The Safety of Nicorandil Therapy and the Relationship with Treatment Adherence in Patients with Stable Angina Pectoris (According to the NIKEA Observational Study)

The working group of the NIKEA study: Reznik I.I. (Ekaterinburg), Akulina E.N. (Ekaterinburg), Ezhov A.V. (Izhevsk), Shinkareva S.I. (Izhevsk), Grebnev S.A. (Izhevsk), Skibitsky V.V. (Krasnodar), Kudryashov E.A. (Krasnodar), Fendrikova A.V. (Krasnodar), Skibitsky A.V. (Krasnodar), Matyushin G.V. (Krasnoyarsk), Nemik D.B. (Krasnoyarsk), Pitaev R.R. (Krasnoyarsk), Altaev V.D. (Krasnoyarsk), Samokhvalov E.V. (Krasnoyarsk), Stolbikov Y.Y.. (Krasnoyarsk), Voronina V.P. (Moscow), Lerman O.V. (Moscow), Gaisenok O.V. (Moscow), Dmitrieva N.A. (Moscow), Zagrebelny A.V. (Moscow), Zakharova A.V. (Moscow), Balashov I.S. (Moscow), Leonov A.S. (Moscow), Sladkova T.A. (Moscow), Zelenova T.I. (Moscow), Shestakova G.N. (Moscow), Kolganova E.V. (Moscow), Maksimova M.A. (Moscow), Kuimov A.D. (Novosibirsk), Moskalenko I.V. (Novosibirsk), Shurkevich A.A. (Novosibirsk), Nechaeva G.I. (Omsk), Loginova E.N. (Omsk), Gudilin V.A. (Omsk), Mitroshina T.N. (Orel), Zhuravleva L.L. (Orel), Lobanova G.N. (Orel), Luneva M.M. (Orel), Libis R.A. (Orenburg), Kondratenko V.Yu. (Orenburg), Chesnikova A.I. (Rostov-on-Don), Kalacheva N.M. (Rostov-on-Don), Kolomatskaya O.O. (Rostov-on-Don), Dubishcheva N.F. (Rostov-on-Don), Romadina G.V. (Rostov-on-Don), Chugunova I.B. (Rostov-on-Don), Skarzhinskaya N.S. (Rostov-on-Don), Dobrynina N.V. (Ryazan), Yakushin S.S. (Ryazan), Bulanov A.V. (Ryazan), Trofimova Ya.M. (Ryazan), Nikolaeva A.S. (Ryazan), Sokolova L.A. (St. Petersburg), Savinova E.B. (St. Petersburg), Ievskaya E.V. (St. Petersburg), Vasilyeva L.B. (St. Petersburg), Gomova T.A. (Tula), Zubareva L.A. (Tula), Berberfish L.D. (Tula), Gorina G.I. (Tula), Nadezhkina K.N. (Tula), Yunusova K.N. (Tula), Nikitina V.F. (Tula), Dabizha V.G. (Tula), Renko I.E. (Tula), Soin I.A. (Tula)Aim. To analyze the adverse events (AEs) of nicorandil therapy based on the results of an observational study of NIKEA, to assess the relationship between the occurrence of AEs treatment and adherence to it in patients with stable angina pectoris.Material and methods. The study included 590 people who had nicorandil added to the basic therapy of coronary artery disease (CAD). The followup period averaged 21 months. There were two visits of 1 and 3 months of follow-up (V1 and V3), and after 21 months, by telephone contact (PhC21), it was possible to obtain information about 524 patients (89% response), 509 of whom were alive. Information about the treatment adherence and AEs of nicorandil was collected during V1, V3 and at PhC21.Results. Out of 590 people, 402 (68.1%) patients started treatment with nicorandil. During 21 months of follow-up, 35 AEs were registered in 34 patients. There were no serious AEs associated with taking medications in the study. The most frequent AEs of treatment with nicorandil were hypotension and headache, which led to non-adherence to therapy in 94% and 42% of cases, respectively. The majority of AEs (24 out of 35) occurred during the first three months of nicorandil treatment. Both any AEs of drug therapy and AEs of nicorandil therapy, on average, increase the chance of non-adherence to the recommended treatment by 3 times (p=0.004).Conclusion. The results of the NIKEA study confirmed the good safety of nicorandil in patients with stable angina pectoris, the absence of serious adverse events associated with taking this antianginal drug. The most frequent nicorandil AEs were hypotension and headache. Any AEs of therapy increase the chance of patients' non-adherence by 3 times

Prognostic value of calcific aortic stenosis in patients of the PROGNOZ IBS registry

