Сравнение особенностей медикаментозной вторичной профилактики сердечно-сосудистых заболеваний у пациентов, перенесших инфаркт миокарда, в амбулаторных условиях за 2001-2006 гг. (фармакоэпидемиологическое исследование)

The two-stage retrospective review of 1375 medical records of ambulatory patients with myocardial infarction was carried out in order to assess the delivery rate of up-to-date international and domestic guidelines for secondary CVD prevention over a period of 2001- 2006. The gap between the current guidelines for medicamental prophylaxis and their implementation in clinical outpatient practice was revealed. In spite of the fact that doctors began to prescribe preventive drugs more often target levels for cholesterol and blood pressure were not achieved in the major part of patients with myocardial infarction. The prescription rate of antiaggregants, anticoagulants and statins is still rather low.Проведен двухэтапный ретроспективный анализ амбулаторных карт 1375 пациентов кардиологического диспансера, перенесших инфаркт миокарда, на предмет выполнения международных и отечественных рекомендаций по медикаментозной вторичной профилактике ССЗ за период 2001-2006 гг. На этапе амбулаторного лечения выявлено несоответствие между существующими стандартами медикаментозной профилактики и их реализацией в клинической практике. Несмотря на то, что основные группы лекарственных препаратов стали назначаться достоверно чаще, больше чем у половины больных не были достигнуты целевые уровни показателей липидного профиля и артериального давления. В недостаточной мере продолжают применяться в амбулаторных условиях антиагреганты, антикоагулянты и статины

Five-Year dynamics of secondary prevention in patients with stable angina at specialized out-patient level in Moscow (Pharmacoepidemiology Study)

Aim. To assess five-year trend in terms of specialists' adherence to guidelines on secondary prevention of cardiovascular diseases in patients with stable angina on the level of out-patient specialized healthcare institution in Moscow. Material and methods. Two-stage retrospective pharmacoepidemiological study was conducted. The object of the study - patient medical records. At the first stage of the study medical records of 2915 patients with stable angina visited the healthcare institution for the first time in 2006 were included; at the second stage - medical records of 1633 patients with stable angina with primary visit in 2011. Results. Over the five-year period prescription rates of drugs improving prognosis in patients with stable angina significantly increased: antiplatelets - up to 82.7%, beta-blockers - up to 74.3%, statins - up to 45.6%. Despite of no changes registered in prescription rate of the ACE inhibitors, marked increase up to 14.7% in prescription rate of angiotensin receptor blockers was revealed. In the prescription structure of pharmacological groups changes were detected concerning the preferred choice of a specific drug. Due to implementation of dual antiplatelet therapy into clinical practice a reduced number of recommendations of acetylsalicylic acid as monotherapy (down to 93.0%) and increased - in combination with clopidogrel (up to 5.4%) was registered at the second stage of the study. Over a five-year period bisoprolol (55.0%) occupied the leading position in the group of beta-blockers. Metoprolol's prescription rate decreased to 27.4%. Prescription rate of atenolol decreased down to 3.1%, while that of nebivolol increased up to 8.3%. When choosing among statins specialists recommended significantly more often atorvastatin (up to 52.9%). In the group of ACE inhibitors three drugs preserved their leading positions. Meanwhile the number of recommendations of enalapril increased up to 50.8%, perindopril - up to 24.1%. Analysis of prescribed doses revealed significant increase in recommendations of specific drugs in higher daily doses: acetylsalicylic acid 100 mg - up to 71.1%, simvastatin and atorvastatin 20 mg - up to 60.5% and 41.9%, respectively. When prescribing beta-blockers and ACE inhibitors specialists continued to use minimal and medium therapeutic doses, possibly due to dose titration in patients with comorbidities. Conclusion. Study results demonstrated positive trend in terms of specialists' adherence to guidelines on secondary prevention of cardiovascular diseases in patients with stable angina. However, a number of problem aspects were identified that require further optimization of medical and preventive measures in healthcare institutions. © 2018, Stolichnaya Izdatelskaya Kompaniya

Secondary prevention in patients after myocardial infarction at ambulatory specialized cardiology institution (pharmacoepidemiology study)

