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

THE STUDY OF ANAMNESTIC FACTORS AND THEIR ROLE IN ESTIMATION OF SHORT-TERM (IN-HOSPITAL) PROGNOSIS IN PATIENTS UNDERWENT BRAIN STROKE OR TRANSIENT ISCHEMIC ATTACK, BY THE DATA FROM LIS-2 REGISTRY

Aim. To assess the role of anamnestic factors in estimation of the shortest-term (in-hospital) prognosis in patients after stroke. Material and methods. We included all patients during the period 01.01.2009 to 31.12.2011 (n=960), who were diagnosed the stroke ot TIA inMHILyubertsyDistrictHospital№2.Results. Into the registry LIS-2 included 960 patients. During hospitalization 207 patients died, in-hospital mortality was 21,6%. Mortality increased with the age, and the age became an independent death risk factor in hospital (p=0,037). Hemoorhagic stroke increased the risk of death 6,95 times, and consciousness disorders — 2-5 times (depending on the level of disorder), CHF signs— by 3,14 times, and AF— 1,86 times. These values were evaluated as independent anamnestic risk factors of the in-hospital death.Conclusion. The data from LIS-2 registry demonstrates analogy with the data from other stroke registries in RF. In-hospital mortality in LIS-2 was 2-3 times higher comparing to the registries of other countries. Factors influenced in-hospital mortality were age, type of the stroke, level of consciousness at admission, CHF and cardiac rhythm disorders as AF

The Study of Adherence to Drug Therapy at the Stage of Outpatient Follow-up in Patients with Acute Myocardial Infarction (Data from the PROFIL-IM Registry)

Aim. To assess adherence  to the recommended therapy at the stage of outpatient follow-up and its impact on long-term outcomes  in patients after acute myocardial  infarction based on the materials of the prospective PROFILE-IM registry.Material and methods. The PROFILE-IM register included 160 patients who applied to one of the polyclinics in Moscow after a myocardial  infarction. The combined endpoint (CE) included death from any cause, cardiovascular events (nonfatal myocardial infarction,  nonfatal cerebral stroke), emergency hospitalizations for cardiovascular diseases, significant  cardiac arrhythmias. Patients' adherence to therapy was assessed using the original questionnaire "Scale of Adherence of the National Society of Evidence-based Pharmacotherapy" (NODF) and a direct standardized patient survey by a doctor about taking medications. Visits to the doctor were carried out every two months,  data from the first year of patient follow-up are presented.Results. In a personal  interview  with a doctor,  the ratio of the proportion  of committed, partially  committed  and non-committed patients  did not change  significantly over the entire follow-up period, while the proportion of committed patients was 81-85%. The "NODF Adherence Scale" showed that the proportion of non-committed patients was about 10 times higher than with direct patient responses to the doctor, and the proportion of non-committed  and partially committed  patients remained high at all stages of follow-up (respectively 28% and 10% at the beginning of the study, 18% and 10% at the end of the study).  Among the main factors  of non-commitment, there was a decrease  in the importance  of forgetfulness and an increase  in factors  such  as fear  of side effects  of medications, doubt  about  the need  for long-term use of medications  and  well-being. A  direct relationship of adherence with the male sex, the presence of hypertension, a feedback  relationship with alcohol consumption was revealed. The risk of CE in non-committed patients was higher compared  to the group of committed  and partially committed  patients (p<0.01).Conclusion. The proportion of non-committed and partially committed patients remained high at all stages of follow-up. There was a direct relationship between adherence to therapy with the male sex, the presence of hypertension in the anamnesis, and a feedback relationship with alcohol consumption. Low adherence to therapy significantly increased the risk of cardiovascular events

INFLUENCE OF PATIENTS’ PREHOSPITAL ATTENDANCE AT OUTPATIENT CLINICS ON LONG-TERM OUTCOMES OF ACUTE CORONARY SYNDROME: LIS-3 STUDY

