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

O olhar dos e pelos cuidadores : os impactos de cuidar e a importância do apoio ao cuidador

Dissertação de mestrado em Intervenção Social, Inovação e Empreendedorismo, apresentada à Faculdade de Psicologia e Ciências da Educação e à Faculdade de Economia da Universidade de Coimbra, sob a orientação de Cristina Albuquerque.No âmbito do Mestrado em Intervenção Social, Inovação e Empreendedorismo, construiu-se esta tese de dissertação designada “O olhar dos e pelos cuidadores: os impactos de cuidar e a importância do apoio ao cuidador”. Numa ênfase teórica, diversos estudos referem que “burnout”, “burnot”, “sobrecarga”, condição geralmente associada a meios profissionais de “risco” ligados à saúde e à segurança, pode aplicar-se à exaustão física e mental que atinge uma parte significativa de cuidadores informais, tornando pertinente e prioritário reflectir sobre o cuidar e sobre os apoios, de acordo com o seu próprio olhar crítico. Nesse sentido, este trabalho partiu da questão: em que medida o apoio prestado aos cuidadores informais corresponde às suas reais expectativas e está de acordo com o que perspectivam como ideal na prestação de cuidados a dependentes? Começa por contextualizar a problemática da dependência, da prestação de cuidados em geral e seus impactos, recorrendo a fontes de informação diversas. Entretanto descreve o estudo empírico realizado no contexto geográfico do Concelho de Tondela, centrado no cuidador informal principal, primeiro descritivo e orientado para a obtenção de perfis de cuidadores informais que se salientam pela singularidade da sua situação, através de questionário; depois compreensivo, recorrendo à entrevista desse grupo mais restrito de cuidadores e à análise das narrativas individuais. A título de conclusão, pelo olhar dos cuidadores há distinção entre as respostas existentes e as desejáveis. E ao olhar pelos cuidadores, verifica-se que os apoios têm falhas na adequação aos seus contextos e circunstâncias de cuidar, dificultando o personalizar desses apoios e consequentemente dos cuidados

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.)