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

Self-education and self-management to develop entrepreneurship competence in future professionals

The relevance of this article lies in the need to improve the process of developing competences future professionals need to develop self-employment skills under the conditions of the socio-economic crisis and the instability of the Ukrainian labour market. The article aims to prove the need for systematic implementation of self-education and self-management technologies in Ukrainian professional education schools to develop entrepreneurship competence in future professionals. Research methods include a survey and an analysis of documentary information. Ukraine strives to increase the importance of young people's readiness for lifelong learning. However, the article finds that most students do not have sufficient psychological knowledge and selfmanagement skills for successful self-development and self-employment. The development of entrepreneurship competence is, for the first time, justified through the systemic implementation of self-education and selfmanagement technologies in the educational process of professional education schools. The article presents a pedagogical technology for developing entrepreneurship competence in future professionals through selfmanagement. Besides, it offers the most effective forms of its introduction (psychology workshops, video lectures, electronic portfolios) and singles out the optimal conditions of their use. The level of the technology's readiness is IRL5 (the efficiency was proven at the level of experimental educational institutions). Success in its implementation depends on the regulatory recognition of the role of the social and humanities-related component in professional education; the incorporation of a self-management course in all programmes for training, retraining and advanced training of psychology and teaching staff; the encouragement of teaching staff to effectively use the described technologies in the educational process; systematic training of students to implement self-education and self-management as the technologies of success

Technologizing youth training for entrepreneurship to fulfil sustainable development goals

The relevance of the article can be justified by the requirements for youth entrepreneurship training defined by sustainable development goals. In particular, these requirements are expected to promote the continuous, comprehensive and sustainable economic growth of the country, as well as full and decent employment for all. The object of the research is the technologization of youth training for entrepreneurship. The aim of the research lies in justifying and experimentally verifying the author’s method of introducing pedagogical technologies in youth training for entrepreneurship in vocational education institutions. Results: the author’s method of introducing pedagogical technologies is defined as a system of dependent variables, pedagogical factors and algorithms of their application. The article also presents a modelled algorithm of the simultaneous introduction of the author’s technologies (motivating future specialists towards business activity, improving their financial literacy and capacity for project activity and effective self-management) in educational institutions. The effectiveness of this method has been verified during a pedagogical experiment. This experiment aimed to prove the positive dynamics in the levels of future specialists’ entrepreneurship competence. Conclusions: In the short run, the author’s method of introducing pedagogical technologies in youth training for entrepreneurship allows one to optimize teachers’ activities (by simplifying the choice of pedagogical influence factors and isolating dependent variables), strengthen the systematicity, controllability, reproducibility and effectiveness of the author’s technologies. In the medium run, it will promote the technologicalization of vocational education and help achieve sustainable development goals. Experimental verification of the author’s method has shown a significant increase in students’ levels of entrepreneurship competence. Furthermore, it has proved the synergistic effect of the systematic use of innovative forms and methods of pedagogical influence on personality

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.)