Oral Diuretic Intensification as a Worsening Heart Failure Event in the Primary Outcome of Clinical Trials

AbstractAlthough evidence-based therapies for patients with heart failure (HF) have decreased all-cause mortality, the residual risk of other clinically relevant outcomes - such as worsening HF - remains high. In this context, contemporary HF trials have increasingly employed composite primary outcomes that include worsening HF, commonly defined as episodes resulting in hospitalization for HF or urgent ambulatory visits with use of intravenous HF pharmacotherapies. In this Clinical Trials Workshop, we propose that the definition of worsening HF in clinical trials be expanded to include HF episodes treated with ambulatory oral diuretic intensification (ODI). Using previously reported post hoc analyses of pharmacotherapy trials in chronic HF, we highlight the prognostic significance of ODI and examine the implications of including ODI on anticipated event rates and estimated treatment effect. We propose a standardized definition of ODI and discuss challenges and regulatory considerations of incorporating ODI into HF trial end points.