcirculatory vessels. Results. Significant improvement in exercise tolerance both after 3 and after 6 months (increase in distance in 6WMT by 44.6% after 3 months and 34.3% after 6 months, p <0.05), improved quality of life (increased overall score on the SF-36 questionnaire from 50.3±8.1 to 59.8±8.8, p<0.05), an increase in the left ventricular ejection fraction were found. Significant improvement in indicators showing the function of the endothelium of both large vessels (phase shift: from 5.6 [2.45; 7.3] to 6.8 [3.1; 8.1] m / s) and microcirculatory vessels (occlusion index: from 1.51 [1.21; 1.7] to 1.66 [1.2; 1.9]), as well as a decrease in functional disorders of the capillary bed of the skin (% of perfused capillaries, density of the capillary network in the test with reactive hyperemia) were found after 3 months. However, after 6 months, there were no significant changes in these parameters compared to the baseline value. No significant change in indicators showing structural remodeling of both large vessels and microcirculatory vessels was found. Conclusion. The positive effect of the EECP course on the functional status (exercise tolerance) and quality of life in patients with stable coronary artery disease complicated by chronic heart faillure was found both after 3 and 6 months. Positive dynamics of the functional state of large vessels and microvasculature was found only after 3 months.
, , A. A. Kornilova, , , A. V. Naminov
Rational Pharmacotherapy in Cardiology, Volume 17, pp 537-543; https://doi.org/10.20996/1819-6446-2021-08-15

Abstract:
Aim. Evaluation of various methods for determining the effectiveness of aspirin therapy and aspirin resistance in patients with cerebrovascular disease (CVD) depending on the presence of type 2 diabetes mellitus (T2DM). Materials and methods. The prospective study included 78 patients with various manifestations of CVD. All patients received acetylsalicylic acid (ASA) 75 mg daily. Along with a comprehensive clinical examination, a laboratory assessment of platelet function with the usage of Born method with aggregometer, a detailed biochemical blood test (including the determination of the small subunit of low density lipoprotein [s-LDL]), as well as therapeutic drug monitoring of salicylates were performed on a gas chromatograph-mass spectrometer. Results. In 53% of cases, the absence or insufficiency of the effect of ASA on platelet aggregation was noted. Two subgroups were separately identified: with T2DM; (n=40) and without T2DM (n=38). Insufficient effect of the drug on platelet aggregation characteristics were observed in 65% of patients with T2DM and in 38% without T2DM. The differences were revealed between the groups in triglycerides, s-LDL, glycemic and glycated hemoglobin (p <0.05). In the group of patients with T2DM, the median ASA concentration was 0.01 [0; 0.32] μg/ml, and salicylic acid (SA) – 0.20 [0; 0.39] μg/ml, while in patients without T2DM higher values were noted: ASA 0.29 [0.15; 0.55] μg/ml, SA – 0.33 [0.05; 0.73] μg/ml. A decrease in the concentration of ASA was associated with an increase in the level of ADP-induced platelet aggregation. There was an increase in the levels of ADPand adrenaline-induced platelet aggregation with a decrease in the concentration of ASA (p=0.004) and SA (p=0.006). Therapeutic drug monitoring revealed a more significant decrease in ASA level in T2DM than in the comparison group (p=0.025). Conclusion. It is advisable to monitor aspirin therapy both with the assessment of platelet aggregation and with therapeutic drug monitoring. The relationship between the level of ASA and SA in the blood plasma and the functional activity of platelets was confirmed. The presence of T2DM is associated with a decrease in the concentration of ASA and aspirin resistance detected in therapeutic drug monitoring.
, V. A. Otdelenov, M. D. Nigmatkulova, , , O. D. Konova, L. P. Yashina, A. M. Cherkashov,
Rational Pharmacotherapy in Cardiology, Volume 17, pp 544-551; https://doi.org/10.20996/1819-6446-2021-08-10