Aim. To assess 5 years trend in level of doctor's adherence to actual guidelines on secondary prevention of cardiovascular diseases in patients with a history of myocardial infarction in ambulatory specialized healthcare institution in Moscow. Material and methods. There were 752 patients firstly visited healthcare institution in 2006 and 825 patients - in 2011. Their data was included in two-stage retrospective pharmacoepidemiology study. Results. Prescription rate significantly increased for three of four prophylactic groups recommended for patients with a history of myocardial infarction (antiplatelets - 91.76%, beta-blockers - 83.39%, statins - 69.45%). When assessing prescribed doses of drugs, an increase in a number of their higher doses prescriptions was revealed (at the second stage of the study acetylsalicylic acid 100 mg/day received 75.32% of patients, enalapril 20 mg/day - 30.45%, simvastatin and atorvastatin 20 mg/day - 64.52% and 47.89% of patients, respectively). Conclusion. Results showed growing level of doctor's adherence to actual recommendations on therapy and secondary prevention of cardiovascular diseases. Nevertheless, the level of adherence remains unsatisfactory and requires additional work with doctors

Проблема злоупотребления участием в клинических исследованиях ранних фаз со стороны здоровых добровольцев

This article discusses important problem of early phase clinical trials - over-volunteering. The overlapping or dual enrollment of healthy volunteers is a potential high risk not only to study subjects, but also to commercial sponsors because it could cause the delay in advancement of promising drug candidates. The problem of over-volunteering is payed special attention by clinical research professionals in foreign countries. Guidelines for early phase clinical trials recommend implementation of different control and prevention measures of multiple enrollment. The most effective instrument to prevent over-volunteering is considered to be a central internet-based registry of healthy volunteers. Such registries operate in various countries and differ in structure, scope of information collected, types of funding and management. The general operating principles of such registries are described on the example of TOPS data base. TOPS is а special system to prevent over-volunteering that is used by UK phase 1 units. In conclusion, authors urge regulatory authorities and pharmaceutical companies to approach this problem closely because over-volunteering is already a burning issue in our country. It is essential to improve relevant regulatory framework and launch central registries of healthy subjects with regard to international experience.В настоящей статье авторы затрагивают важную проблему практики клинических исследований ранних фаз - проблему злоупотребления участием в исследованиях со стороны здоровых добровольцев («профессиональное» волонтёрство). Злоупотребление участием в клинических исследованиях несёт в себе значительные риски не только для самих добровольцев, но и для разработчиков новых лекарственных препаратов, нанося последним ощутимый экономический ущерб. Данной проблеме уделяется особое внимание со стороны профессионального сообщества западных стран. В зарубежных нормативных документах, регулирующих ранние фазы клинических исследований, представлены рекомендации по внедрению различных мер контроля и профилактики «профессионального» волонтёрства. Наиболее эффективным инструментом признаны централизованные электронные регистры (базы данных) здоровых добровольцев, которые созданы на территории ряда стран Европы и Северной Америки. При этом регистры добровольцев различаются по структуре, объёму собираемой информации, типам финансирования и управления. На примере системы TOPS, которая используется центрами 1-й фазы Великобритании, описан алгоритм работы таких регистров. В заключении авторы призывают регулятора и фармацевтические компании обратить особое внимание на данную проблему, ставшую актуальной и для отечественной практики клинических исследований ранних фаз. Необходимо совершенствовать нормативную базу, регулирующую данный аспект, а также создавать централизованные регистры здоровых добровольцев с учётом международного опыта

Secondary prevention of cardiovascular diseases among patients of different age groups with a history of myocardial infarction by the example of outpatient cardiology institution

Aim. To study secondary prevention of cardiovascular diseases among patients of different age groups with a history of myocardial infarction by the example of outpatient cardiology institution. Material and methods. Retrospective pharmacoepidemiological study was conducted by analyzing the medical records of 825 patients with a history of myocardial infarction, who visited the outpatient cardiology institution for the first time in 2011. Patients were divided into two groups according to their age: younger than 60 years (n=308), and 60 years and older (n=517). Results. The population of elderly patients was more severe: significantly more often patients had disability and co-morbidities. The prevalence of the main modifiable risk factors could not be assessed fully due to the lack of information in patients' medical records. Elderly patients were significantly less likely to receive β-blockers (80.3%) and statins (63.8%). No significant differences were found in daily doses of the main prescribed preventive drugs between two groups. Conclusion. Secondary prevention of cardiovascular diseases among patients of different age groups could not be considered proper, as there is low level of attention to the modifiable risk factors and recommendation on their correction. A tendency to under-prescription of angiotensin converting enzyme inhibitors was revealed, as well as significantly lower number of recommendations for taking statins and β-adrenoblockers in the group of elderly patients

