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

Digestible treonine levels in diets for lactation sows

Sessenta matrizes em lactação, de diferentes ordens de parto, foram utilizadas para avaliar o efeito de níveis de treonina digestível sobre o desempenho produtivo e reprodutivo, durante um período de lactação de 16,14 dias. Os animais foram distribuídos em delineamento inteiramente casualizado, com quatro tratamentos, quinze repetições por tratamento, sendo a porca considerada a unidade experimental. As rações experimentais foram constituídas de quatro níveis de treonina digestível, 0,608; 0,646; 0,684; 0,722 correspondentes a relações com a lisina digestível de 64, 68, 72 e 74%, respectivamente. Não se observou efeito dos níveis de treonina digestível da ração sobre os parâmetros produtivos e reprodutivos das porcas em lactação. Houve efeito dos tratamentos sobre o consumo de treonina digestível, que aumentou de forma linear. O ganho de peso dos leitões não foi influenciado pelos tratamentos. Concluiu-se que o nível de 0,608%, correspondente a relação treonina digestível:lisina digestível de 64%, atende as exigências de treonina digestível para porcas durante um período de lactação de 16,14 dias.Sixty lactating sows, with differents parities orders, were used to evaluate the effect of digestible threonine levels on the productive and reproductive performance, during period of lactation of 16.14 days. The animals were assigned to a randomized completely design, with four treatments and fifteen replicates. The sow was considered the experimental unity. The experimental diets were consisted of four levels of digestible threonine, 0.608; 0.646; 0.684; 0.722%, corresponding the ratios of digestible threonine:digestible lysine of 64, 68, 72 and 76%, respectively. No effects of digestible threonine levels of diets on productive and reproductive performance of sows were observed The intake of digestible threonine increased linearly among treatments. No effects of treatments were observed for weight gain of piglets. It can be concluded that the level of 0.608% of digestible threonine, corresponding of digestible threonine:digestible lysine ratio of 64% attend the requirements of digestible threonine of lactation sows, during period of lactation of 16.14 days.Coordenação de Aperfeiçoamento de Pessoal de Nível Superio

Treonina digestível em rações para matrizes suínas em lactação

Sessenta matrizes suínas pluríparas (média de quatro partos) de linhagem comercial, com peso inicial de 262,7 ± 22,50 kg, foram utilizadas para avaliar o efeito de níveis de treonina digestível sobre os desempenhos produtivo e reprodutivo durante 16,02 ± 1,17 dias de lactação. Os animais foram distribuídos em delineamento inteiramente casualizado, com 4 tratamentos e 15 repetições, considerando a matriz a unidade experimental. As rações foram formuladas com quatro níveis de treonina digestível (0,608; 0,646; 0,684 ou 0,722%, correspondentes a relações de 64, 68, 72 e 76%, respectivamente, com a lisina digestível). Os níveis de treonina digestível avaliados não influenciaram o consumo diário de ração, que foi de 4,7 kg/animal. O consumo diário individual de treonina digestível variou de forma linear entre os níveis de treonina testados. Não houve efeito dos níveis de treonina digestível da ração sobre os desempenhos produtivo e reprodutivo das porcas em lactação. O nível de 0,608%, correspondente à relação treonina digestível:lisina digestível de 64%, atende às exigências de treonina digestível de matrizes suínas durante a lactação

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.)