Supplementary Material for: 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

Introduction: Renin–angiotensin–aldosterone system inhibitor (RAASis; 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.
Methods: 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 m2 (added post hoc).
Results: In total, 81.3%, 78.9%, and 81.1% of patients with eGFR <60, <45, and <30 mL/min/1.73 m2 at screening achieved RAASi/MRA targets. A greater efficacy of patiromer vs placebo to control sK+ in patients with more advanced CKD was reported (p-interaction ≤ 0.027 for all eGFR subgroups). Greater effects on secondary endpoints were observed with patiromer vs placebo in patients with eGFR <60 and <45 mL/min/1.73 m2. Adverse effects were similar between patiromer and placebo across subgroups.
Conclusion: 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.

引言：肾素-血管紧张素-醛固酮系统抑制剂（Renin–angiotensin–aldosterone system inhibitor, RAASis；含盐皮质激素受体拮抗剂[mineralocorticoid receptor antagonists, MRAs]）对射血分数降低型心力衰竭（heart failure with reduced ejection fraction, HFrEF）合并慢性肾脏病（chronic kidney disease, CKD）患者的获益最为显著，但高钾血症（hyperkalemia, HK）发生风险较高。
方法：DIAMOND试验（临床试验注册号：NCT03888066）评估了帕替罗默（patiromer）对伴/不伴CKD的HFrEF患者血清钾（serum potassium, sK+）水平的调控能力。在1:1双盲撤药随机分组前，入组患者需在导入期内达到RAASis推荐剂量的≥50%，且盐皮质激素受体拮抗剂剂量为每日50mg，同时血钾处于正常范围。本分析针对预先设定的≥/＜60、≥/＜45 mL/min/1.73m²，以及事后新增的≥/＜30 mL/min/1.73m²亚组，评估了基线估算肾小球滤过率（estimated glomerular filtration rate, eGFR）的影响。
结果：筛查时估算肾小球滤过率＜60、＜45、＜30 mL/min/1.73m²的患者中，分别有81.3%、78.9%、81.1%达到了RAASi/MRA治疗目标剂量。相较于安慰剂，帕替罗默对肾功能更差的CKD患者的血清钾调控效果更显著（所有eGFR亚组的交互作用P值均≤0.027）。在估算肾小球滤过率＜60、＜45 mL/min/1.73m²的患者中，帕替罗默相较于安慰剂对次要终点的改善效果更明显。各亚组中，帕替罗默与安慰剂的不良反应发生率相似。
结论：帕替罗默可帮助HFrEF患者维持肾素-血管紧张素-醛固酮系统抑制剂治疗、调控血清钾水平，并降低高钾血症风险；在估算肾小球滤过率更低的患者亚组中，多数终点的效应量更为显著。所有eGFR亚组患者对帕替罗默的耐受性均良好。