Aims To investigate the impact of patiromer on serum potassium level and its ability to enable specified target doses of renin-angiotensin-aldosterone system inhibitor (RAASi) use in patients with heart failure and reduced ejection fraction (HFrEF). Methods and results A total of 1642 patients with HFrEF and current or a history of RAASi-related hyperkalemia were screened and 1195 were enrolled in the run-in phase with patiromer and optimization of RAASi therapy (≥50% recommended dose of angiotensin-converting-enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, and 50 mg of mineralocorticoid receptor antagonist [MRA] spironolactone or eplerenone). Specified target doses of RAASi therapy were achieved in 878 (84.6%) patients; 439 were randomized to patiromer and 439 to placebo. All patients, physicians, and outcome assessors were blinded to treatment assignment. The primary endpoint was between-group difference in adjusted mean change in serum potassium. Five hierarchical secondary endpoints were assessed. At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13, 43) weeks, the adjusted mean change in potassium was +0.03 mmol/L in the patiromer group and +0.13 mmol/L in the placebo group (difference in adjusted mean change between patiromer and placebo: -0.10 [95% confidence interval, CI -0.13, -0.07] mmol/L, P<0.001). Risk of hyperkalemia >5.5 mmol/L (hazard ratio [HR] 0.63; 95% CI 0.45, 0.87; P=0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P=0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P<0.001) were lower with patiromer. Hyperkalemia-related morbidity-adjusted events (win ratio 1.53, P<0.001) and total RAASi use score (win ratio 1.25, P=0.048) favored the patiromer arm. Adverse events were similar between groups. Conclusion Concurrent use of patiromer and high-dose MRAs reduces the risk of recurrent hyperkalemia (ClinicalTrials.gov: NCT03888066).

中文翻译：

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Patiromer 治疗射血分数降低的心力衰竭患者的高钾血症：DIAMOND 试验

目的 研究 patiromer 对血清钾水平的影响及其在心力衰竭和射血分数降低 (HFrEF) 患者中启用指定目标剂量肾素-血管紧张素-醛固酮系统抑制剂 (RAASi) 的能力。方法和结果 共筛选了 1642 例 HFrEF 和当前或既往有 RAASi 相关高钾血症的患者，其中 1195 例进入了使用 Patiromer 和优化 RAASi 治疗（≥50% 血管紧张素转换-推荐剂量）的磨合期。酶抑制剂/血管紧张素受体阻滞剂/血管紧张素受体脑啡肽酶抑制剂，和 50 mg 盐皮质激素受体拮抗剂 [MRA] 螺内酯或依普利酮）。878 名 (84.6%) 患者达到了指定的 RAASi 治疗目标剂量；439 人被随机分配到 Patiromer，439 人被随机分配到安慰剂组。所有患者、医生、结果评估者对治疗分配不知情。主要终点是调整后的血清钾平均变化的组间差异。评估了五个分层次要终点。治疗结束时，中位（四分位距）随访时间为 27 (13, 43) 周，patiromer 组调整后的钾平均变化为 +0.03 mmol/L，Patiromer 组为 +0.13 mmol/L安慰剂组（patiromer 和安慰剂之间的调整平均变化差异：-0.10 [95% 置信区间，CI -0.13，-0.07] mmol/L，P<0.001）。高钾血症风险 >5.5 mmol/L（风险比 [HR] 0.63；95% CI 0.45, 0.87；P=0.006），减少 MRA 剂量（HR 0.62；95% CI 0.45, 0.87；P=0.006），以及调整后的高钾血症事件总数/100 人年（77.7 vs. 118.2；HR 0.66；95% CI 0.53, 0.81；P<0. 001) 与 Patiromer 相比较低。高钾血症相关的发病率调整事件（胜率 1.53，P<0.001）和总 RAASi 使用评分（胜率 1.25，P=0.048）有利于 Patiromer 组。各组之间的不良事件相似。结论同时使用patiromer和大剂量MRA可降低复发性高钾血症的风险（ClinicalTrials.gov：NCT03888066）。