Drug interchangeability: Clinical efficacy and safety

The paper deals with the problem of the interchangeability of brand-name and generic drugs. Touching upon official terminology and the normative documents that govern the registration of generics in Russia and foreign countries, the authors state that there is no concerted approach to estimating drug interchangeability, indicate that there are some disadvantages of using a method for proving the bioequivalence of the compared drugs as evidence for their therapeutic equivalence, and point out that Russia's legal regulation of drug circulation lacks attention to the proper use of generics. The problem of interchangeability is particularly acute when prescribing narrow therapeutic range drugs, including anticonvulsant drugs. The results of the investigations discussed in the article demonstrate the need for a very cautious approach to using generic drugs in the therapy of epilepsy due to the fact that the disease may worsen. The authors come to the conclusion that treatment with less expensive generic drugs is far from always more economical. The change from a brand-name for a generic drug should be carefully approached, basing on the data of properly designed and conducted studies of therapeutic equivalence

Многофакторный анализ приверженности специалистов первичного звена современным подходам к фармакологическому лечению стабильной ишемической болезни сердца

Aim. To study predictors of primary care physician adherence to guideline-recommended pharmacotherapy of stable coronary artery disease. Material and methods. This pharmacoepidemiologic cross-sectional study was conducted in primary care setting of Moscow. 805 patients (mean age 68.9±9.9 years, males 51.4%) with established stable coronary artery disease (SCAD) were included. Demography, medical history, prescribed pharmacological treatment data were obtained. Physician adherence to guideline-recommended pharmacotherapy (GRP) of SCAD was evaluated based on the Class I guideline recommendations. Pharmacotherapeutic guideline adherence index (PGAI) was introduced as composite quality indicator, calculated in line with "all-or-none" rule and in regard with documented contraindications. To search for predictors of adherence the patient population was divided in two groups by level of physician adherence measured by PGAI. Statistical analysis was performed by IBM SPSS Statistics 16.0, the level of statistical significance was set at p<0.05. Results. The prescription rates of essential drug therapies of SCAD (regarding contraindications) were quite adequate: Beta-blockers/calcium channel blockers - 90,1%, acetylsalicylic acid/clopidogrel/oral anticoagulants - 95,7%, statins/ezetimibe - 86,3%, angiotensin-converting enzyme inhibitors/ angiotensin II receptor blockers - 87,6%. 82,9% (n=667) of patients were prescribed treatment for SCAD in compliance with the guidelines. Suboptimal pharmacotherapy was identified in 17,1% (n=138) of patients. These groups were similar in sex distribution (males 50,4 vs. 56,5%; p=0,188). Mean age tended to be lower in GRP adherent group (68,5±9,9 vs. 70,6±10,0 years; p=0,052). Bivariable analysis showed that good adherence to guideline-recommended pharmacotherapy was associated with higher prevalence of stable angina (66,4 vs. 53,6%; p=0,004), arterial hypertension (93,3 vs. 79,7%; p<0,001) and dyslipidemia (21,4 vs. 9,4%; p<0,001) and with lower prevalence of myocardial infarction (48,1 vs. 67,4%; p<0,001). Logistic multivariable regression model (gender, age, 6 medical history variables) identified 6 patient-related factors that were significantly associated with physician adherence to guideline-recommended pharmacotherapy: Age (odds ratio [OR] 0,97; 95% confidence interval [CI] 0,95-0,99; p=0,009), arterial hypertension (OR 3,89; 95%CI 2,19-6,90; p<0,001), dyslipidemia (OR 2,31; 95%CI 1,23-4,34; p=0,009), chronic heart failure (OR 1,95; 95%CI 1,06-3,61; p=0,032), revascularization (OR 2,14; 95%CI 1,33-3,45; p=0,002), myocardial infarction (OR 0,28; 95%CI 0,16-0,48; p<0,001). Conclusion. Primary care cardiologist adherence to guideline-recommended pharmacotherapy of SCAD was satisfactory evaluated as 82,9% by composite indicator PGAI. Arterial hypertension, heart failure, dyslipidemia revascularization were predictors of better physician adherence. History of myocardial infarction and older age were risk factors of non-adherence. Identification of patient-related factors associated with underperformance may facilitate tailoring quality improvement interventions in primary care of coronary patients. © 2021 Stolichnaya Izdatelskaya Kompaniya. All rights reserved.