Clinical Efficacy and Safety of Empagliflozin in Patients with Acute Heart Failure from the First Day of Hospitalization

Aim. Evaluation of the safety, clinical and hemodynamic effects of empagliflozin in patients with acute decompensated heart failure (ADHF) from the first day of hospitalization in the absence of signs of hemodynamic instability.Material and methods. A prospective, comparative, randomized study included 46 patients admitted to the hospital in connection with ADHF in the absence of signs of hemodynamic instability. Inclusion in the study and randomization to receive empagliflozin was carried out in the first 24 hours from the moment of admission to the hospital. The main group (n=23) from the first day of hospitalization and the entire subsequent follow-up period took empagliflozin at a daily dose of 10 and 25 mg (for patients with type 2 diabetes mellitus) in addition to basic therapy, the control group (n=23) received standard therapy without gliflozines. The observation period was 3 months and included 3 control points: 1st day of hospitalization, 7th-12th day, 3rd month of observation. Clinical, anamnestic and instrumental data were evaluated at all control points.Results. In the hospital period, by the 7th-12th day, only in the main group there was an improvement in all clinical indicators (p<0.01), an increase in the rate of diuresis (p><0.01), a decrease in the daily dose of the parenteral diuretic furosemide from 54 mg to 26 mg (p><0.01). A decrease in systolic blood pressure (SBP) occurred in both groups (p><0.01), but it was more pronounced in the comparison group [from 141 (110; 160) to 110 (90; 120) mm Hg) compared to the main group [from 140 (120; 160) to 120 (110; 130) mm Hg]. According to echocardiography data in the main group, there was a decrease in the indexed volume of the right atrium, the end-systolic volume of the left ventricle (LV ESV) and systolic pressure in the pulmonary artery, an increase in the LV ejection fraction (LV EF) (p><0.05). In the comparison group, only an increase in LV ESV was noted (p=0.04). The index of the indexed volume of the left atrium did not show significant dynamics in the main group (p=0.79), but showed a significant decrease>˂0.01), a decrease in the daily dose of the parenteral diuretic furosemide from 54 mg to 26 mg (p<0.01). A decrease in systolic blood pressure (SBP) occurred in both groups (p>˂0.01), but it was more pronounced in the comparison group [from 141 (110; 160) to 110 (90; 120) mm Hg) compared to the main group [from 140 (120; 160) to 120 (110; 130) mm Hg]. According to echocardiography data in the main group, there was a decrease in the indexed volume of the right atrium, the end-systolic volume of the left ventricle (LV ESV) and systolic pressure in the pulmonary artery, an increase in the LV ejection fraction (LV EF) (p˂0.05). In the comparison group, only an increase in LV ESV was noted (p=0.04). The index of the indexed volume of the left atrium did not show significant dynamics in the main group (p=0.79), but showed a significant decrease in the 2nd and 3rd control points compared to the control group (p=0.01 and p=0.02). Complications, against the background of taking empagliflozin, were not noted: there were no episodes of hypotension (SBP˂90 mm Hg), hypoglycemia, acute kidney injury.Conclusion. The results obtained indicate the safety of empagliflozin in patients with ADHF, regardless of the status of carbohydrate metabolism and LV EF, as well as taking into account the clinical (more intense positive dynamics of clinical symptoms of ADHF) and hemodynamic (smooth decrease in SBP, increased diuretic effect) effects of empagliflozin, this drug should be considered as an effective and safe supplement to the main therapy from the first day of hospitalization in patients with stable hemodynamic parameters