Aim. To assess the impact of calcific aortic stenosis on long-term prognosis in patients with stable coronary artery disease (CAD) included in the PROGNOZ IBS registry.Material and methods. The analysis included data of patients (n=541; men, 432; women, 109) from the CHD PROGNOSIS registry, in whom diagnosis of CAD was confirmed using coronary angiography during reference hospitalization in the National Medical Research Center for the period from January 1, to December 31, 2007. The mean age of men was 57,5±0,4, women — 60,9±0,9 years. The survival analysis included 504 patients (93%). The mean follow-up period was 7,3±2,19 years. We assessed the presence of calcific aortic stenosis (CAS) according to echocardiography and data on endpoints after 4 and 7 years of follow-up.Results. CAS according to echocardiography during reference hospitalization was found in 29 patients (5,4%) with a confirmed CAD. After four-year followup, 7 patients (24,1%) died, after 7 years — 15 (51,7%). Fatal and non-fatal cardiovascular events (primary endpoint) after 4 years were revealed in 10 patients (34,5%), and after 7 years, all cardiovascular events were fatal (n=15; 51,7%). In the presence of aortic stenosis, the relative risk (RR) of all-cause death at 4-year follow-up increased by 2,9 times (p<0,01), while at 7-year follow-up — by 3,2 (p<0,0001). The RR for the primary endpoint at 4-year follow-up increased by 2,8 times (p<0,01), while at 7-year follow-up — by 2,3 times (p<0,001). The RR of death in CAS patients at 7-year follow-up was comparable to severe heart failure — 3,3 (p<0,01), stroke — 2,4 (p<0,05) and left main coronary artery stenosis — 2,5 (p<0,0001).Conclusion. The presence of calcific aortic stenosis had a pronounced negative effect on the long-term prognosis of CAD patients, comparable with those in left main coronary artery stenosis, severe heart failure and stroke

COMPARATIVE ANALYSIS OF ARTERIAL HYPERTENSION TREATMENT IN MEN AND WOMEN BASED ON THE RESULTS OF ACCORD STUDY (ACRIDILOLE IN COMBINATION THERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION AND OBESITY OR TYPE 2 DIABETES)

Aim. To compare the efficacy and safety of carvedilol in men and women with mild to moderate arterial hypertension, associated with obesity and/or compensated diabetes type 2. Material and methods. Hypertensive patients (n=592, 176 men and 416 women) with obesity and/or diabetes were involved into randomized comparative open-label study in parallel groups. Patients were randomized into two groups. Patients of group A (n=291: 90 men and 201 women) kept on to receive previous antihypertensive drugs except beta-blockers which were withdrawn and replaced with carvedilol (Acridilole®, PLC “Akrikhin”, Russia). Patients of control group (n=301: 86 men and 215 women) kept on to receive only previous antihypertensive drugs. Efficacy of antihypertensive therapy was assessed at every 2-week visits during 24-week observation. Biochemical parameters of glucose and lipid metabolism, 12-lead ECG were evaluated at baseline and at the end of the study. Target blood pressure (BP) achievement and safety was assessed in 24 weeks of treatment. Results. Women had more severe metabolic abnormalities compared with men. By the 24th week of treatment significant reduction in systolic BP , diastolic BP , and heart rate was found in the both groups of patients regardless of gender , intergroup differences were significant (p<0,05). By the end of the study target BP level was achieved in 96.3% of men and 96,8% of women in group A and 85.9% and 88.8%, respectively , in the control group (p<0,001). The number of hospital admissions decreased in 4.8 times in men (p<0.0001) and 12 times - in women (p<0.05) in group A, and in 2.7 and 3.3 times, respectively , — in the control group (p<0.0001). Mild to moderate side effects were observed in 32 patients: 19 and 13 patients in group A and control group, respectively (p=0.58). Adverse event rate was not distinguished significantly between men and women. Conclusion: The results show comparable high efficacy and safety of carvedilol in hypertensive men and women with concomitant diseases and high metabolic and cardiovascular risk

Assessment of the Quality of Drug Therapy in Patients with Stable Coronary Artery Disease in the Second Stage of the ALIGN Study

