Net Clinical Benefit

The net clinical benefit endpoint was chosen to capture total clinical value rather than potassium concentration alone, since binders are difficult to evaluate against treatments that shift potassium intracellularly. Median net clinical benefit at 6 hours was not statistically different between patiromer and placebo groups (−0.6 vs −0.4, p=0.44). The clinically meaningful threshold for net clinical benefit has not yet been established and requires validation in future studies. The net clinical benefit endpoint was first introduced as a post hoc analysis in the REDUCE pilot study. More negative net clinical benefit values indicate greater efficacy, reflecting larger potassium reduction with fewer additional interventions. Net clinical benefit is defined as the number of potassium-lowering interventions after initial treatment minus the change from baseline serum potassium in mEq/L.