Abstract:
Aim. To study the structure of anticoagulant prescription in a general hospital to identify trends and contributing factors. Materials and methods. The study was conducted in an urban general hospital. According to retrospective retrieval from electronic health records, total 17,129 patients received anticoagulants from 2008 to 2018. Formal appropriateness of oral anticoagulants (OАС) prescriptions for 6,638 patients with atrial fibrillation (AF) was analyzed with CHA2-DS2-VASc score. Results. Appearance of recommendations for the direct oral anticoagulants (DOAC) prescription in clinical guidelines for venous thromboembolism (VTE) and AF management contributed to steady increase in the DOAC taking and decrease in the proportion of warfarin prescription. From 2011 to 2018, the proportion of patients with DOACs prescription increased from 1.7% to 81.5%. The most common indications for anticoagulant were ischemic stroke prevention in AF and VTE with mean rate 75.3% and 23.2%, respectively for the 2011-2018 period. Steady increase in low-molecular-weight heparin (LMWH) prophylactic prescriptions was also shown (Chi-square for linear trend=1340, df=1, p<0.0001). Since 2014, the prescription of LMWH in prophylactic doses increased dramatically, probably related to implementation of computerized decision support system (CDSS) for VTE prevention in the hospital. Conclusion. The study showed that in a general hospital anticoagulants were prescribed in 19% of hospitalized patient. Not only the new clinical recommendations based on the results of the recent studies on anticoagulants efficacy and safety (external factors), but also implementation standard operating protocols and CDSS, providing physicians current information about the relevant clinical recommendations (internal changes), could influence the appropriateness of anticoagulants prescription.
Rational Pharmacotherapy in Cardiology, Volume 17, pp 576-583; https://doi.org/10.20996/1819-6446-2021-08-02

Abstract:
Aim. Development, testing and validation of the original questionnaire “Adherence Scale” (AS) in the PRIORITY and ANTEY observational studies (OS). Materials and methods. The OS PRIORITY assessed adherence to statins in 298 patients with high and very high cardiovascular risk for 3 months. The OS ANTEY assessed adherence to oral anticoagulants in 201 patients with non-valvular atrial fibrillation for 1 year. Adherence was assessed using the original AS questionnaire, for which external validation was performed (with the calculation of the Cohen's Kappa coefficient). The reference methods were the validated questionnaire and direct medical interview. And internal validation was performed (consistency of questions on the AS using Spearman's correlation analysis). The sensitivity, specificity (ROC analysis) and retest reliability of the adherence scale (Cronbach's alpha) were also determined. Results. In the OS PRIORITY Cohen's kappa for the AS and the reference method of direct medical survey was 0.76 (high consistency), and for the AS and the reference method of the validated questionnaire=0.28 (low consistency). High internal consistency of the questionnaire questions (correlation coefficient=0.78, p<0.0001) confirms the internal validity of the adherence scale. Evaluation of the main characteristics of the modified AS in the OS ANTEY showed high consistency between the results of the AS and the validated questionnaire: Cohen's kappa=0.94 (high external validity of the AS). The retest reliability of the AS was 0.76 (Cronbach's alpha). The internal consistency of the questionnaire was confirmed by a strong and statistically significant correlation between the test questions: Spearman's correlation coefficient=0.80, p<0.0001. The sensitivity of the test, determined using the ROC analysis, was 89%, and the specificity was 62%. Conclusion. The developed and tested new original questionnaire (modified version) – the AS – showed high indicators of reliability, validity and sensitivity. This ensures its reliability and ease of use for assessing various types of adherence and determining the leading factors of non-adherence, and also allows its use in scientific studies and clinical practice.
V. I. Petrov, N. V. Rogova, T. N. Кuzmina, A. S. Lishuta
Rational Pharmacotherapy in Cardiology, Volume 17, pp 552-556; https://doi.org/10.20996/1819-6446-2021-08-16