Aim. To assess adjusted pharmacotherapy for prescribing drugs of the main classes, according to clinical guidelines, and achieving target levels of lowdensity lipoprotein cholesterol (LDL-C) in patients with stable coronary heart disease (CHD).Material and methods. Of the 73 patients included in the ALIGN study, 64 patients (53 males and 11 females; mean age 68,2±9,4 years) with stable coronary artery disease attended a second visit (3 months after the initial treatment adjustment). Prescribed drug therapy, its compliance with clinical guidelines, achievement of lipid profile and blood pressure (BP) targets were studied in all patients.Results. An increase in the frequency of taking beta-blockers (p=0.002), lipid-lowering drugs (p=0.008) by patients was found during the second visit. The proportion of patients taking all 4 groups of drugs according to clinical guidelines (statins, antiplatelet agents, beta-blockers, angiotensinconverting enzyme inhibitors / angiotensin II receptor blockers) increased from 44% to 65.5% (p<0.001) after correction of therapy, as well as an increase in the proportion of patients taking 1 antianginal drug in the presence of exertional angina from 75% to 89% (p<0.001) was found. About 90% of hypertensive patients achieved the target level of systolic blood pressure (p<0.001). Achievement of the target level of cholesterol low density lipoprotein (<1.8 mmol/l) during the second visit was found in half of the patients (p=0.004).Conclusion. Despite the initial correction of drug therapy by the staff of the cardiology department, the prescribed treatment for patients with stable coronary artery disease did not in all cases comply with clinical guidelines due to insufficient adherence of doctors and insufficient adherence of patients to prescribed medical recommendations.Working group of the register PROFILE: Voronina V. P., Dmitrieva N. A., Komkova N. A., Zagrebelny A.V., Kutishenko N.P., Lerman O.V., Lukina Yu. V., Tolpygina S.N., Martsevich S.Yu

The problem of obesity «through the eyes» of patients (results of the survey of patients of the outpatient registry)

Aim. To assess, based on the results of the questionnaire, patients' awareness of the presence, possible causes and health effects of overweight /obesity; to determine patients' self-assessment of their own weight, information about the methods used to treat the disease, adherence to therapy.Material and methods. The survey of patients of the outpatient registry was carried out as part of a face-to-face visit of inclusion in the observational study of EVA using a specially designed questionnaire. Out of 582 patients of the PROFILE registry who came for a visit in the period from 08.04.2019 to 24.03.2020, 295 people with a body mass index (BMI) were included in the study>25 kg/m2.Results. According to the BMI values, the patients of the study cohort were divided into 4 groups: 108 (36.6%) with pre-obesity, 124 (42.1%) with class I obesity, 42 (14.2%) with class II obesity, 21 (7.1%) with class III obesity. With an increase in the class of obesity, the number of patients who admit the presence of this pathology in self-assessment increases (p<0.0001): 26.6% of patients with grade I obesity, 47.6% with grade II obesity and 81% of patients with grade III obesity gave correct answers. Among the possible causes of overweight/obesity, every third patient of the study indicated physical inactivity (31.3%) and every fifth specified excessive nutrition (20.8%). The majority of patients, 244 (82.7%), believe that being overweight worsens their health, the same number of patients, 255 (86.4%), are sure that they need to lose weight. The most common (70% of responses) for weight loss patients used various dietary restrictions, fasting, only 17% of patients increased the level of physical activity. Frequent violation of the principles of rational nutrition was revealed (insufficient amount of fruits and vegetables in the diet, salting food, eating a large amount of easily digestible carbohydrates. One hundred and thirty nine (47.1%) patients noted that it was difficult for them to observe any restrictions in food, to adhere to a diethalf of all patients and 70% of patients with class III obesity experience a constant feeling of hunger. Of the 25 patients to whom pharmacotherapy was recommended, 21 (84%) people were adherent.Conclusion. Overweight and obese patients are not always critical of self-assessment of their body weight, and the main reasons for being overweight or obese considered to be inactivity and various violations of the principles of rational nutrition. The patients of the study cohort were characterized by eating disorders and half of the patients showed signs of food addiction. Recommendations for the pharmacotherapy of obesity were received by less than 10% of patients in the study cohort, while the patients' adherence to drug therapy was high

IMPACT OF ATRIAL FIBRILLATION ON THE NEAR AND LONG-TERM PROGNOSIS OF LIFE AFTER ACUTE MYOCARDIAL INFARCTION. THE DATA OF THE LIS-1 STUDY (LYUBERTSY MORTALITY STUDY OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION)

Aim. To study the effect of atrial fibrillation (AF) that existed before the myocardial infarction (MI), on near and long-term mortality in patients with acute MI.Material and methods. The data of LIS register (Lyubertsy study on mortality rate in patients after MI), that included all patients hospitalized for acute MI (n=1133) during the period from 1 January 2005 to 31 December 2007, were used to solve the aim of the study.Results. AF was recorded in 88 patients (7.8%), and the frequency of AF significantly increased with age. 22 patients with a history of AF (25%) died in hospital, and mortality in this group of patients was significantly higher than this in the whole group of patients (15.2%; p=0.025). However, these differences were not statistically significant when adjusted for age and gender (OR=1.25; 95% CI 0.77-2.04; p=0.37). 66 people from 961 patients, who were discharged from the hospital, had the AF before acute MI. Relative risk of death in patients with AF in this group (adjusted for age and sex) was significantly higher than this in patients without AF (OR=1.91; 95% CI 1.18-3.11; p=0.005). Conclusion. AF diagnosed in patients with acute MI at admission did not influence significantly hospital mortality. However, pre-existing AF increases significantly the risk of death in patients survived acute period of MI

