Patiromer Efficacy across Kidney Function and Hyperkalemia Subgroups in Heart Failure and Reduced Ejection Fraction:...

In the DIAMOND (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure) trial, patiromer enabled optimization of renin-angiotensin-aldosterone system inhibitors (RAASi) for patients with heart failure and reduced ejection fraction (HFrEF) and current or recent hyperkalemia. Impaired kidney function substantially increases hyperkalemia risk due to impaired potassium excretion. Therefore, in this post hoc analysis, we examined the efficacy of patiromer across baseline kidney function and hyperkalemia subgroups.

We classified all patients randomized to patiromer (N=439) or placebo (N=439), after successful run-in optimization, into 4 subgroups according to estimated glomerular filtration rate (eGFR) <45 vs ≥45 mL/min/1.73m2 (trial eligibility criterion: ≥30 mL/min/1.73m2) and baseline hyperkalemia (≤5.0 vs >5.0 mEq/L; trial required K >5.0 or prior RAASi discontinuation for hyperkalemia).

Patiromer reduced adjusted mean change in serum potassium (primary outcome) across all subgroups, with the largest effect in patients with eGFR <45 mL/min/1.73m2 and hyperkalemia (-0.28 mEq/L, 95% CI -0.38 to -0.18, P<0.001) and the smallest in those with eGFR ≥45 mL/min/1.73m2 and normokalemia (-0.08 mEq/L, 95% CI -0.12 to -0.04, P<0.001; Pinteraction <0.001). Patiromer reduced time-to-first hyperkalemia consistently across subgroups. Patients with eGFR <45 mL/min/1.73m2 and baseline hyperkalemia derived the numerically greatest effect in prevention of mineralocorticoid receptor antagonist down-titration (hazard ratio 0.39, 95% CI 0.18-0.84, P=0.02) and had the highest win ratio for hyperkalemia-related morbidity-adjusted outcomes (3.03, 95% CI 1.96-4.70, P<0.001). However, Pinteraction values for these secondary endpoints were not statistically significant.

Patiromer reduced serum potassium across baseline kidney function and hyperkalemia subgroups, with greater effect in patients with reduced kidney function and baseline hyperkalemia. These findings suggest potential heterogeneity in potassium-lowering effects of patiromer across subgroups, although the analysis is exploratory and should be considered hypothesis-generating.