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Objectives. We sought to evaluate the current evidence for an effect of beta-blockade treatment on mortality in patients with congestive heart failure (CHF).Background. Although numerous small studies have suggested a benefit with beta-blocker therapy in patients with heart failure, a clear survival benefit has not been demonstrated. A recent combined analysis of several studies with the alpha- and beta-adrenergic blocking agent carvedilol demonstrated a significant survival advantage; however, the total number of events was small. Furthermore, it is unclear if previous studies with other beta-blockers are consistent with this finding.Methods. Randomized clinical trials of beta-blockade treatment in patients with CHF from January 1975 through February 1997 were identified using a MEDLINE search and a review of reports from scientific meetings. Studies were included if mortality was reported during 3 or more months of follow-up.Results. We identified 35 reports, 17 of which met the inclusion criteria. These studies included 3,039 patients with follow-up ranging from 3 months to 2 years. Beta-blockade was associated with a trend toward mortality reduction in 13 studies. When all 17 reports were combined, beta-blockade significantly reduced all-cause mortality (random effect odds ratio [OR] 0.69, 95% confidence interval [CI] 0.54 to 0.88). A trend toward greater treatment effect was noted for nonsudden cardiac death (OR 0.58, 95% CI 0.40 to 0.83) compared with sudden cardiac death (OR 0.84, 95% CI 0.59 to 1.2). Similar reductions in mortality were observed for patients with ischemic (OR 0.69, 95% CI 0.49 to 0.98) and nonischemic cardiomyopathy (OR 0.69, 95% CI 0.47 to 0.99). The survival benefit was greater for trials of the drug carvedilol (OR 0.54, 95% CI 0.36 to 0.81) than for noncarvedilol drugs (OR 0.82, 95% CI 0.60 to 1.12); however, the difference did not reach statistical significance (p = 0.10).Conclusions. Pooled evidence suggests that beta-blockade reduces all-cause mortality in patients with CHF. Additional trials are required to determine whether carvedilol differs in its effect from other agents.(J Am Coll Cardiol 1997;30:27–34)

BackgroundThe Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial found no difference in the primary outcome between warfarin and aspirin in 2305 patients with reduced left ventricular ejection fraction in sinus rhythm. However, it is unknown whether any subgroups benefit from warfarin or aspirin.Methods and resultsWe used a Cox model stepwise selection procedure to identify subgroups that may benefit from warfarin or aspirin on the WARCEF primary outcome. A secondary analysis added major hemorrhage to the outcome. The primary efficacy outcome was time to the first to occur of ischemic stroke, intracerebral hemorrhage, or death. Only age group was a significant treatment effect modifier (P for interaction, 0.003). Younger patients benefited from warfarin over aspirin on the primary outcome (4.81 versus 6.76 events per 100 patient-years: hazard ratio, 0.63; 95% confidence interval, 0.48-0.84; P=0.001). In older patients, therapies did not differ (9.91 versus 9.01 events per 100 patient-years: hazard ratio, 1.09; 95% confidence interval, 0.88-1.35; P=0.44). With major hemorrhage added, in younger patients the event rate remained lower for warfarin than aspirin (5.41 versus 7.25 per 100 patient-years: hazard ratio, 0.68; 95% confidence interval, 0.52-0.89; P=0.005), but in older patients it became significantly higher for warfarin (11.80 versus 9.35 per 100 patient-years: hazard ratio, 1.25; 95% confidence interval, 1.02-1.53; P=0.03).ConclusionsIn patients

Objectives. The aim of this study was to assess the efficacy of flosequinan in chronic heart failure. Background. Flosequinan is a new vasodilator drug that acts by interfering with the inositol-triphosphate/protein kinase C pathway, an important mechanism of vasoconstriction. The drug dilates both peripheral arteries and veins, is orally active and has a long duration of action that permits once-daily dosing. Previous studies have shown that flosequinan produces sustained hemodynamic benefits in heart failure, but large scale studies evaluating its clinical efficacy have not been reported. Methods. One hundred ninety-three patients with chronic heart failure (New York Heart Association functional class II or III and left ventricular ejection fraction

This paper details the substance and recommendations arising from a meeting convened by the National Heart, Lung, and Blood Institute in August 2009, to assess the challenges and opportunities of emergency department management of acute heart failure syndrome (AHFS). The assembled faculty represented a large cross section of medical professionals spanning the medical management continuum of patients presenting with acute heart failure and included heart failure cardiologists, emergency physicians, laboratory medicine specialists, nurses, and bench scientists. Their recommendations include proposals regarding the design and conduct of emergency department-based clinical trials, suggestions regarding the development of improved methods for early detection and monitoring of AHFS, and potential needs for expanding translational and applied AHFS focused research and biotechnology. We anticipate that this review will serve as a starting point for future investigations across the spectrum of funding sources.