Study of the Quality of Medical Therapy and Adherence in Patients with Chronic Heart Failure (According to the COMPLIANCE Study)

Aim. Assess the medical therapy quality in patients with chronic heart failure (CHF) and patients' adherence to the treatment depending on the previous observation in a specialized medical center as part of an of an outpatient registry.Materials and methods. An analysis of the medical therapy quality in patients with CHF was carried out as part of the COMPLIANCE prospective observational study (NCT04262583). 72 patients with CHF verified according to the protocol were included in the study. The average age of the patients was 69.1±9.5 years (31% of women and 69% of men). Patients were divided into groups: those who first applied to a specialized department during the period of the study inclusion, or those who were previously observed in a specialized department. The general adherence assessment to medical therapy was carried out using the original questionnaire «The adherence scale of the National Society for Evidence-Based Pharmacotherapy» which was supplemented with questions to assess the actual adherence to specific medical drugs recommended for patients with CHF.Results. According to the results of the study, beta-blockers were prescribed to 70 (97.2%) patients. Angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARBs) were recommended in 68 (94%) patients. Mineralocorticoid receptor antagonists were included in therapy in 6 out of 9 patients who were shown to be prescribed (66.6%). The choice of medical drugs within the group was not always adequate. For example, ACEi/ARBs with proven efficacy in patients with CHF were prescribed only in 72% of patients. Comparative analysis of adherence to medical therapy between patients of the selected groups demonstrated a higher adherence to the recommended therapy in patients who were previously observed in a specialized center.Conclusion. The medical therapy quality for patients with CHF doesn't always comply with current clinical guidelines. The choice of a medical drug within a group is not always adequate. Regular observation in a specialized center contributes to a higher adherence to the recommended therapy

Secondary Prevention and Quality of Life of Patients with Stable Coronary Heart Disease

Aim. To assess the quality of life of patients with stable coronary heart disease (CHD) initially and 12 months after drug and non-drug secondary prophylaxis according to clinical guidelines.Material and methods. 73 patients (57 men, 16 women) with confirmed stable coronary artery disease were included in the study, of which 44 patients described a clinic for angina pectoris of functional class I-IV. The study included 2 patient visits: an initial treatment visit (V0) and a repeat visit after 12 months (V2). At both visits, blood pressure (BP), low-density lipoprotein cholesterol (LDL-c), quality of life (QL) were assessed using SAQ (Seattle Angina Questionnaire), drug therapy. Compliance with 5 basic principles of prevention was also assessed, which included: (1) healthy lifestyle (healthy lifestyle) (rejection of bad habits (smoking), moderate physical activity, lowcholesterol and low-carb diet); (2) normalization of body weight; (3) optimal drug therapy (the frequency of taking medications was evaluated using the original questionnaire); (4) achievement of target values of LDL-c in the entire group; (5) blood pressure in hypertensive patients. During V0, if necessary, drug therapy was adjusted in accordance with clinical recommendations. During V2, 57 patients (47 men and 10 women) were examined. The response was 80.8%.Results. After 12 months of follow-up, a statistically significant improvement in exercise tolerance (p=0.003), angina stability index (p=0.045) and the frequency of stress angina attacks (p=0.003) was noted when assessing the median of QL indicators. After 12 months of follow-up, 59% of patients used optimal drug therapy, including 4 drugs according to clinical guidelines. A healthy lifestyle (regular physical activity and smoking cessation) was achieved in 20.4% after 12 months of follow-up, the target level of LDL-c ˂ 1.8 mmol/L was achieved in 44.5% of patients, and the target blood pressure was achieved in 74,6%. The achievement of all 5 principles of secondary prevention of coronary heart disease according to the results of the work carried out by the visit after 12 months of follow-up was revealed only in 7% of patients (4 patients), and the implementation of 4 principles of prevention was noted in a quarter of patients from the group (24.5%, n=14).Conclusions. With drug and non-drug secondary prevention of coronary heart disease in patients with stable CHD after a year of follow-up, a statistically significant increase in QL indicators was noted due to increased exercise tolerance and a decrease in the frequency of angina attacks. Nevertheless, the basic principles of prevention were fully implemented only in 7% of patients