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 < 100 mmHg (n = 1127), estimated glomerular filtration rate < 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

NMR spectroscopy reveals acetylsalicylic acid metabolites in the human urine for drug compliance monitoring.

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Long-term use of antiplatelet drugs is a well-studied therapy for the prevention of cardiovascular death. Ensuring compliance with lifelong administration of antiplatelet drugs, in particular acetylsalicylic acid, is one of the challenges of such therapy. The aim of this study is to explore the possibility of using nuclear magnetic resonance spectroscopy to identify acetylsalicylic acid metabolites in urine and to search for characteristic markers that could be used to detect patient compliance with long-term acetylsalicylic acid treatment

Assessing routine healthcare pattern for type 2 diabetes mellitus in Russia: the results of рharmacoepidemiological study (FORSIGHT-DM2)

Rationale. The rising incidence of type 2 diabetes mellitus (T2DM) allows researchers to conduct observational multicentre studies and obtain objective information about the epidemiology of diabetes and its complications and evaluate the efficacy of different therapies and diagnostic strategies designed to identify systemic vascular complications. Aims. To analyse epidemiological and socio-demographic parameters, the quality of glycaemic control, diagnostic monitoring and therapeutic measures typical among patients with T2DM living in Russian towns of different populations. Materials and methods. FORSIGHT-DM2 is an all-Russian multicentre observational epidemiological study that involves 2014 patients with T2DM from 45 different towns in the Russian Federation (RF). All patients have had T2DM for at least 1 year. They received glucose-lowering therapy and primary medical care from RF public outpatient health institutions between 01.01.2014 and 31.12.2014. For comparative analysis of the typical treatment for patients with T2DM, we stratified patients into groups based on the number of residents. Results. The data reveal a lack of glycaemic control (average НbА1с 7.9% ± 1.9%), with НbА1с  8% in 36% of patients. The frequency of T2DM complications was high and the prevalence of retinopathy was 63.2%, nephropathy was 34.4% (7.8% had chronic kidney disease G3a-G5), peripheral polyneuropathy was 63.3%, ‘diabetic foot’ syndrome was 13.7% and osteoarthropathy was 5%. The number of T2DM-related complications is correlated with the HbA1c level and disease duration. Moreover, simultaneous influence of these factors led to a significant increase in the number of chronic complications associated with T2DM (r = 0.338 for T2DM duration, r = 0.262 for HbA1c; р 0.001). Despite the high frequency of patient consultations with endocrinologists (83%) and a large percentage of hospitalisations in the current year (46%), the screening of chronic complications of T2DM in 2014 is insufficient. Conclusion. The results indicate insufficient glycaemic control among patients with T2DM and a higher prevalence of chronic complications compared with the national register of diabetic patients

Cost-of-Illness Analysis of Type 2 Diabetes Mellitus in the Russian Federation: Results from Russian multicenter observational pharmacoepidemiologic study of diabetes care for patients with type 2 diabetes mellitus (FORSIGHT-Т2DM)

Background: Cost-of-Illness Analysis (COI) constitutes the basis for the decision-making process on the budget and allocation in a modern health care system. Considering the wide prevalence of type 2 diabetes mellitus (Т2DM), it is important to perform COI in the Russian Federation (RF). Aim: The aim of the secondary objective FORSIGHT-Т2DM study was to conduct Cost-of-Illness Analysis (COI) of Т2DM in the Russian Federation in relation to taking into consideration the presence of complications and concomitant diseases. Materials and methods: COI of Т2DM was performed using the data obtained in Russian multicenter observational, pharmacoepidemiologic cross-sectional study of diabetes care for assessing routine healthcare pattern of T2DM in the Russian Federation (FORSIGHT-Т2DM). Information for each patient was collected from primary medical records and By asking patients to fill out a questionnaire. Total costs were calculated as the sum of direct medical costs (DCm), direct non-medical costs (DCn) and indirect costs (IC). Results: The final analysis included data from 2014 patients with T2DM residing in 45 cities of RF. Total direct medical costs (DCm) of treating Т2DM and its complications and comorbidities amounted to 105 337 rubles ($2742) per patient per year; direct non-medical costs (DCn) amounted to 24 518 rubles ($638) per patient per year; indirect costs (IC) amounted to 149 754 rubles ($3898) per patient per year. The total cost of T2DM in RF in 2014 year amounted to 279 609 rubles ($7278) per patient. The total cost of T2DM in RF in 2014 amounted to 279 609 rubles per patient. Conclusions: More than half (53,5%) of the total cost of T2DM is the loss of GDP due to patients disability. The DCm constitute 37,7% of the total cost of the disease, of which 57% is spent on treatment of T2DM complications and concomitant diseases, while only 10% is spent on glucose-lowering therapies

Spectral homogeneity of human platelets investigated by SERS.

This paper describes a detailed study of the spectral homogeneity of human platelets using Surface-enhanced Raman spectroscopy (SERS). We used a combined approach based on multivariate methods as principal component analysis and pair correlation algorithms to investigate platelets spectral properties. The correlation coefficients for each sample have been calculated, and the average coefficient of determination has been estimated. The high degree of spectral homogeneity inside one probe and between them has been revealed. The prospects of obtained results usage for pathologies based on platelet conformations during cardiovascular diseases have been demonstrated

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. CONCLUSION: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)