Aim. To assess influence of patients’ prehospital attendance at outpatient clinics on long-term outcomes of acute coronary syndrome (ACS).Material and methods. Patients (n=397) hospitalized with ACS (01.11.2013-31.07.2015) were included. 19.4% of patients died in hospital (77/397).-According to their rate of attendance at outpatient clinics all survived patients (n=320) were divided into 3 groups: committed to visiting outpatient-clinics (n=139), partially committed (n=103) and not committed (n=78). Follow-up period was 14-35 months (88.44% follow-up rate). During-follow-up period 12.5% of patients died (40/320). All-cause mortality and recurrent cardiovascular diseases (nonfatal myocardial infarction and stroke,-unstable angina) were defined as the primary endpoint. Prognostic significance of separate factors and their combinations were assessed by their influence on the primary endpoint.Results. Clinical severity of course of the disease was assessed regarding all factors that had influence on the primary endpoint. By their degree of influence on the primary endpoint each factor was given a certain score. According to the sum of all scores patients were divided into 2 groups: patients with less (n=205) and more (n=78) severe clinical course of the disease. Risk of development of primary endpoint was higher in patients with more severe clinical course of the disease (relative risk 3.997; 95% confidence interval 2.199-7.267; p <0.0001) regardless of patients’ attendance at outpatient-clinics (p>0.05).Conclusion. Patients’ prehospital attendance at outpatient clinics did not affect long-term outcomes of acute coronary syndrome. Patients with more-severe clinical course of the disease were more likely to develop adverse outcomes during the follow-up regardless of their prehospital attendance at outpatient clinics

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

Adherence to Visits to Medical Institutions and Quality of Therapy after Acute Coronary Syndrome (according to the LIS Registry 3)

Aim. The aim of the research is to evaluate the relationship between patients' adherence to visiting polyclinics after acute coronary syndrome (ACS) and the quality of the therapy they receive.Material and methods. The study was conducted on the basis of the LIS registers (LIS and LIS-3) (Lyubertsy study of mortality) in the Lyubertsy district of the Moscow region. To clarify the vital status of all patients discharged in the first 9 months of 2014 and 2018. from Lyubertsy district hospital 2, contact was established no earlier than 1 year after discharge, and in case of death, its cause was clarified. In the course of a telephone survey, information was obtained on the therapy taken, adherence to visits to medical institutions, a record of cases of cardiovascular events and invasive treatment, hospitalizations due to worsening of the course of the underlying disease for the period after discharge from the hospital was carried out. The search for patients who did not answer the phone call was carried out by studying the archives of polyclinics, using the Megaclinic statistical database, and the data of the individual rehabilitation program for the disabled. In the course of a telephone survey, the response was 60.5%, the search for the remaining patients through statistical databases, the archive of polyclinics made it possible to increase the total response to 87.2%.Results. In the LIS-3 registry, out of 104 patients discharged in 2014, the status was determined in 90 (86.5%) patients, out of 223 patients in 2018 – in 195 (87.4%) patients. During the survey, it was found that 172 patients are observed after discharge from the hospital, 53 patients are not observed at all in the medical facility after discharge. 11 (4.9%) people did not take any groups of medications at the time of the survey. In the group of patients who are highly committed to attending a health facility, the best quality of taking essential medications after discharge from the hospital was noted according to the survey: statins (88.2%, p<0.001), beta-blockers (86.4%, p<0.001) and antiplatelets (90.9%, p=0.001). In both groups, committed and not committed to attending a medical facility, there is a negative dynamics in the quality of taking medications after discharge from the hospital, however, in the group of patients committed to attending a medical facility, it was noted that the odds of taking antiplatelet agents after discharge was 3.4 times higher (OR 3.449, p=0.002), beta-blockers – 4 times (OR 4.103, p<0.001), statins – 4.5 times (OR 4.450, p<0.001), in relation to the group of patients who are not observed in the medical facility after discharge from the hospital.Conclusion. 1-6 years after discharge from the hospital after the reference event, the quality of therapy deteriorated significantly in both groups, mostly in non-adherent patients. Significant differences in the quality of medication intake (antiplatelet agents, statins, β-blockers) were noted in the group of adherents to visiting health care facilities in comparison with those who were not committed to visiting health facilities. It is obvious that high adherence to visits to healthcare facilities after discharge from the hospital is associated with better quality of medication intake. Despite improvements in the quality of adherence to clinical recommendations, the percentage of patients who independently refuse to take drug therapy (4.9%), regardless of visits to healthcare facilities after discharge from the hospital, remains