Department of Medicine, Cardiovascular Center, University of Michigan, Ann Arbor, MI, USA.
Division of Nephrology, Department of Medicine, University of Rochester School of Medicine, Rochester, NY, USA.
ESC Heart Fail. 2018 Jun;5(3):257-266. doi: 10.1002/ehf2.12265. Epub 2018 Jan 25.
Hyperkalaemia risk precludes optimal renin-angiotensin-aldosterone system inhibitor use in patients with heart failure (HF), particularly those with chronic kidney disease (CKD). Patiromer is a sodium-free, non-absorbed potassium (K )-binding polymer approved for the treatment of hyperkalaemia. In PEARL-HF, patiromer 25.2 g (fixed dose) prevented hyperkalaemia in HF patients with or without CKD initiating spironolactone. The current study evaluated the effectiveness of a lower starting dose of patiromer (16.4 g/day) followed by individualized titration in preventing hyperkalaemia and hypokalaemia when initiating spironolactone.
This open-label 8-week study enrolled 63 patients with CKD, serum K 4.3-5.1 mEq/L, and chronic HF, who, based on investigator opinion, should receive spironolactone. Eligible patients started spironolactone 25 mg/day and patiromer 16.8 g/day (divided into two doses), with patiromer titrated to maintain serum K 4.0-5.1 mEq/L. Mean (standard deviation) serum K was 4.78 (0.51) mEq/L at baseline; weekly values were 4.48-4.70 mEq/L during treatment. Serum K of 3.5-5.5 mEq/L at the end of study treatment (primary endpoint) was achieved by 57 (90.5%) patients; 53 (84.1%) had serum K 4.0-5.1 mEq/L. One patient (1.6%) developed hypokalaemia, and two patients (3.2%) developed hypomagnesaemia. Spironolactone was increased to 50 mg/day in all patients; 43 (68%) patients required one or more patiromer dose titration. Adverse events (AEs) occurred in 36 (57.1%) patients, with a low rate of discontinuations [four (6.3%) patients]. The most common AE was mild to moderate abdominal discomfort [four (6.3%) patients].
In this open-label study, patiromer 16.8 g/day followed by individualized titration maintained serum K within the target range in the majority of patients with HF and CKD, all of whom were uptitrated to spironolactone 50 mg/day, patiromer was well tolerated, with a low incidence of hyperkalaemia, hypokalaemia, and hypomagnesaemia.
高钾血症风险使得心力衰竭（HF）患者无法充分使用肾素-血管紧张素-醛固酮系统抑制剂，尤其是那些合并慢性肾脏病（CKD）的患者。非钠依赖性、不被吸收的钾（K）结合聚合物帕替络尔可用于治疗高钾血症，已获得批准。在 PEARL-HF 研究中，固定剂量的帕替络尔 25.2g 可预防 HF 合并或不合并 CKD 患者起始螺内酯治疗时发生高钾血症。本研究评估了起始剂量较低（16.4g/天）、随后个体化滴定的帕替络尔在 HF 合并 CKD 患者起始螺内酯治疗时预防高钾血症和低钾血症的有效性。
本开放标签、8 周研究纳入了 63 例 CKD（血清 K 4.3-5.1mEq/L）合并慢性 HF 患者，研究者认为这些患者应接受螺内酯治疗。符合条件的患者起始螺内酯 25mg/天和帕替络尔 16.8g/天（分为两次剂量），帕替络尔滴定至维持血清 K 4.0-5.1mEq/L。基线时的平均（标准差）血清 K 为 4.78（0.51）mEq/L；治疗期间每周的血清 K 值为 4.48-4.70mEq/L。研究治疗结束时（主要终点）57 例（90.5%）患者达到血清 K 3.5-5.5mEq/L；53 例（84.1%）患者的血清 K 4.0-5.1mEq/L。1 例（1.6%）患者发生低钾血症，2 例（3.2%）患者发生低镁血症。所有患者的螺内酯均增至 50mg/天；43 例（68%）患者需要进行一次或多次帕替络尔剂量滴定。36 例（57.1%）患者发生不良事件（AE），仅有 4 例（6.3%）患者停药。最常见的 AE 为轻度至中度腹部不适（4 例，6.3%）。
在这项开放标签研究中，起始剂量 16.8g/天的帕替络尔随后进行个体化滴定，使 HF 合并 CKD 患者的大多数患者的血清 K 维持在目标范围内，所有患者的螺内酯均增至 50mg/天，且均进行了帕替络尔滴定。帕替络尔耐受性良好，高钾血症、低钾血症和低镁血症发生率较低。
