Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

FAMILIAL HYPERCHOLESTEROLEMIA: DIAGNOSTIC ISSUES AND THERAPEUTIC POSSIBILITIES

Familial hypercholesterolemia (FHC) is a common monogenic disease that occurs with a frequency of ~1:250 and is characterised by a high content of low-density lipoprotein (LDL) in the blood. This disease leads to the early development of atherosclerotic cardiovascular diseases (ACVD). Although the screening and diagnostics issues concerned with FHC are well developed and the modern lipid-lowering therapy can significantly improve the prognosis, the detectability of this disease remains extremely low. In recent years, the concept of FHC has undergone significant changes under the influence of large epidemiological studies, including verification of the FHC diagnosis using genetic tests. The article is aimed at discussing the clinical manifestations of FHC, as well as modern medical and extracorporal approaches to its treatment.Conclusion. Until the advent of modern lipid-lowering drugs, FHC had remained to be a disease with a poor prognosis due to early ACVD and the associated premature death. Today, the diseases is amenable to successful treatment, which, though not eliminating the genetic defect, allows almost the same life duration as in the general population to be achieved. However, all the possibilities of modern approaches to the treatment of this serious disease can be realized provided that a state-level screening program for such patients has been implemented.Conflict of interest: the authors declare no conflict of interest

FAMILIAL HYPERCHOLESTEROLEMIA: DIAGNOSTIC ISSUES AND THERAPEUTIC POSSIBILITIES

Familial hypercholesterolemia (FHC) is a common monogenic disease that occurs with a frequency of ~1:250 and is characterised by a high content of low-density lipoprotein (LDL) in the blood. This disease leads to the early development of atherosclerotic cardiovascular diseases (ACVD). Although the screening and diagnostics issues concerned with FHC are well developed and the modern lipid-lowering therapy can significantly improve the prognosis, the detectability of this disease remains extremely low. In recent years, the concept of FHC has undergone significant changes under the influence of large epidemiological studies, including verification of the FHC diagnosis using genetic tests. The article is aimed at discussing the clinical manifestations of FHC, as well as modern medical and extracorporal approaches to its treatment.Conclusion.Until the advent of modern lipid-lowering drugs, FHC had remained to be a disease with a poor prognosis due to early ACVD and the associated premature death. Today, the diseases is amenable to successful treatment, which, though not eliminating the genetic defect, allows almost the same life duration as in the general population to be achieved. However, all the possibilities of modern approaches to the treatment of this serious disease can be realized provided that a state-level screening program for such patients has been implemented.Conflict of interest: the authors declare no conflict of interest.</jats:p

Predictors of repeat myocardial revascularization for the long-term after percutaneous coronary interventions in patients with combination of coronary artery disease and chronic obstructive pulmonary disease

Aim. To assess the influence of concomitant chronic obstructive pulmonary disease (COPD) on the frequency of repeat myocardial revascularization in patients with coronary artery disease (CAD) after percutaneous coronary interventions (PCI), as well as to determine independent predictors of repeat revascularization in patients with concominant COPD. Materials and methods. A prospective cohort study included 646 patients with CAD, of which 254 had concominant COPD. All patients underwent PCI (46.9% for acute coronary syndrome in the main group and 44.9% in the control group. Remaining interventions were elective). The frequency of repeat myocardial revascularization and the time till re-intervention was registered during the follow-up period up to 36 months. Results. COPD increases risk of repeat myocardial revascularization (hazard ratio - HR 1.46; 95% confidence interval - CI 1.03-2.06), repeat PCI (HR 1.62; 95% CI 1.03-2.32) and is accompanied by an earlier onset of re-intervention. An independent predictors of repeat myocardial revascularization in the Cox regression model are: glomerular filtration rate (p=0.001), ankle-brachial index (p=0.004), frequent exacerbations of COPD (p=0.028), total number of coronary artery stenosis (p=0.039) and blood concentration of C-reactive protein (p=0.066). Conclusions. COPD is a significant risk factor of re-intervention after PCI in patients with acute and chronic forms of CAD and leads to its earlier performing. The patients with frequent COPD exacerbations have the highest risk of repeat myocardial revascularization during follow-up.</jats:p

