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

Assessing Soil Salinity Risk in the RUT Irrigation District, Colombia

Abstract The water resources mismanagement is a common concern in the agriculture, and this issue is boosting salinity processes in the Colombian lands. Thus, this paper aimed to assess the soil salinity risk in the RUT irrigation district for sugarcane, grape, and passion fruit by coupling SOSALRIEGO-GIS. First, sources of surface water and their influence areas were identified in the RUT irrigation district. Afterwards, inputs (water ionic constituents, electrical conductivity of rainwater, annual rainfall, crop salt tolerance, soil texture, and leaching fraction) fed in the SOSALRIEGO model, and then, the leaching requirement (LR) of each zone was computed (output) for each crop. Finally, employing GIS, LR values were arranged in categories in order to map the soil salinity risk in the RUT irrigation district for each crop and zone. The soil salinity risk fell into a medium rank for sugarcane, medium to high ranks for grape, and high to very high ranks for passion fruit. Furthermore, the soil salinity risk was higher in zones with poor irrigation water quality. Zones II and III, which canals convey domestic wastewater and drained water fell in greater salinity risk category than zone I, which bears water withdrawal from the Cauca River.Resumo A inadequada gestão dos recursos hídricos é uma preocupação comum na agricultura, este fato está impulsando processos de salinização nos solos da Colômbia. Portanto, esta pesquisa objetivou avaliar o risco da salinização dos solos no distrito de irrigação RUT às culturas de cana-de-açúcar, uva e maracujá; integrando o modelo SOSALRIEGO com os Sistemas de Informações Geográficas (SIG). Em primeiro lugar, os parâmetros de entrada (composição iônica da água de irrigação, condutividade elétrica da água de precipitação, precipitação anual, tolerância das culturas à salinidade, culturas, textura do solo e eficiência de lavado de sais) alimentaram o modelo SOSALRIEGO e, seguidamente o requerimento de lavado de sais (RL) foi calculado. Finalmente, usando os SIG, os valores de RL foram categorizados com o objetivo de mapear o risco de salinização dos solos na área de estudo para cada cultura em cada zona. O risco de salinização foi classificado como Médio para a cultura da cana-de-açúcar, Médio a Elevado para a cultura da uva, e Elevado a Muito Elevado para o maracujá. Além disso, o risco de salinização foi maior nas zonas com menor qualidade da água de irrigação. As zonas II e III, cujos canais conduzem águas residuais e de drenagem foram qualificados em categorias maiores de risco do que a zona I, a qual extrai a água diretamente do Rio Cauca.Resumen La inadecuada gestión de los recursos hídricos es una preocupación común en la agricultura, y este hecho está impulsando procesos de salinización en los suelos de Colombia. Por lo tanto, este trabajo tuvo como objetivo evaluar el riesgo de salinización del suelo en el distrito de riego RUT para cultivos de caña de azúcar, uva, maracuyá integrando el modelo SOSALRIEGO con SIG. En primer lugar, se identificaron las fuentes hídricas y sus áreas de influencia. Posteriormente, los parámetros de entrada (composición iónica del agua, conductividad eléctrica del agua de lluvia, precipitación anual, tolerancia de cultivos a la salinidad, cultivos, textura del suelo y la eficiencia de lavado) alimentaron el modelo SOSALRIEGO y, a continuación, el Requerimiento de Lavado de sales (RL) fue calculado para cada cultivo. Por último, utilizando SIG, los valores RL se organizaron en categorías con el fin de mapear el riesgo de salinización del suelo en el distrito de riego RUT para cada cultivo en cada zona. El riesgo de salinización se clasificó como medio para caña de azúcar, medio a Alto para la uva, y alto a muy alto para maracuyá. Además, el riesgo salinización del suelo encontrado fue mayor en zonas con baja calidad del agua de riego. Las Zonas II y III, en las cuales los canales conducen aguas residuales domésticas y el agua drenada fueron calificados en categorías superiores de riesgo de salinización que la Zona I, la cual recibe agua extraída directamente del río Cauca

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events

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.)