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

News of the Annual Congress of the European Society of Cardiology in Munich: Research to Help Practical Medicine

The article is devoted to the discussion of the main news  from the annual congress of the European Society of Cardiology (Munich, August 25-29, 2018). The results of just completed randomized clinical trials (RCTs) are reviewed. The RCTs presented at the congress were mainly devoted not to new drugs,  but to the features of the use of already known drugs,  which was important for clinical practice

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

Efficacy, Safety and Long-term Outcomes of Nicorandil Use in Patients with Stable Ischemic Heart Disease According to the Results of Randomized and Observational Studies

Working Group of the NIKEA Study. Yekaterinburg: Akulina E.N., Reznik I.I.; Izhevsk: Grebnev S.A., Yezhov A., Shinkareva S.E.; Krasnodar: Kudryashov E.A., Skibitsky A.V., Skibitsky V.V., Fendrikova A.V.; Krasnoyarsk: Altayev V.D., Matyushin G.V., Nemik D.B., Pitaev R.R., Samokhvalov E.V., Stolbikov Yu.Yu.; Moscow: Balashov I.S., Voronina V.P., Gaisenok O.V., Dmitrieva N.A., Zagrebelny A.V., Zakharova A.V., Zelenova T.I., Kolganova E.V., Leonov A.S., Lerman O.V., Maximova M.A., Sladkova T.A., Shestakova G.N.; Novosibirsk: Kuimov A.D., Shurkevich A.A.; Omsk: Goodilin V.A., Loginova E.N., Nechaeva G.I.; Orel: Zhuravleva L.L., Lobanova G.N., Luneva M.M., Mitroshina T.N.; Orenburg: Kondratenko V.Yu., Libis R.A.; Rostov-on-Don: Dubishcheva N.F., Kalacheva N.M., Kolomatskaya O.E., Romadina G., Skarzhinskaya N.S., Chesnikova A.I., Chugunova I.B.; Ryazan: Dobrynina N.V., Nikolaev A.S., Trofimova Ya.M., Yakushin S.S.; Tula: Berberfish L.D., Gomova T.A., Gorina G.I., Dabizha V.G., Zubareva L.A., Nadezhkina K.N., Nikitina V.F., Renko I.E., Soin I.A., Yunusova K.N.Background. Nicorandil is an antianginal drug for which, the ability to positively influence the prognosis of patients (pts) with stable ischemic heart disease (IHD) was confirmed in a randomized controlled trial (RCT) of IONA (the Impact Of Nicorandil in Angina). To study whether the results of RCTs are reproduced in real clinical practice seems to be an actual scientific and practical task.Aim. To compare the data on the effectiveness and safety of nicorandil in pts with stable IHD obtained in the NIKEA observational study (OS) and in the IONA randomized study.Material and methods. 590 pts with IHD and stable angina pectoris were included in the OS NIKEA. All pts were recommended to take nicorandil in addition to the standard antiischemic therapy. 21 months after being included in the study, 524 pts received a phone call. During the telephone contact with pts or their relatives, the life status of pts was determined. According to these results of the survey data were obtained, that 15 people died and 509 pts were alive. The events included in the primary combined endpoint (PCEP) were also determined: death from all causes, new cases of acute myocardial infarction and acute cerebrovascular accident, unscheduled operations of myocardial revascularization, hospitalization for decompensation of chronic heart failure, atrial fibrillation, unstable angina, information on taking nicorandil and other drug therapy, adverse events of drug treatment have been reported. A comparative analysis of the results of the OS NIKEA and RCT IONA was carried out. The results of the IONA study were taken according to the publication in the Lancet 2002. A comparative analysis of the results of the effectiveness of nicorandil in real practice (according to the OS results) was performed with the data obtained in the RCT: the nicorandil/placebo groups in the RCT were compared with the adherent/non-adherent nicorandil groups in the OS.Results. The follow-up duration in both studies was similar and averaged 1.6±0.5 years at RCT IONA and 1.8±0.4 years at NIKEA study. The average age of pts was 67,0±8,0 years in RCT and 65.1±9.6 years in OS. In pts of OS more pronounced comorbidity was noted (cardiovascular diseases, diabetes mellitus). Drugs that favorably affect the prognosis in pts with IHD were more often prescribed to NIKEA study pts (p<0.05). In both RCTs and OS, the antianginal effectiveness of nicorandil was confirmed. According to the OS results, a reduction in the number of angina attacks and a decrease in the need for short-acting nitrates were demonstrated. The frequency of PCEP components was higher in RCT.Conclusion. Long-term outcomes according to the NIKEA observational program for various components of the PCEP turned out to be similar to the results of RCT IONA. It is demonstrated the efficacy of nicorandil in real clinical practice

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

The Questionnaire Survey Method in Medicine on the Example of Treatment Adherence Scales

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

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

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

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