Vagus Nerve Stimulation for Treatment of Chronic Heart Failure

Background: Heart failure is the outcome of most cardiovascular diseases. Its prevalence continues to increase annually, which emphasizes the importance of developing therapeutic strategies to prevent adverse outcomes. This article reviews current data on the effect of vagus nerve stimulation on the course of chronic heart failure.Objective: To summarize available literature data on the effect of vagus nerve stimulation on the course of chronic heart failure.Materials and methods: We searched PubMed and eLIBRARY for the relevant information over the last 20 years using the following keywords: vagus nerve, heart failure, stimulation, ejection fraction. The search was performed by titles, abstracts, and keywords.Results: This review revealed that vagus nerve stimulation has favorable effects in patients with heart failure and warrants further careful investigation

TSH-secreting pituitary adenoma: late diagnosis and effectiveness of therapy

Современные лечебно-диагностические алгоритмы позволяют своевременно выявить нарушения функции щитовидной железы, назначить адекватное лечение. Между тем в процессе интерпретации тиреоидного статуса необходимо учитывать крайне редкую, но реально существующую возможность развития тиреотоксикоза центрального генеза, диагностика которого, как показывает общемировая практика, затруднена.&#x0D; Представлен клинический случай ТТГ-продуцирующей аденомы гипофиза у женщины 47 лет, длительное время получающей тиреостатики по поводу тиреотоксикоза. Пациентке был установлен диагноз болезнь Грейвса, однако истинной причиной тиреотоксикоза являлась тиреотропинома. Основные лабораторные проявления тиреотоксикоза центрального генеза заключались в сочетании эпизодов нормального или повышенного уровня ТТГ с высокой или нормальной концентрацией свободного Т4. При МРТ выявлена макроаденома гипофиза. Наличие клинических проявлений тиреотоксикоза позволило исключить синдром резистентности к тиреоидным гормонам. Пробное лечение октреотидом купировало клинические и лабораторные проявления тиреотоксикоза, что обусловило выбор консервативного метода в качестве первой линии терапии. Обсуждаются особенности клинико-лабораторных проявлений, а также принципы дифференциальной диагностики и современных методов лечения ТТГ-продуцирующих аденом гипофиза.</jats:p

Risk Stratification after an Acute Coronary Syndrome: Significance of Antithrombotic Therapy

The impact of the de-escalation strategy of antiplatelet therapy (APT) on the life expectancy after acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI) requires an assessment in real clinical practice. Into the Russian multicentral observational trial (ORACLE II ClinicalTrials.gov number, NCT04068909), 1803 patients with ACS and PCI indications were enrolled. During 12 months of follow-up, 228 all-cause deaths have occurred. The analysis of death predictors was carried out by the classification tree method. Age, an option of antithrombotic therapy, a history of chronic heart failure, and uric acid level had the greatest prognostic value. The death prediction model’s sensitivity was 82.1% in the training cohort and 79.2% in the test cohort. During the observation period, ticagrelor was replaced with clopidogrel (APT de-escalation) in 357 patients. The groups of patients with different antiplatelet therapy options were adjusted for clinical parameters by the pseudorandomization method. The de-escalation group had the lowerest all-cause death rate. The incidence of bleeding and recurrent nonfatal coronary events in the study groups did not differ significantly. Thus, the APT regimen’s advantage of changing from the maximum in the first weeks after ACS to moderate at follow-up has been confirmed. There is an obvious need to study the possibilities of individualizing antiplatelet therapy in patients after acute coronary syndromes.</jats:p

Risk Stratification after an Acute Coronary Syndrome: Significance of Antithrombotic Therapy

The impact of the de-escalation strategy of antiplatelet therapy (APT) on the life expectancy after acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI) requires an assessment in real clinical practice. Into the Russian multicentral observational trial (ORACLE II ClinicalTrials.gov number, NCT04068909), 1803 patients with ACS and PCI indications were enrolled. During 12 months of follow-up, 228 all-cause deaths have occurred. The analysis of death predictors was carried out by the classification tree method. Age, an option of antithrombotic therapy, a history of chronic heart failure, and uric acid level had the greatest prognostic value. The death prediction model’s sensitivity was 82.1% in the training cohort and 79.2% in the test cohort. During the observation period, ticagrelor was replaced with clopidogrel (APT de-escalation) in 357 patients. The groups of patients with different antiplatelet therapy options were adjusted for clinical parameters by the pseudorandomization method. The de-escalation group had the lowerest all-cause death rate. The incidence of bleeding and recurrent nonfatal coronary events in the study groups did not differ significantly. Thus, the APT regimen’s advantage of changing from the maximum in the first weeks after ACS to moderate at follow-up has been confirmed. There is an obvious need to study the possibilities of individualizing antiplatelet therapy in patients after acute coronary syndromes