Changes in natriuretic peptide levels following patiromer-enabled optimization of medical therapy in heart failure: A post hoc analysis of the DIAMOND study

Aims: In the DIAMOND (Patiromer for the Management of Hyperkalaemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure) trial, the potassium binder patiromer enabled optimization of renin–angiotensin–aldosterone system inhibitors (RAASi) for patients with heart failure and a reduced ejection fraction (HFrEF) and current or recent hyperkalaemia. In this post-hoc analysis, we evaluated the effect of patiromer-enabled RAASi optimization on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, an established surrogate endpoint for clinical outcomes in HFrEF. Methods and results: During screening, 539 (61.4%) of the 878 subsequently randomized patients had NT-proBNP ≥1000 pg/ml, measured prior to a 12-week run-in period on single-blinded patiromer during which RAASi were optimized. Among these patients, 165/266 (62%) in the patiromer and 172/273 (63%) in the placebo arm had follow-up NT-proBNP. For these 337 patients, we evaluated the change in NT-proBNP from screening to week 18 after randomization. NT-proBNP declined by −53% (95% confidence interval −59% to −46%; p < 0.001) in both arms combined (median absolute change: −731 [−1832, 107] pg/ml), with no significant difference between the two arms (p = 0.135). A >30% NT-proBNP reduction was observed in 93/165 (56%) patiromer and 88/172 (51%) placebo patients (p = 0.38), whereas 60/165 (36%) and 53/172 (31%), respectively, achieved NT-proBNP levels <1000 pg/ml at week 18 (p = 0.30). Conclusions: In this post-hoc analysis of DIAMOND, patients with HFrEF and elevated (>1000 ng/ml) NT-proBNP at screening experienced clinically meaningful NT-proBNP reductions following a RAASi optimization strategy that included patiromer during the run-in phase, with no significant differences observed between patiromer and placebo groups during the randomized withdrawal phase.