ORIGINAL STUDIES 
Aim. To compare safety of new class III antiarrhythmic drug Refralon with direct current cardioversion (DCC) in patients with persistent atrial fibrillation (AF). Material and methods. 60 patients with persistent AF were randomized to groups of DCC (n=30) and pharmacologic conversion (PCV; n=30). There were no significant differences in age, sex, AF duration, concomitant cardiovascular diseases, CHA2DS2-VASc score and echocardiographic parameters between the groups compared. Initial assessment excluded contraindications to restore sinus rhythm (SR). In DCC group two attempts using biphasic synchronized shocks of 150 J and 170 J were performed. In PCV group patients received up to three subsequent intravenous injections of Refralon 10 μg/kg (maximal dose 30 μg/kg). Results. There were no mortality, stroke, transient ischemic attack, ventricular arrhythmia, asystole longer than 3,0 sec (primary safety criteria) in both groups. Prolongation of QT interval longer than 500 ms observed in 1 of 30 patients (3,3%) in DCC group and in 7 of 30 patients (23,3%) in PCV group. 2 patients (one patient in each group; 3,3%) developed asymptomatic bradycardia after conversion to SR that resolved spontaneously within 30 minutes. 95% confidence interval (95%CI) for secondary safety criteria is [0,02-0,38] for QT prolongation and [-0,04-0,04] for bradycardia. Conclusion. Safety of PCV is noninferior to DCC in patients with persistent AF in terms of primary safety criteria and bradyarrhythmias. More frequent QT interval prolongation to values >500 ms observed in PCV group points to necessity of precautions with use of the drug.
Aim. To study the prescribed drug therapy, as well as adherence to it in patients with acute coronary syndrome (ACS) in real clinical practice within a year after the index event. Material and methods. The study included 327 patients who were in hospital treatment with ACS: 199 patients (60.9%) with unstable angina (UA) and 128 (39.1%) – with acute myocardial infarction (AMI). The prescribed treatment and adherence to therapy were evaluated within 12 months after the coronary event. Therapy prescribed to patients was compared with current clinical guidelines for the treatment of patients with ACS. Results. 67% of patients completed the clinical study Adherence to prescribed medication within 12 months after ACS was maximal for ACE inhibitors/angiotensin receptor blockers (83.6%), dual antiplatelet therapy (79.9%) and β-blockers (78.1%), and minimal for lipid-lowering drugs (statins; 61.6%). A significant decrease in adherence was revealed in 6 and 12 months from the initiation of therapy. Significantly higher level of adherence to DAT was found in patients with AMI compared with patients with UA (p<0.05). When analyzing the frequency of occurrence of endpoints, it was found that patients who did not adhere to treatment significantly more often had hospitalizations due to UA (15.1% vs 7.4%; p<0.05), AMI (16.9% vs 8.1%; p<0.05), death from cardiovascular causes (13% vs 10.4%; p<0.05). Conclusion. Therapy prescribed at the outpatient stage in patients with ACS in the Rostov Region corresponds to the modern clinical recommendations. Six months after hospital discharge adherence to drug therapy in patients is reduced, which requires more careful outpatient monitoring during this period. In patients who are not adherent to treatment, cardiovascular complications are significantly more frequent.