Цель. Изучить предикторы приверженности врачей первичного звена клиническим рекомендациям в области фармакотерапии стабильной ишемической болезни сердца (ИБС). Материал и методы. В амбулаторно-поликлиническом учреждении г. Москвы выполнено фармакоэпидемиологическое исследование методом поперечного среза. Включено 805 пациентов (средний возраст 68,9±9,9 лет; 51,4% мужчин) с установленным диагнозом стабильной ИБС. Регистрации подлежали данные демографии, медицинского анамнеза и фармакотерапии. Приверженность врачей оценивали на основании степени соответствия фактически назначенного медикаментозного лечения основным положениям клинических рекомендаций (класс I). Предложен фармакотерапевтический индекс соответствия клиническим рекомендациям (ФИСКР), рассчитываемый согласно подходу «все или ничего» и с учетом противопоказаний. Для анализа предикторов приверженности популяция пациентов была разделена на две группы в соответствии с оценкой по ФИСКР. Результаты. Структура назначений, обязательных для медикаментозного лечения стабильной ИБС фармакологических групп (с учетом противопоказаний), находилась на достаточно приемлемом уровне: бета-адреноблокаторы/блокаторы кальциевых каналов – 90,1%, ацетилсалициловая кислота/клопидогрел/оральные антикоагулянты – 95,7%, статины/эзетимиб – 86,3%, ингибиторы ангиотензин-превращающего фермента/антагонисты рецепторов ангиотензина II – 87,6%. Согласно оценке по ФИСКР 82,9% (n=667) пациентов получали фармакотерапию в полном соответствии с клиническими рекомендациями, 17,1% (n=138) больным фармакологическое лечение было назначено с отклонением от рекомендаций. Данные группы не отличались по гендерному распределению (мужчин 50,4 против 56,5%; p=0,188), средний возраст пациентов имел тенденцию к снижению в группе с высокой фармакотерапевтической приверженностью врачей (68,5±9,9 против 70,6±10,0 лет; p=0,052). В анамнезе больных этой же группы чаще наблюдались стабильная стенокардия (66,4 против 53,6%; p=0,004), артериальная гипертензия (93,3 против 79,7%; p<0,001) и дислипидемия (21,4 против 9,4%; p<0,001), реже – инфаркт миокарда (48,1 против 67,4%; p<0,001). По результатам многофакторного регрессионного анализа (пол, возраст, 6 анамнестических характеристик) показано, что увеличение возраста пациента на 1 год снижало шансы на высокую фармакотерапевтическую приверженность врача на 3% (p=0,009). Значимое влияние в качестве предикторов выполнения клинических рекомендаций показали: наличие у пациента артериальной гипертензии (отношение шансов [ОШ] 3,89; 95% доверительный интервал [ДИ] 2,19-6,90; p<0,001), дислипидемии (ОШ 2,31; 95%ДИ 1,23-4,34; p=0,009), хронической сердечной недостаточности (ОШ 1,95; 95%ДИ 1,06-3,61; p=0,032), реваскуляризации миокарда в анамнезе (ОШ 2,14; 95%ДИ 1,33-3,45; p=0,002), а наличие в анамнезе инфаркта миокарда снижало вероятность высокой приверженности (ОШ 0,28; 95%ДИ 0,16-0,48; p<0,001). Заключение. В условиях амбулаторной практики уровень приверженности врачей-кардиологов клиническим рекомендациям оказался удовлетворительным, составив 82,9% по оценке с помощью ФИСКР. Наличие в анамнезе больных артериальной гипертензии, сердечной недостаточности, дислипидемии и реваскуляризации повышало вероятность высокой фармакотерапевтической приверженности специалистов, а перенесенный инфаркт миокарда и более пожилой возраст снижало. Выявление предикторов неоптимальной приверженности должно способствовать более целенаправленной разработке мер по дальнейшему повышению качества фармакологического лечения стабильной ИБС в условиях первичного звена

