GLP-1 Agonist Therapy for Advanced Heart Failure With Reduced Ejection Fraction Design and Rationale for the Functional Impact of GLP-1 for Heart Failure Treatment Study

TLDR: By any metric, HF imposes a major public health and financial burden on society and the lack of new disease-modifying pharmacological therapy for HF over the past 2 decades further amplifies these concerns.

Abstract: Heart failure (HF) is a leading cause of mortality and morbidity in the industrialized world and imposes a substantial burden on public health. In the United States, HF is the primary cause of death for more than 60 000 people annually and a contributing factor in over 282 000 cases.1 Despite guideline-recommended therapy for patients with HF and reduced ejection fraction,1 the 1-year mortality in patients with New York Heart Association (NYHA) functional class III to IV HF on maximal medical therapy is 35% to 40%.2 Based on recent estimates, approximately 5.1 million adult Americans have HF, and projections show that by the year 2030 the prevalence of HF in the United States will increase by 25%.2 By any metric, HF imposes a major public health and financial burden on society. The lack of new disease-modifying pharmacological therapy for HF over the past 2 decades further amplifies these concerns. Hospitalization for acute HF syndrome (AHFS) is a significant predictor of increased mortality, recurrent hospitalization, increased resource consumption, impaired functional status, and worsened quality of life.3 Even after excluding patients with shock, several recent studies indicate that the rate of the composite end point of death or rehospitalization at 60 days post discharge is consistently >30% among patients hospitalized for AHFS.4–6 Although studies have identified some patient characteristics affecting the risk of this composite end point, no widely accepted risk prediction model has emerged to date.7 Previous large-scale studies have examined numerous interventions for preventing posthospitalization death or rehospitalization. Although some in-hospital treatments for AHFS have favorably affected in-hospital metrics, such as the rate of decongestion,8,9 or dyspnea scores,10 nearly all have failed to affect posthospitalization mortality or readmission or both. Included among these failed interventions are intravenous …