End points for clinical trials in acute heart failure syndromes

Abstract

Acute heart failure syndromes (AHFS) remain a major cause of morbidity and mortality, in part because the development of new therapies for these disorders has been marked by frequent failure and little success. The heterogeneity of current approaches to AHFS drug development, particularly with regard to end points, remains a major potential barrier to progress in the field. End points involving hemodynamic status, biomarkers, symptoms, hospital stay, end organ function, and mortality have all been employed either alone or in combination in recent randomized clinical trials in AHFS. In this review, we will discuss the various end point domains from both a clinical and a statistical perspective, summarize the wide variety of end points used in completed and ongoing AHFS studies, and suggest steps for greater standardization of end points across AHFS trials.

Figure 1. AHFS Episode Timeline

Timeline showing that end points might represent different portions of the time course of an acute heart failure syndrome (AHFS) episode and thus unique parts of the patient experience. BNP = B-type natriuretic peptide; HF = heart failure; PGA = patient-reported global assessment; Rx = treatment.