Drug interchangeability: Clinical efficacy and safety

The paper deals with the problem of the interchangeability of brand-name and generic drugs. Touching upon official terminology and the normative documents that govern the registration of generics in Russia and foreign countries, the authors state that there is no concerted approach to estimating drug interchangeability, indicate that there are some disadvantages of using a method for proving the bioequivalence of the compared drugs as evidence for their therapeutic equivalence, and point out that Russia's legal regulation of drug circulation lacks attention to the proper use of generics. The problem of interchangeability is particularly acute when prescribing narrow therapeutic range drugs, including anticonvulsant drugs. The results of the investigations discussed in the article demonstrate the need for a very cautious approach to using generic drugs in the therapy of epilepsy due to the fact that the disease may worsen. The authors come to the conclusion that treatment with less expensive generic drugs is far from always more economical. The change from a brand-name for a generic drug should be carefully approached, basing on the data of properly designed and conducted studies of therapeutic equivalence

Проблема злоупотребления участием в клинических исследованиях ранних фаз со стороны здоровых добровольцев

This article discusses important problem of early phase clinical trials - over-volunteering. The overlapping or dual enrollment of healthy volunteers is a potential high risk not only to study subjects, but also to commercial sponsors because it could cause the delay in advancement of promising drug candidates. The problem of over-volunteering is payed special attention by clinical research professionals in foreign countries. Guidelines for early phase clinical trials recommend implementation of different control and prevention measures of multiple enrollment. The most effective instrument to prevent over-volunteering is considered to be a central internet-based registry of healthy volunteers. Such registries operate in various countries and differ in structure, scope of information collected, types of funding and management. The general operating principles of such registries are described on the example of TOPS data base. TOPS is а special system to prevent over-volunteering that is used by UK phase 1 units. In conclusion, authors urge regulatory authorities and pharmaceutical companies to approach this problem closely because over-volunteering is already a burning issue in our country. It is essential to improve relevant regulatory framework and launch central registries of healthy subjects with regard to international experience.В настоящей статье авторы затрагивают важную проблему практики клинических исследований ранних фаз - проблему злоупотребления участием в исследованиях со стороны здоровых добровольцев («профессиональное» волонтёрство). Злоупотребление участием в клинических исследованиях несёт в себе значительные риски не только для самих добровольцев, но и для разработчиков новых лекарственных препаратов, нанося последним ощутимый экономический ущерб. Данной проблеме уделяется особое внимание со стороны профессионального сообщества западных стран. В зарубежных нормативных документах, регулирующих ранние фазы клинических исследований, представлены рекомендации по внедрению различных мер контроля и профилактики «профессионального» волонтёрства. Наиболее эффективным инструментом признаны централизованные электронные регистры (базы данных) здоровых добровольцев, которые созданы на территории ряда стран Европы и Северной Америки. При этом регистры добровольцев различаются по структуре, объёму собираемой информации, типам финансирования и управления. На примере системы TOPS, которая используется центрами 1-й фазы Великобритании, описан алгоритм работы таких регистров. В заключении авторы призывают регулятора и фармацевтические компании обратить особое внимание на данную проблему, ставшую актуальной и для отечественной практики клинических исследований ранних фаз. Необходимо совершенствовать нормативную базу, регулирующую данный аспект, а также создавать централизованные регистры здоровых добровольцев с учётом международного опыта

Five-Year dynamics of secondary prevention in patients with stable angina at specialized out-patient level in Moscow (Pharmacoepidemiology Study)

Aim. To assess five-year trend in terms of specialists' adherence to guidelines on secondary prevention of cardiovascular diseases in patients with stable angina on the level of out-patient specialized healthcare institution in Moscow. Material and methods. Two-stage retrospective pharmacoepidemiological study was conducted. The object of the study - patient medical records. At the first stage of the study medical records of 2915 patients with stable angina visited the healthcare institution for the first time in 2006 were included; at the second stage - medical records of 1633 patients with stable angina with primary visit in 2011. Results. Over the five-year period prescription rates of drugs improving prognosis in patients with stable angina significantly increased: antiplatelets - up to 82.7%, beta-blockers - up to 74.3%, statins - up to 45.6%. Despite of no changes registered in prescription rate of the ACE inhibitors, marked increase up to 14.7% in prescription rate of angiotensin receptor blockers was revealed. In the prescription structure of pharmacological groups changes were detected concerning the preferred choice of a specific drug. Due to implementation of dual antiplatelet therapy into clinical practice a reduced number of recommendations of acetylsalicylic acid as monotherapy (down to 93.0%) and increased - in combination with clopidogrel (up to 5.4%) was registered at the second stage of the study. Over a five-year period bisoprolol (55.0%) occupied the leading position in the group of beta-blockers. Metoprolol's prescription rate decreased to 27.4%. Prescription rate of atenolol decreased down to 3.1%, while that of nebivolol increased up to 8.3%. When choosing among statins specialists recommended significantly more often atorvastatin (up to 52.9%). In the group of ACE inhibitors three drugs preserved their leading positions. Meanwhile the number of recommendations of enalapril increased up to 50.8%, perindopril - up to 24.1%. Analysis of prescribed doses revealed significant increase in recommendations of specific drugs in higher daily doses: acetylsalicylic acid 100 mg - up to 71.1%, simvastatin and atorvastatin 20 mg - up to 60.5% and 41.9%, respectively. When prescribing beta-blockers and ACE inhibitors specialists continued to use minimal and medium therapeutic doses, possibly due to dose titration in patients with comorbidities. Conclusion. Study results demonstrated positive trend in terms of specialists' adherence to guidelines on secondary prevention of cardiovascular diseases in patients with stable angina. However, a number of problem aspects were identified that require further optimization of medical and preventive measures in healthcare institutions. © 2018, Stolichnaya Izdatelskaya Kompaniya