ИНФАРКТ МИОКАРДА ВТОРОГО ТИПА: СОВРЕМЕННЫЕ ОСОБЕННОСТИ ДИАГНОСТИКИ И ЛЕЧЕНИЯ

Aim. To determine the frequency of detection of patients with myocardial infarction (MI) type 2 and their features in real clinical practice.Methods. A prospective study of 204 patients diagnosed with acute coronary syndrome (ACS) was performed. Diagnosis of ACS at admission followed by a confirmed diagnosis of MI during the hospital period according to the Fourth Universal Definition of MI. The following were analyzed: anthropometric parameters, clinical and anamnestic characteristics of patients, results of laboratory research methods, determination of biochemical markers of myocardial necrosis, results of instrumental diagnostic methods and coronary angiography. The annual follow-up stage was carried out in the form of a telephone survey of patients with a follow-up of dynamic features during the year after ACS (presence of endpoints: repeated coronary events, death, repeated hospitalizations, adherence to medical recommendations, therapy taken by the patient).Results. Type 2 MI was diagnosed in 22 (10.8%) cases. The results of coronary angiography demonstrated the absence of coronary artery (CA) in 16 (72.7%) patients of this group or the presence of stenoses of less than 50% without indications of the presence of thrombosis. Chronic occlusion of the infarct-unrelated coronary artery was found in 6 (27.3%) patients. Patients with type 2 MI were comparable in age with the group of patients with type 1 MI. Differences were female predominance (p = 0.029), fewer smokers (p = 0.037) and more frequent history of atrial fibrillation (AF) (p = 0.003). The most frequent provoking factors of type 2 MI were determined: sinus tachycardia in 3 (13.6%) patients, flutter paroxysm or AF with tachysystole for the ventricles in 4 cases (18.2%).Conclusion. A less favorable course of the disease was found in patients with type 1 MI. A feature of the post-infarction period in this case was the greatest number of recurrent MI and deaths during the year compared with patients after type 2 MI, which were characterized by a predominance of women, a smaller number of smokers and people with dyslipidemia, as well as a more frequent indication of the presence of AF.Основные положенияВыявлены особенности отдаленного постинфарктного периода у больных инфарктом миокарда 2-го типа в виде благоприятного течения при сравнении с больными ИМ 1-го типа. Определены различия клинико-анамнестических данных пациентов с ИМ 1-го и 2-го типа. Аннотация:Цель. Определить частоту выявления пациентов с инфарктом миокарда (ИМ) 2-го типа и их особенностей в реальной клинической практике.Материалы и методы. Проведено проспективное исследование 204 пациентов с диагнозом «острый коронарный синдром (ОКС)». В исследование вошли лица с установленным при поступлении ОКС и последующим диагнозом ИМ, подтвержденным в госпитальном периоде согласно Четвертому универсальному определению ИМ. Проанализированы антропометрические показатели, клинико-анамнестические характеристики пациентов, результаты лабораторных методов исследования, биохимические маркеры некроза миокарда, результаты инструментальных методов диагностики и коронароангиографии. Годовой этап наблюдения осуществлялся в виде телефонного опроса пациентов с целью отслеживания динамических особенностей в течение года после перенесенного ОКС (наличия конечных точек: повторных коронарных событий, летального исхода, повторных госпитализаций по причине кардиальных и внекардиальных событий; приверженности врачебным рекомендациям и принимаемой терапии).Результаты. Диагноз ИМ 2-го типа установлен в 22 (10,8%) случаях. Результаты коронарографии продемонстрировали отсутствие поражения коронарных артерий у 16 (72,7%) больных этой группы или наличие стенозов менее 50% без указаний на тромбоз. Хроническая окклюзия инфаркт-несвязанной коронарной артерии обнаружена у 6 (27,3%) пациентов. Пациенты с ИМ 2-го типа оказались сопоставимы по возрасту с группой больных ИМ 1-го типа. Отличия заключались в преобладании лиц женского пола (p = 0,029), меньшем количестве курящих пациентов (p = 0,037) и более частом указании на наличие фибрилляции предсердий в анамнезе (p = 0,003). Определены факторы, наиболее часто провоцирующие ИМ 2-го типа: синусовая тахикардия – у 3 (13,6%) пациентов, пароксизм трепетания или фибрилляции предсердий с тахисистолией желудочков – в 4 (18,2%) случаях.Заключение. Выявлено менее благоприятное течение заболевания у пациентов, перенесших ИМ 1-го типа. Особенностью постинфарктного периода в данном случае стало наибольшее количество повторных ИМ и летальных исходов в течение года по сравнению с пациентами после ИМ 2-го типа, которые характеризовались преобладанием женщин, меньшим количеством курящих и лиц, имеющих дислипидемию, а также более частым указанием на наличие фибрилляции предсердий

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Gender-specific features of psychosocial status and their clinical effects in myocardial infarction patients

Aim. To identify gender-specific psychosocial factors, important in myocardial infarction (MI) patients, and prove the need for gender-specific approach in MI patients rehabilitation. Material and methods. The authors examined 120 women and 100 men with MI. Clinical status was assessed traditionally, psychosocial status and emotional status – with Zung depression scale, adapted by T.I. Balashova, personal and reactive anxiety scale by Spielberger and Khanin, Jenkins questionnaire on coronary behavior type,quality of life (QoL) assessment scale by Russian National Cardiology Center, Russian Academy of Medical Science. Results. In male and female MI patients, substantial psychological abnormalities were identified, proving the need for specific intervention and possible longer in-patient treatment, or combined cardiological and psychological rehabilitation, together with risk factor modification for secondary prevention of coronary heart disease. Conclusion. In development of MI rehabilitation programs, psychosocial and gender aspects should be taken into account

Participation of the C-terminal propeptide procollagen type I in the formation of cardiofibrosis in patients with myocardial infarction with preserved left ventricular ejection fraction

Aim. To study the dynamics of procollagen type I carboxy-terminal propeptide (PICP) with an assessment of potential associations with cardiac fibrosis (CF) and diastolic dysfunction (DD) of the left ventricle (LV) during the hospitalization and one year after ST segment elevation myocardial infarction (STEMI).Material and methods. The study included 120 patients with STEMI. There were following inclusion criteria: diagnosis of STEMI (2015 European Society of Cardiology guidelines); Killip £III acute heart failure (AHF); signed informed consent; patient age &gt;18 years old. There were following exclusion criteria: STEMI due to percutaneous coronary intervention or coronary artery bypass grafting; Killip IV AHF; patient age &gt;80 years; clinically significant comorbidities; death of the patient during the first day of hospitalization. On the 1st, 12th day of the disease and after a year all patients underwent echocardiography and the PICP concentration was determined. One year after myocardial infarction, contrast-enhanced cardiac magnetic resonance imaging was performed to assess CF. In the analyzed group of patients, on day 1 of STEMI, mean values of LV ejection fraction (EF) in the range of 40-49% were observed in 3 (2,5%) patients, LVEF &lt;40% — in 31 (26%), LVEF ≥50% — in 86 (71,7%). The final analysis was performed on a sample of patients with preserved LVEF (n=86) (71,7%).Results. On the first day of myocardial infarction, signs of DD were noted in 25 (29,1%) patients, while after 1 year, their number increased by 9 (10%) and amounted to 34 (39,5%) patients. In 15 (17,6%) people, worsening of myocardial systolic dysfunction was noted. Patients with a CF ³16% had the highest PICP expression on the first day of the disease. CF ≥16% one year after STEMI with preserved EF is associated with PICP concentration on day 1 of the disease. In addition, multidirectional correlations were revealed between the CF ≥16% and parameters of LV diastolic function (e’, mean pulmonary artery pressure, E/e’).Conclusion. Determination of the PICP concentration on the 1st day of myocardial infarction will allow early identification of patients at risk of CF one year after STEMI with preserved EF