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

Deprivation and excess winter mortality.

OBJECTIVE: To investigate the effect of material deprivation on the winter rise in mortality and temperature dependent variations in mortality. DESIGN: Ecological comparison of seasonal mortality at electoral ward level. Main outcome measures were ratios of winter to rest of the year mortality rates (seasonality ratios) and monthly deaths as the outcome variable in a model with monthly average temperature and Townsend score as main predictors. SETTING: Croydon, London, United Kingdom. SUBJECTS: All deaths of Croydon residents for the period 1990-1995. MAIN RESULTS: There was a clear relation between overall mortality and deprivation. There was no evidence of a relation between age and sex standardised seasonality ratios and Townsend scores for all deaths (Kendall's tau = -0.066, p = 0.63) or cardiovascular deaths or respiratory deaths. There was no evidence of an interaction between Townsend score and temperature in the model of ward mortality rates (p = 0.73). These findings were not affected by exclusion of deaths of nursing and residential home residents. CONCLUSION: This study provides no evidence of an effect of deprivation on excess winter mortality or temperature dependent variations in mortality. The findings question simple assumptions about the relation between deprivation and excess winter mortality and highlight the need for further study to guide interventions