Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin.

Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, −0.7 percentage points; 95% confidence interval [CI], −2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, −0.4 percentage points; 95% CI, −1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.)

Background— Although previous work has suggested that anemia is associated with an increased mortality in selected patients with congestive heart failure (CHF), little is known about the prevalence and predictors of anemia, or whether anemia is an independent prognostic factor in unselected, community-based patients with CHF. Methods and Results— We analyzed a population-based cohort of patients with new-onset CHF from a database of patients discharged from 138 acute-care hospitals in Alberta, Canada, between April 1993 and March 2001. Logistic regression, Kaplan-Meier survival analyses, and Cox proportional hazards model were used. Among the 12 065 patients with CHF (median age 78 years), 17% had anemia, 58% of whom had anemia of chronic disease. After adjustment for clinical and demographic variables, patients with anemia were more likely to be older (odds ratio [OR] 1.01 per year) and female (OR 1.2 [95% confidence interval 1.1 to 1.3]) and to have a history of chronic renal insufficiency (OR=3.2 [95% confidence interval 2.8 to 3.6]), or hypertension (OR 1.3 [95% confidence interval 1.2 to 1.5]). Hazard ratios for mortality, adjusting for covariates, were 1.34 (1.24 to 1.46) in anemic patients, and 1.36 (1.23 to 1.50) in those patients with anemia of chronic disease. Conclusions— In this large cohort of community-dwelling patients with CHF, anemia is common and an independent prognostic factor for mortality. Further research into the mechanisms of anemia in CHF and randomized controlled trials to test whether correction of anemia improves prognosis in CHF are needed.

Background— The prevalence, prognostic import, and impact of renal insufficiency on the benefits of ACE inhibitors and β-blockers in community-dwelling patients with heart failure are uncertain. Methods and Results— We analyzed data from a prospective cohort of 754 patients with heart failure who had ejection fraction, serum creatinine, and weight measured at baseline. Median age was 69 years, and 43% had an ejection fraction ≥35%. By the Cockcroft-Gault equation, 118 patients (16%) had creatinine clearances ≤30 mL/min and 301 (40%) had creatinine clearances between 30 and 59 mL/min. During follow-up (median 926 days), 385 patients (37%) died. Even after adjustment for all other prognostic factors, survival was significantly associated with renal function ( P =0.002) in patients with either systolic or diastolic dysfunction; patients exhibited a 1% increase in mortality for each 1-mL/min decrease in creatinine clearance. The associations with 1-year mortality reductions were similar for ACE inhibitors (OR 0.46 [95% CI 0.26 to 0.82] versus OR 0.28 [95% CI 0.11 to 0.70]) and β-blockers (OR 0.40 [95% CI 0.23 to 0.70] versus OR 0.41 [95% CI 0.19 to 0.85]) in patients with creatinine clearances <60 mL/min versus ≥60 mL/min, although these drugs were used less frequently in patients with renal insufficiency. Conclusions— Renal insufficiency is more prevalent in patients with heart failure than previously reported and is an independent prognostic factor in diastolic and systolic dysfunction. ACE inhibitors and β-blockers were associated with similar reductions in mortality in patients with and without renal insufficiency.

Heart failure is the fastest growing cardiovascular diagnosis in the United States, with a community prevalence of 2.5% in adults, and the direct and indirect costs of heart failure exceed $33 billion per year.¹ Quiz Ref ID Despite many advances in diagnosis and pharmacotherapy for heart failure during the past 2 decades, morbidity and mortality remain high and quality of life is poor for many patients. Thus, there is increasing enthusiasm for the therapeutic potential of atrial-synchronized biventricular pacemakers (cardiac resynchronization therapy [CRT]) in patients with heart failure and left ventricular (LV) systolic dysfunction. CRT is designed to eliminate the delay in activation of the LV free wall found in many patients with LV systolic dysfunction and thereby improves mechanical synchrony, which in turn increases LV filling time, reduces mitral regurgitation, and reduces septal dyskinesis.