Patiromer-Facilitated Renin-Angiotensin-Aldosterone System Inhibitor Utilization in Patients with Heart Failure with or without Comorbid Chronic Kidney Disease : Subgroup Analysis of DIAMOND Randomized Trial

Renin-angiotensin-aldosterone system inhibitor (RAASi; including mineralocorticoid receptor antagonists [MRAs]) benefits are greatest in patients with heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD); however, the risk of hyperkalemia (HK) is high. The DIAMOND trial (NCT03888066) assessed the ability of patiromer to control serum potassium (sK +) in patients with HFrEF with/without CKD. Prior to randomization (double-blind withdrawal, 1:1), patients on patiromer had to achieve ≥50% recommended doses of RAASi and 50 mg/day of MRA with normokalemia during a run-in period. The present analysis assessed the effect of baseline estimated glomerular filtration rate (eGFR) in subgroups of ≥/<60, ≥/<45 (prespecified), and ≥/<30 mL/min/1.73 m 2 (added post hoc). In total, 81.3, 78.9, and 81.1% of patients with eGFR <60, <45, and <30 mL/min/1.73 m 2 at screening achieved RAASi/MRA targets. A greater efficacy of patiromer versus placebo to control sK + in patients with more advanced CKD was reported (p - ≤ 0.027 for all eGFR subgroups). Greater effects on secondary endpoints were observed with patiromer versus placebo in patients with eGFR <60 and <45 mL/min/1.73 m 2. Adverse effects were similar between patiromer and placebo across subgroups. Patiromer enabled use of RAASi, controlled sK +, and minimized HK risk in patients with HFrEF, with greater effect sizes for most endpoints noted in patient subgroups with lower eGFR. Patiromer was well tolerated by patients in all eGFR subgroups. Patients with chronic kidney disease (CKD) can develop high potassium (hyperkalemia) levels in their blood that can lead to complications such as heart issues. Renin-angiotensin-aldosterone system inhibitors (RAASis) are used as treatment for heart failure and CKD, but can also cause hyperkalemia, so are underutilized and used at lower than optimal doses. Patiromer is a potassium binder which was investigated in the DIAMOND trial to identify if it could reduce hyperkalemia in patients receiving RAASis. Lower kidney function (eGFR) has been associated with a greater likelihood of stopping treatment with RAASis; therefore, this analysis assessed the effect of patiromer on patients with varying eGFR levels. Patiromer enabled use of effective RAASi doses, controlled the serum potassium levels and minimized hyperkalemia in patients with heart failure and CKD.