Abstract:
Aim. To study changes in epithelialization of diabetic foot ulcers and parameters of laser Doppler flowmetry (LDF) in patients with diabetic foot syndrome (DFS) and atrial fibrillation (AF) during complex therapy with the addition of direct oral anticoagulants (DOAC). Material and methods. An open-label comparative randomized study in parallel groups was performed. Patients with neuroischemic DFS and persistent FA without previous anticoagulant therapy were randomized into two groups: combination therapy for DFS and rivaroxaban (group 1; n=24) or combination therapy for DFS and dabigatran (group 2; n=22). Changes in local status in diabetic foot ulcers, coagulogram parameters and LDF were studied at 4 and 12 weeks. Results. Complete epithelialization of diabetic foot ulcers after 12 weeks was found in 14 (58.3%) patients in group 1, and in 10 (45.4%) patients in group 2. Statistically significant improvements in LDF parameters were found in both groups in both groups: an increase in the microcirculation index by 53.5% (p=0.02), pulse wave by 124.0% (p=0.003), respiratory wave by 59.4% (p=0.007) was found in group 1. An increase in the microcirculation index by 48.5% (p=0.02), pulse wave by 73.1% (p=0.003), respiratory wave by 47.1% (p=0.03) were found in group 2. Conclusion. Positive statistically significant changes in epithelialization of diabetic foot ulcers and LDF parameters were found in patients with DFS and AF during 12 weeks of complex therapy with the addition of DOACs (rivaroxaban and dabigatran). Further research for DOACs in DFS patients is needed.
A. V. Panov
Rational Pharmacotherapy in Cardiology, Volume 17, pp 628-637; https://doi.org/10.20996/1819-6446-2021-07-02

Abstract:
Comprehensive protection of a patient with atrial fibrillation (AF) should not only reduce the risk of stroke and systemic embolism, but also reduce the risk coronary events and ensure high adherence to treatment. In accordance with consensus document issued by the European Heart Rhythm Association, European Society of Cardiology, European Association of Percutaneous Cardiovascular Interventions, as well as with other recent Russian Society of Cardiology Guidelines, the management of antithrombotic therapy of patients with AF undergoing percutaneous coronary intervention (PCI) requires that multiple and interconnected issues. The review article addresses questions about duration of initial triple antithrombotic therapy (TAT), selection of P2Y12 inhibitor, choice of oral anticoagulant to be combined with antiplatelet therapy, intensity of oral anticoagulation throughout combination therapy, and choice of oral anticoagulant for indefinite therapy. In general, it is recommended to refuse the routine use of TAT for most patients. Accordingly, for patients who need both anticoagulant and antiplatelet therapy, it is strongly recommended that the default strategy after recent PCI is a double antithrombotic therapy consisting of an anticoagulant and one antiplatelet, preferably from the group of P2Y12 inhibitors. When conducting combined antithrombotic therapy, preference should be given to clopidogrel compared to other, more powerful P2Y12 inhibitors and direct oral anticoagulant (DOAC) instead of vitamin K antagonists. The primary choice of DOAC in patients with AF who have undergone PCI should be carried out taking into account such factors as individual risk of stroke and bleeding, adherence to treatment, concomitant diseases, pharmacological characteristics and evidence base of a specific DOAC, taking other medications, etc. The pharmacokinetic features of rivaroxaban, which create the possibility of its single administration, the evidence base for reducing coronary risks in various variants of the course of coronary heart disease, determines the special positions of the drug for the comprehensive protection of patients with AF after PCI.
S. R. Gilyarevsky
Rational Pharmacotherapy in Cardiology, Volume 17, pp 584-593; https://doi.org/10.20996/1819-6446-2021-08-01

Abstract:
The article is devoted to the discussion of the problems of assessing the quality of observational studies in real clinical practice and determining their place in the hierarchy of evidence-based information. The concept of “big data” and the acceptability of using such a term to refer to large observational studies is being discussed. Data on the limitations of administrative and claims databases when performing observational studies to assess the effects of interventions are presented. The concept of confounding factors influencing the results of observational studies is discussed. Modern approaches to reducing the severity of bias in real-life clinical practice studies are presented. The criteria for assessing the quality of observational pharmacoepidemiological studies and the fundamental differences between such studies and randomized clinical trials are presented. The results of systematic reviews of real-life clinical trials to assess the effects of direct oral anticoagulants are discussed.
, R. I. Stryuk, A. A. Golikova,
Rational Pharmacotherapy in Cardiology, Volume 17, pp 638-641; https://doi.org/10.20996/1819-6446-2021-08-13

Abstract:
The main stages of the creative path of the scientist with a world-famous, professor, the Honored Worker of Science of the Russian Federation, Academician of the Russian Academy of Sciences Alexey Petrovich Golikov are presented in the article.
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