Heart failure is a clinical syndrome associated with abnormality of cardiac structure and function, leading to progressive symptoms such as dyspnea and fatigue, but even stable patients with mild symptoms may have relatively high risk of hospitalization and death.1,2
* EMPHASIS was a randomized, double-blind, placebo-controlled trial of 2737 patients at least 55 years of age. Patients received eplerenone (up to 50 mg daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure.6
† The CHARM Low–Left Ventricular Ejection Fraction (LVEF) trials were two randomized, parallel, placebo-controlled trials (CHARM-Alternative, for patients who cannot tolerate ACE inhibitors, and CHARM-Added, for patients who were receiving ACE inhibitors). Mortality and morbidity were determined in 4576 low (≤40%) LVEF patients (2289 candesartan and 2287 placebo), titrated as tolerated to a target dose of 32 mg once daily, and observed for 2 to 4 years (median, 40 months). The primary outcome (time to first event by intention to treat) was cardiovascular death or heart failure hospitalization for each trial, in the pooled analysis of the low LVEF trials.7
‡ An analysis of 6 trials/registries comprising over 10,000 heart failure patients followed for a mean of 1.6 years evaluated the Seattle Heart Failure model and its relationship to NYHA class for predicting mode of death. A key finding was that sudden death accounted for 65% of all deaths in NYHA class II patients. In a posthoc analysis of data from a randomized trial of nearly 4000 heart failure patients, the proportion of patients who died from worsening heart failure increased with NYHA class.8
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