Omecamtiv Mecarbil in Black Patients With Heart Failure and Reduced Ejection Fraction: Insights From GALACTIC-HF.

BACKGROUND: Omecamtiv mecarbil improves cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Consistency of drug benefit across race is a key public health topic. OBJECTIVES: The purpose of this study was to evaluate the effect of omecamtiv mecarbil among self-identified Black patients. METHODS: In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) patients with symptomatic HF, elevated natriuretic peptides, and left ventricular ejection fraction (LVEF) ≤35% were randomized to omecamtiv mecarbil or placebo. The primary outcome was a composite of time to first event of HF or cardiovascular death. The authors analyzed treatment effects in Black vs White patients in countries contributing at least 10 Black participants. RESULTS: Black patients accounted for 6.8% (n = 562) of overall enrollment and 29% of U.S. enrollment. Most Black patients enrolled in the United States, South Africa, and Brazil (n = 535, 95%). Compared with White patients enrolled from these countries (n = 1,129), Black patients differed in demographics, comorbid conditions, received higher rates of medical therapy and lower rates of device therapies, and experienced higher overall event rates. The effect of omecamtiv mecarbil was consistent in Black vs White patients, with no difference in the primary endpoint (HR = 0.83 vs 0.88, P-interaction = 0.66), similar improvements in heart rate and N-terminal pro-B-type natriuretic peptide, and no significant safety signals. Among endpoints, the only nominally significant treatment-by-race interaction was the placebo-corrected change in blood pressure from baseline in Black vs White patients (+3.4 vs -0.7 mm Hg, P for interaction = 0.02). CONCLUSIONS: GALACTIC-HF enrolled more Black patients than other recent HF trials. Black patients treated with omecamtiv mecarbil had similar benefit and safety compared with White counterparts.

Significance of hyponatremia in heart failure.

Heart failure is one of the most common, costly, disabling and growing diseases (McMurray and Pfeffer in Lancet 365(9474):1877-1889, 2005). Hyponatremia, conventionally defined as a serum-sodium concentration equal or less than 135 mmol/l (American Heart Association in Heart disease and stroke statistics--2007 update. American Heart Association, Dallas, 2007; Stewart et al. in Eur J Heart Fail 4:361-371, 2002), is a common phenomenon in patients with heart failure, with an incidence of 20-25% (Krumholz et al. in Arch Intern Med 157:e99-e104, 1997; Rosamond et al. in Circulation 117(4):e25-e146, 2008; Adrogue and Madias in N Engl J Med 342:1581-1589, 2000) and seems to be of prognostic importance in patients with heart failure (Luca et al. in Am J Cardiol 96:19L-23L, 2005; Gheorghiade et al. in Eur Heart J 28:980-988, 2007; Gheorghiade et al. in Arch Intern Med 167:1998-2005, 2007). So far treatment strategies have been limited and burdened by side effects. The development of hyponatremia in the setting of heart failure is related to the arginine vasopressin (AVP) dysregulation. Thus, AVP receptor antagonists are a promising approach to treatment. However, several questions remain: whether there is a cause-and-effect mechanism, if the correction of hyponatremia improves outcomes, and defining the specific cut-off level of serum-sodium that should be used to define hyponatremia. In this review, we aim to summarize the literature on hyponatremia in patients with heart failure within several aspects: incidence in clinical trials and registries, prognostic value, underlying mechanisms, therapeutic options, and possible future perspectives.

Prospective assessment of the occurrence of anemia in patients with heart failure: results from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry.

BACKGROUND: Although a potentially important pathophysiologic factor in heart failure, the prevalence and predictors of anemia have not been well studied in unselected patients with heart failure. METHODS: The Study of Anemia in a Heart Failure Population (STAMINA-HFP) Registry prospectively studied the prevalence of anemia and the relationship of hemoglobin to health-related quality of life and outcomes among patients with heart failure. A random selection algorithm was used to reduce bias during enrollment of patients seen in specialty clinics or clinics of community cardiologists with experience in heart failure. In this initial report, data on prevalence and correlates of anemia were analyzed in 1,076 of the 1,082 registry patients who had clinical characteristics and hemoglobin determined by finger-stick at baseline. RESULTS: Overall (n = 1,082), the registry patients were 41% female and 73% white with a mean age (+/-SD) of 64 +/- 14 years (68 +/- 13 years in community and 57 +/- 14 years in specialty sites, P < .001). Among the 1,076 patients in the prevalence analysis, mean hemoglobin was 13.3 +/- 2.1 g/dL (median 13.2 g/dL); and anemia (defined by World Health Organization criteria) was present in 34%. Age identified patients at risk for anemia, with 40% of patients >70 years affected. CONCLUSIONS: Initial results from the STAMINA-HFP Registry suggest that anemia is a common comorbidity in unselected outpatients with heart failure. Given the strong association of anemia with adverse outcomes in heart failure, this study supports further investigation concerning the importance of anemia as a therapeutic target in this condition.