Expanding the outcomes in clinical trials of heart failure: the quality of life and economic components of EPHESUS (EPlerenone's neuroHormonal Efficacy and SUrvival Study).

BACKGROUND: Although quantification of the impact of treatment on survival remains the cornerstone of clinical research, the assessment of a broader range of disease outcomes is growing increasingly important. This manuscript provides an overview of the considerations made regarding quantification of a range of clinical and economic outcomes in the EPHESUS (EPlerenone's neuroHormonal Efficacy and SUrvival Study) study, a 6200-patient, randomized, controlled trial of aldosterone blockade in patients with heart failure as a complication of acute myocardial infarction.

METHODS AND RESULTS: Relevant clinical outcomes include disease progression (mortality, hospitalization), health status (symptoms, functioning, and quality of life), and costs. The primary hypothesis for the quality of life component of EPHESUS is that eplerenone will improve health status as defined by the Kansas City Cardiomyopathy Questionnaire summary score. In addition to the Kansas City Cardiomyopathy Questionnaire, the Short Form-12, the EuroQOL, the Medical Outcomes Study-Depression Scale and an Anxiety measure will be collected throughout the trial. Health care resource utilization including hospitalizations, emergency room visits, outpatient procedures and tests, and medications will also be collected. Analyses will estimate and describe the effect of aldosterone blockade on costs over time. If both the clinical effect and costs are greater for patients receiving aldosterone blockade, then eplerenone's cost-effectiveness will be estimated.

CONCLUSION: The EPHESUS trial has been designed to quantify a wide range of clinical outcomes. This broad range of data will allow a comprehensive assessment of the potential benefits of aldosterone blockade on patient health status and costs.