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

Abstract

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.

Keywords: Guideline‐directed medical therapy; Heart failure with reduced ejection fraction; Hyperkalaemia; NT‐proBNP; Patiromer; Therapy optimization.