What can we learn from RELAX-AHF compared to previous AHF trials and what does the future hold?

Each year in the USA there are over 1 million hospital admissions directly related to heart failure (HF). With similar rates across Europe, this places a huge economic burden on healthcare systems globally. Hospitalisation for HF is associated with poor clinical outcomes with 25% of patients being readmitted with signs and symptoms of HF within 1 month of discharge and 10-20% dying in the 6 months after discharge. Although hospital admission could be a sign of disease progression, it is also possible that some of the treatments given acutely for example, inotropic therapy, may result in neurohormonal, haemodynamic and other effects accelerating end-organ damage and contributing to these poor outcomes after discharge. In contrast to the treatment of chronic heart failure (CHF), clinical trials conducted over the past decade in patients with acute HF (AHF) have failed to show significant reductions in morbidity or mortality despite some agents causing beneficial changes in symptoms. As such, the current treatment of patients hospitalised with HF is mainly based on consensus rather than clinical evidence and has changed little over time. We review RELAX-AHF in the context of the other key, large-scale AHF trials conducted over the past 15 years and compare and contrast study design and outcomes in an attempt to determine which factors might be associated with a successful trial in the future.