PROBLEM OF TREATMENT WITH STATINS IN RUSSIA: WILL GENERICS HELP?

The article underlines necessity of statins treatment for patients with high risk of cardio-vascular events. It is noted that in our country these drugs are used extremely seldom. The problem of generic-statins equivalence to original drugs is considered

CAMELLIA TRIAL: COMPARISON IN THERAPIES BASED ON CARVEDILOL AND METOPROLOL IN HYPERTENSIVE PATIENTS WITH OVERWEIGHT AND OBESITY

Therapy of arterial hypertension in patients with overweight and obesity has peculiarities. Reasons for comparable study of efficacy and safety of therapies based on β-blockers (carvedilol and metoprolol) in this type of patients are presented. Study aims and design, efficacy and safety criteria are described

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

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

PHARMACOECONOMIC ANALYSIS OF CARVEDILOL THERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION AND METABOLIC RISK FACTORS (ACCORDING TO THE CAMELLIA STUDY)

Aim. To perform cost-effectiveness analysis of 24 weeks antihypertensive therapy based on carvedilol or metoprolol in patients with arterial hypertension (HT) 1-2 degrees and overweight/obesity. To assess effects of carvedilol therapy on 10-year expected risk of cardiovascular complications (CVC).Material and methods. Patients with HT and overweight/obesity (n=320) were included into the study and randomly split in two groups. Patients of the first group (n=160) received carvedilol as a basic therapy and patients of the second group (n=160) — metoprolol. Both groups of the patients were comparable on key clinical characteristics.Results. In 24 weeks of treatment systolic and diastolic blood pressure (BP) decreased significantly in comparison with the baseline level (p<0.0001). Dose doubling of beta-blockers was required more often in patients treated with carvedilol. At the same time a combined antihypertensive therapy of the patients treated with carvedilol was required less (p>0.05). Target BP levels were achieved in carvedilol and metoprolol groups in 96.2and 95.5% of patients respectively (p=0.85). Carvedilol had better effect on plasma metabolic indicators such as glucose (p<0.01), lipid profile, uric acid level. Reduction in expected 10-year risk of death was more pronounced in 24 weeks carvedilol treatment. Cost of target BP level achievement was approximately 2.5 times higher in carvedilol group than this in metoprolol group. However cost of additional therapy was higher in metoprolol group. 1% reduction of the 10-year expected risk of CVC death cost 1 847 rubles in carvedilol therapy.Conclusion. Carvedilol therapy (vs metoprolol one) has a higher cost under comparable efficacy. Additional expenses are compensated with the favorable effect on metabolic indices and a more pronounced effect on reduction in the 10-year expected risk of CCO death. That is why carvedilol can be recommended to patients with HT and metabolic risk factors. Longer studies are necessary to assess an effect of carvedilol therapy on prognosis in patients with HT and concomitant metabolic disorders

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

ESTIMATION OF CLINICAL AND PHARMACOKINETIC EQUIVALENCE OF ORIGINAL AND GENERIC CARVEDILOLS IN PATIENTS WITH HYPERTENSION OF 1-2 GRADES

Aim. To study clinical equivalence of original (DilatrendR, ≪Hoffmann-La Roche≫, Switzerland) and of generic (VedicardolR, ≪Synthesis≫, Russia) carvedilols with estimation of their serum level. And to study pharmacoeconomic advantages of their usage in patients with arterial hypertension (HT) of 1-2 stages.Material and methods. Study was double blind, randomized, crossed. 30 patients (8 men and 22 women, 57 y.o. average) with HT of 1 stage (3,3 %) and 2 stage (96,7 %) were included in the study. Original or generic carvedilols (12,5 mg twice a day) were prescribed to the patients. Hydrochlorothiazide was added followed carvedilol dose enlargement if initial antihypertensive effect had been insufficient. The second similar course of therapy with other carvedilol took place in 2 weeks after cancellation of the first carvedilol. Carvedilol serum level, blood pressure (BP), heart rate (HR) and side effects were registered on each visit.Results. 75 % of Vedikardol-group patients and 75 % of Dilatrend-group patients had reached target BP level (<140/90 mm Hg). Monotherapy was effective more than in a half of patients in both groups. Dilatrend had more expressed influence on HR in comparison with Vedikardol. Both drugs did not differ significantly in frequency and intensity of side effects.Conclusion. Generic carvedilol (VedicardolR) has clinical efficiency and pharmacokinetics similar to these of original carvedilol (DilatrendR). Generic carvedilol has lower cost of treatment than this in original carvedilol

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

Changes in Long-term Mortality in Patients with Myocardial Infarction History According to the LIS Luberetskiy registry

Aim. The aim of the research was to study the dynamics of distant cases of the disease that underwent AMI in 2005-2007 (LIS registry) and in 2014 and 2018 (LIS-3 registry), discharged from the same hospital of the Lyubertsy District Hospital (LDH).Material and methods. The study was conducted on the basis of two registries - a retrospective-prospective register LIS (Lyubertsy investigation of death), which was conducted in the Lyubertsy district of the Moscow region, all cases of check-ups in the AMI hospital for a 3-year period (2005- 2007) and the prospective register LIS-3 (11/01/2013 – to the present), which included patients admitted to the cardiology department of the Lyubertsy District Hospital No. 2 with the correct diagnosis of Acute coronary syndrome with and without ST segment elevation. With patients discharged from the hospital, a telephone contact was established no earlier than 1 year after discharge to clarify the life status, and in case of death – to find out its causes. Search for patients who did not answer the phone call, was using by the study of the archive of the polyclinic, with database statistics. Longterm cases of the LIS were compared with LIS-3 registers, clinical demographic characteristics and risk indicators in patients in the LIS and LIS-3 registers were also compared, differences in drug therapy before the onset of AMI and after discharge from the hospital register between LIS and LIS3 were analyzed.Results. Out of 327 patients, the registry included 104 (31.8%) patients discharged in 2014 and 223 (68.2%) in 2018. When comparing the longterm mortality curves of the LIS and LOS-3 registers, a significant difference was noted. The LIS-3 study revealed more frequent referrals for antiplatelet agents (20% vs 16%), statins (11.6% vs 2.0%). Less commonly, diuretics began to be prescribed at the prehospital level. After discharge from the hospital in the LIS-3 registry, a decrease compared to the LIS registry, more frequent prescription of antiplatelet agents (97.5% vs 85.0%), anticoagulants (1.1% vs 0%), statins (96.5% vs 67.0%), beta-blockers (93.3% vs 81.0%). Less commonly, diuretics are prescribed at discharge from the hospital.Conclusion. The present study of the LIS-3 registry showed a significant decrease in the incidence of those who had AMI, which occurred 15-20 years after the LIS registry was conducted