Net clinical benefit of patiromer for acute hyperkalemia: a post-hoc analysis of the reduce trial

Hyperkalemia (HK) is a common and potentially life-threatening electrolyte disturbance managed with potassium (K)-shifting medications and potassium binders. The use of K-shifting agents is a confounder when assessing the effects of K-binding treatments in clinical trials. Patiromer is a K-binding agent with demonstrated efficacy for the management of chronic hyperkalemia. As both changes in sK level and the number of interventions required to lower potassium are clinically relevant, we propose an evaluation using Net Clinical Benefit (NCB), defined as the number of K shifting interventions less the numerical change in K.

We conducted a post-hoc analysis of the REDUCE trial to determine the NCB of patients with hyperkalemia in the ED setting. Patients were randomized to the standard of care (SOC) or patiromer plus standard of care (PAT). Serum potassium and HK-related interventions were recorded. NCB, defined as the number of K shifting interventions less the numerical change in K, with lower numbers showing a greater benefit, was calculated at 2, 4, and 6 h for the standard of care (SOC) and patiromer (PAT) groups.

Of the 43 patients randomized, 30 completed 4 h of study intervention and were included in the analysis, including 15 each in the SOC and PAT arms. NCB for PAT over SOC was numerically superior at 2 h (-0.05 vs 0.43; p = 0.108), 4 h (0.11 vs 0.73; p = 0.097), and 6 h (0.64 vs 1.60; p = 0.094) post-intervention.

NCB captures the clinical benefit of binders, while accounting for the confounding effect of other potassium-lowering agents.