Aim. To study the frequency of oral anticoagulants (ОАС) prescription for patients with atrial fibrillation (AF) after myocardial infarction (MI). Material and methods. The study includes 106 patients (60 men, 55.6%) with a previously established diagnosis of AF, who were on hospital treatment in the period 2016-2017 years in one of the university hospitals of the city and having at the time of discharge from the hospital the final diagnosis of МI. The median age was 70.0 (61.0;78.0) years. Patients with the first and only paroxysm of AF were excluded from the analysis and all further calculations were performed for 104 patients. In 64 (60.2%) of cases, AF was presented by paroxysmal form, while in 2 (1.9%) cases this paroxysm was the first and only, in 20 (18.9%) cases – persistent AF and in 20 (18.9%) – pernanent. Results. While assessing the risk of thromboembolic complications on the CHA2DS2-VASc scale, the median score for all patients was 5.0 (4.0;6.0) points. While assessing the risk of hemorrhagic complications on the HAS-BLED scale, the median score for all patients was 2.0 (2.0;3.0) points. HAS-BLED≤2 value had 71 (68.3%) patients, HAS-BLED≥3 – 33 (31.7%). Only one antiplatelet agent was prescribed to 4 (3.8%) patients. Aspirin was the only antiplatelet agent in 3 cases and clopidogrel – in one case. In 80 (76.9%) cases, patients were prescribed dual antiplatelet therapy, in 17 (16.3%) – ОАС therapy, among which 7 (6.7%) cases – a triple antithrombotic therapy (ATT), 9 (8.7%) cases – a double ATT (ОАС+ antiplatelet agent) and 1 (1.0%) case – a monotherapy. Among all cases of OAC prescription warfarin was prescribed in 11 (64.7%) cases and rivaroxaban – in 6 (35.3%). Conclusion. In real clinical practice, the prescription or refusal of ОАС occurs without taking into account the risk of thromboembolic and hemorrhagic complications according to appropriate scales.
NOTES FROM PRACTICE 
ASSOCIATED PROBLEMS OF CARDIOLOGY 
PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH 
Aim. To evaluate the structure of combined cardiovascular diseases, drug treatment and observation of patients with a history of stroke in the framework of prospective outpatient registries. Material and methods. The study was conducted based on 3 outpatient clinics of Ryazan city. Patients with a history of acute cerebrovascular accident (ACVA) of any remoteness (AR) were included into ACVA-AR outpatient registry (n=511). Patients who had visited the outpatient clinics for the first time (FT) after cerebral stroke (n=475) were included into the ACVA-FT outpatient registry. The structure of the cardiovascular diseases (CVD), compliance with the clinical recommendations of the prescribed and received drug therapy were evaluated. The proportion of patients with dispensary observation for CVD, using preferential drug provision was determined. Results. A combination of 2 or more CVDs was found in 84.4% and 82.5% of cases, and severe cardiovascular multimorbidity (3-4 CVDs) – in 69% and 64% of cases, respectively, in ACVA-AR and ACVA-FT registers. Compliance with the clinical guidelines prescribed and received drug therapy was insufficient at the outpatient stage. Necessary prescription of drugs with a proven beneficial effect on the prognosis were observed significantly more frequent in the ACVA-FT registry, compared to the ACVA-AR registry at the enrolling stage of the study (p<0.05): statins for stroke – 50.1% vs 25.2%; statins for coronary heart disease (CHD) – 47.2% vs 27.9%; antiplatelet agents for CHD without atrial fibrillation – 65.6% vs 54.3%; anticoagulants for atrial fibrillation – 17.7% vs 9.3%; beta-blockers for heart failure 43.5% vs 33.1%, respectively. After 2-3 years of the follow-up frequency of prognostically significant prescriptions in patients of the compared registries were not significantly different, except prescriptions for statin therapy (47.6% vs 21.3%, respectively). The prognostically significant prescriptions during the enrolling stage in ACVA-AR and ACVA-FT registries occurred in 44.4% and 54% of the total number of proper prescriptions, and in the long-term follow-up period – in 55% and 57%, respectively; and the dispensary observation coverage was only 35.0% and 31.8%, respectively. According to patient contact only 21-24% of patients used the system of preferential drug provision at the stage of inclusion into the registers, and after 2-3 years of follow-up – 1.5-2 times less (12-14%). Conclusion The results of the study REGION found the presence of cardiovascular multimorbidity in 83% of patients with a history of stroke, insufficient quality of prescribed drug therapy in the out-patient clinic, especially in the ACVA-AR registry. The quality of medical treatment of patients improved within 2-3-year follow-up after the reference visit to out-patient clinic, but not sufficiently. Increase in dispensary observation coverage and optimization of the system of preferential drug provision are also important reserves for improving the quality of treatment of patients with a history of stroke, as well as prevention of cardiovascular complications.
PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY 
INNOVATIVE CARDIOLOGY 
POINT OF VIEW 
The review focuses on the use of oral anticoagulants in fragile elderly patients. The issues of prevalence and diagnosis of senile asthenia syndrome or “fragility”, as well as its effects on the risks of thrombosis, bleeding and death, are discussed. The evidence base, which is quite limited, for the participation of fragile elderly patients in randomized controlled trials and real clinical practice trials with direct oral anticoagulants is presented. Nevertheless, one of the studies of real clinical practice showed that only therapy with rivaroxaban (out of three direct oral anticoagulants) compared with warfarin reduced the risk of stroke/systemic embolism and ischemic stroke alone in fragile elderly patients with atrial fibrillation after 2 years of observation.
The article discusses the current prevalence of hypercholesterolemia in everyday clinical practice in patients of different risk categories and approaches to its correction in the most frequently used clinical guidelines. High prevalence of hypercholesterolemia in practical health care with little change over time is shown. The existing problems of the practical implementation of the principles of a healthy lifestyle as the basis for reducing cardiovascular risk and possible solutions are described. Attention is focused on a low number of patients taking statins, and even less – reaching recommended target cholesterol levels. It is emphasized the validity of lower, compared to previous, target cholesterol levels in National recommendations on the correction of dyslipidemia in patients with proven atherosclerosis-related cardiovascular diseases as well as the feasibility in some cases of combined lipidlowering therapy (statins in combination with intestinal cholesterol absorption blockers, PCSK9 inhibitors, high doses of ethyl eicosopentaenoic acid). It is commented the need to prescribe statins in persons older than 75 years, but with a careful approach. Particular attention is paid to the use of statins in the primary prevention of cardiovascular complications. The validity of prescribing fixed moderate doses of statins for this purpose is discussed, which is both scientifically based and more realistic in practical terms.
The aim of this review was to present the recently published results of ODYSSEY OUTCOMES trial and discuss the clinical perspective of these data. Patients with acute coronary syndrome are at very high risk of recurrent ischemic cardiovascular complications, especially during the first year after the event. The use of high-intensity statin therapy in this group of patients does not always lead to the achievement of target levels of atherogenic lipoproteins. PCSK9 inhibitors, administered in addition to statins, can provide additional reduction of low-density lipoprotein cholesterol, which leads to further improvements of outcomes in patients with atherosclerotic cardiovascular disease. According to the latest results from ODYSSEY OUTCOMES trial, among patients with recent acute coronary syndrome, who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who were treated with alirocumab then among those who received placebo. The treatment with alirocumab in patients with recent acute coronary syndrome was associated with reduction in death from any causes. The absolute risk reduction with alirocumab was the most prominent in the subpopulation of patients with low-density lipoprotein cholesterol ≥2,6 mmol/l at baseline. These results have implication for clinical practice and may play an important role for the improvement of outcomes in patients at highest cardiovascular risk after acute cardiovascular syndrome.
The possibilities of P2Y12 receptor inhibitors application in the treatment of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) are discussed in the article. The results of 4 registries in which a comparative analysis of the efficacy and safety of prasugrel with clopidogrel or ticagrelor was performed, as well as of all 3 P2Y12-receptor inhibitors among themselves, are considered in detail. The feasibility of replacing clopidogrel to prasugrel during the inpatient treatment of patients with ACS and PCI was evaluated additionally in the MULTIPRAC registry. The results of the registries demonstrate that the use of prasugrel in patients with ACS and PCI is associated with a significant reduction in the risk of ischemic complications and mortality with an acceptable risk of bleeding. At the same time, prasugrel was more effective and safer than clopidogrel and at least was non-inferior to ticagrelor, and according to some registries, even surpasses it in a number of indicators.
CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY 
Review presents data on medicines from the new group of cardiovascular drugs, direct oral anticoagulants (DOACs) inhibitors, as antidotes for DOAC when stopping life-threatening bleeding. DOAC therapy is accorded by hemorrhages with lower frequency than therapy by indirect anticoagulants, but really exist. New antidotes for DOACs are idarucizumab, andexanet, ciraparantag. The need in antidotes for DOAC may suddenly appear in spontaneous bleeding, during surgical operation, invasive procedure, due to trauma, in patients with stroke, kidney or liver failure. Data is given on the frequency of the main types of bleeding while taking new oral anticoagulants. Information concerning use of antidotes for DOACs in bleedings as well as use of non-specific therapy are reviewed.
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