Introduction and methods

PATIROMER FOR THE MANAGEMENT OF HYPERKALEMIA IN HEART FAILURE PATIENTS WITH REDUCED EJECTION FRACTION RECEIVING RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM INHIBITORS: RESULTS FROM A PRESPECIFIED ANALYSIS BY EGFR FROM THE DIAMOND TRIAL

Presented at ERA congress 2022 in Paris, France by Patrick Rossignol (Vandœuvre-lès-Nancy, France)

Hyperkalemia in patients with HF with or without CKD may lead to suboptimal use of RAASi therapy. In the DIAMOND trial , patiromer was initiated in patients with hyperkalemic events and using RAASi during a single-blind, run-in phase of up to 12 weeks. After the run-in phase, patients were randomized to continue patiromer of withdraw patiromer during a double-blind treatment phase.

Results of the DIAMOND trial showed that treatment with the novel potassium binder patiromer results in lowering of serum potassium levels, which facilitate guideline-directed medical therapy in patients with HFrEF and CKD.

In a prespecified analysis of DIAMOND, the effect of patiromer was evaluated by subgroups of eGFR. A central laboratory assessed eGFR at baseline: below (n=414) or at and above (n=464) 60 mL/min/1.73 m² (category 1) or below (n=210) or at and ≥above (n=668) 45 mL/min/1.73m².

Main results

• In both categories, patiromer resulted in a significant mean change in serum potassium levels, with a larger improvement in those with lower eGFR levels (-0.07, 95%CI:-0.11 to -0.03 in group of ≥60 mL/min/1.73 m² vs. -0.14, 95%CI: -0.18 to -0.09 in group <60 mL/min/1.73 m², Pinteraction 0.027; -0.08, 95%CI:-0.11 to -0.04 in group of ≥45 mL/min/1.73 m² vs. -0.19, 95%CI:-0.28 to -0.12, Pinteraction=0.003).
• Time to first event of hyperkalemia was reduced in those with patiromer in all subgroups of eGFR, with no significant interactions.
• Patiromer prolonged time to reduction of MRA dose below target, regardless of eGFR subgroup.
• Win ratios for morbidity-adjusted hyperkalemia events were significantly higher with patiromer than placebo in all eGFR groups; win ration for RAASi use was higher with patiromer than placebo overall.
• Treatment emergent adverse events (TEAEs) leading to withdraw of the study medication occurred in 2.0-4.3% of patients across eGFR subgroups.
• Serious TEAEs occurred in 10.5-18.5% of patients across CKD subgroups. The highest percentage of serious TEAEs was in patients with eGFR < 45 mL/min/1.73 m² in the placebo arm.

Conclusions

Treatment with patiromer resulted in maintained lower levels of serum potassium than placebo in HFrEF patients across all CKD subgroups, with a greater effect size in patients with lower eGFR. Secondary endpoints of incidence of hyperkalemia events and proportion of patients maintained on MRA target doses were improved in those on patiromer compared to placebo across all CKD subgroups.

- Our reporting is based on the information provided at the ERA congress 2022 -

Read our summary of the DIAMOND trial Watch a video by prof. Butler on the DIAMOND trial