评价聚合物钾结合剂 RLY5016 在慢性心力衰竭（PEARL-HF 试验）患者中进行的双盲、安慰剂对照研究中的疗效和安全性。
Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial.
机构信息
University of Michigan, Ann Arbor, MI, USA.
出版信息
Eur Heart J. 2011 Apr;32(7):820-8. doi: 10.1093/eurheartj/ehq502. Epub 2011 Jan 5.
AIMS
To evaluate efficacy and safety of RLY5016 (a non-absorbed, orally administered, potassium [K+]-binding polymer) on serum K+ levels in patients with chronic heart failure (HF) receiving standard therapy and spironolactone.
METHODS AND RESULTS
One hundred and five patients with HF and a history of hyperkalaemia resulting in discontinuation of a renin-angiotensin-aldosterone system inhibitor/blocker and/or beta-adrenergic blocking agent or chronic kidney disease (CKD) with an estimated glomerular filtration rate of <60 mL/min were randomized to double-blind treatment with 30 g/day RLY5016 or placebo for 4 weeks. Spironolactone, initiated at 25 mg/day, was increased to 50 mg/day on Day 15 if K+ was ≤5.1 mEq/L. Endpoints included the change from baseline in serum K+ at the end of treatment (primary); the proportion of patients with hyperkalaemia (K+ >5.5 mEq/L); and the proportion titrated to spironolactone 50 mg/day. Safety assessments included adverse events (AEs) and clinical laboratory tests. RLY5016 (n= 55) and placebo (n= 49) patients had similar baseline characteristics. At the end of treatment, compared with placebo, RLY5016 had significantly lowered serum K+ levels with a difference between groups of -0.45 mEq/L (P < 0.001); a lower incidence of hyperkalaemia (7.3% RLY5016 vs. 24.5% placebo, P= 0.015); and a higher proportion of patients on spironolactone 50 mg/day (91% RLY5016 vs. 74% placebo, P= 0.019). In patients with CKD (n= 66), the difference in K+ between groups was -0.52 mEq/L (P= 0.031), and the incidence of hyperkalaemia was 6.7% RLY5016 vs. 38.5% placebo (P= 0.041). Adverse events were mainly gastrointestinal, and mild or moderate in severity. Adverse events resulting in study withdrawal were similar (7% RLY5016, 6% placebo). There were no drug-related serious AEs. Hypokalaemia (K+ <3.5 mEq/L) occurred in 6% of RLY5016 patients vs. 0% of placebo patients (P= 0.094).
CONCLUSION
RLY5016 prevented hyperkalaemia and was relatively well tolerated in patients with HF receiving standard therapy and spironolactone (25-50 mg/day).
目的
评估 RLY5016（一种非吸收性、口服、结合钾[K+]的聚合物）在接受标准治疗和螺内酯的慢性心力衰竭（HF）患者中的疗效和安全性，以降低血清 K+水平。
方法和结果
105 名 HF 患者既往因高钾血症而停用肾素-血管紧张素-醛固酮系统抑制剂/阻滞剂和/或β肾上腺素能阻滞剂，或因慢性肾脏病（CKD）导致估算肾小球滤过率 <60 mL/min，被随机分为双盲治疗组，每天服用 30 g RLY5016 或安慰剂，持续 4 周。如果 K+≤5.1 mEq/L，则在第 15 天开始将螺内酯增加至 50 mg/天。主要终点为治疗结束时与基线相比血清 K+的变化（主要终点）；高钾血症（K+>5.5 mEq/L）患者的比例；以及滴定至螺内酯 50 mg/天的患者比例。安全性评估包括不良事件（AE）和临床实验室检查。RLY5016（n=55）和安慰剂（n=49）患者的基线特征相似。治疗结束时，与安慰剂相比，RLY5016 可显著降低血清 K+水平，两组间差值为-0.45 mEq/L（P<0.001）；高钾血症的发生率较低（7.3% RLY5016 比 24.5%安慰剂，P=0.015）；且使用螺内酯 50 mg/天的患者比例较高（91% RLY5016 比 74%安慰剂，P=0.019）。在 CKD 患者（n=66）中，两组间 K+的差异为-0.52 mEq/L（P=0.031），高钾血症的发生率为 6.7% RLY5016 比 38.5%安慰剂（P=0.041）。不良事件主要为胃肠道，严重程度为轻度或中度。因不良事件退出研究的患者比例相似（7% RLY5016，6%安慰剂）。无药物相关严重不良事件。RLY5016 组出现低血钾（K+<3.5 mEq/L）的患者比例为 6%，安慰剂组为 0%（P=0.094）。
结论
RLY5016 可预防 HF 患者因接受标准治疗和螺内酯（25-50 mg/天）治疗而发生高钾血症，且耐受性良好。
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