Pollack Charles V, Arroyo David, Kanda Eiichiro, Lázaro Ignacio José Sánchez, Lesén Eva, Franzén Stefan, Gray Christen M, Lipińska Anna, Murohara Toyoaki, Rastogi Anjay
Department of Emergency Medicine, University of Mississippi School of Medicine, Jackson, Mississippi, USA.
Nephrology Department, Hospital General, Universitario Gregorio Marañón, Madrid, Spain.
ESC Heart Fail. 2025 Jun;12(3):1776-1785. doi: 10.1002/ehf2.15171. Epub 2024 Dec 10.
Renin-angiotensin-aldosterone system inhibitors (RAASi) are foundational in the management of heart failure (HF) and chronic kidney disease (CKD) but increase the risk of hyperkalaemia. To facilitate continuation of RAASi therapy, guidelines suggest managing hyperkalaemia using newer potassium binders such as sodium zirconium cyclosilicate (SZC). This observational study describes the likelihood of continued RAASi therapy by duration of SZC treatment.
The study population included non-dialysis-dependent adults diagnosed with HF and/or CKD who initiated outpatient SZC treatment while receiving RAASi therapy. Patients were identified using healthcare registers and claims data from the United States, Japan and Spain. SZC treatment duration was described using the Kaplan-Meier method. Hernán's clone-censor-weight (CCW) approach, using principles of trial emulation, was applied to evaluate the likelihood of continued RAASi therapy at specific time points by distinct SZC treatment durations, using a weighted Kaplan-Meier method and Z-tests.
The study included 7980 patients, from the United States (n = 4849), Japan (n = 2759) and Spain (n = 372). Across the three countries, mean patient age was 73.1-75.0 years, 53.2%-66.4% of patients were male, 39.0%-75.0% had HF and 76.9%-95.3% had CKD. Between Days 30 and 120, the percentage of patients remaining on SZC treatment decreased from 36.5% to 12.8% in the United States, from 63.8% to 33.7% in Japan, and from 81.9% to 65.0% in Spain. In the United States, patients who continued SZC treatment beyond 30 days had a higher likelihood of continuing RAASi therapy for up to 90 days (P < 0.001), and continuing SZC treatment beyond 60 days was superior for continuing RAASi therapy for up to 6 months (P < 0.001), versus earlier SZC discontinuation. At 120 days, the likelihood of remaining on RAASi therapy was 69%-70% for SZC treatment durations exceeding 60 days, versus 59% for shorter durations (1-30 days) (P < 0.001). Similar patterns were observed in Japan. At 120 days, the likelihood of remaining on RAASi therapy was 86%-87% for SZC treatment durations exceeding 90 days, versus 82% for shorter SZC treatment durations (1-30 days) (P < 0.05). The CCW analyses were not deemed feasible in the Spanish dataset due to the smaller initial sample size and few patients having a relatively short SZC treatment duration.
Patients with longer SZC treatment experience sustained protection against RAASi discontinuation, and the risk of RAASi discontinuation resumes once SZC is discontinued.
肾素-血管紧张素-醛固酮系统抑制剂（RAASi）是心力衰竭（HF）和慢性肾脏病（CKD）管理的基础，但会增加高钾血症风险。为便于继续使用RAASi治疗，指南建议使用新型钾结合剂如环硅酸锆钠（SZC）来处理高钾血症。这项观察性研究描述了根据SZC治疗持续时间继续使用RAASi治疗的可能性。
研究人群包括诊断为HF和/或CKD且在接受RAASi治疗时开始门诊SZC治疗的非透析依赖型成年人。利用美国、日本和西班牙的医疗保健登记册和索赔数据识别患者。使用Kaplan-Meier方法描述SZC治疗持续时间。应用Hernán的克隆审查权重（CCW）方法，采用试验模拟原则，通过加权Kaplan-Meier方法和Z检验，评估在特定时间点不同SZC治疗持续时间下继续使用RAASi治疗的可能性。
该研究纳入了7980例患者，来自美国（n = 4849）、日本（n = 2759）和西班牙（n = 372）。在这三个国家中，患者平均年龄为73.1 - 75.0岁，53.2% - 66.4%为男性，39.0% - 75.0%患有HF，76.9% - 95.3%患有CKD。在第30天至120天之间，美国继续接受SZC治疗的患者百分比从36.5%降至12.8%，日本从63.8%降至33.7%，西班牙从81.9%降至65.0%。在美国，持续接受SZC治疗超过30天的患者在长达90天内继续使用RAASi治疗的可能性更高（P < 0.001），持续接受SZC治疗超过60天在长达6个月内继续使用RAASi治疗方面优于更早停用SZC（P < 0.001）。在第120天，SZC治疗持续时间超过60天的患者继续使用RAASi治疗的可能性为69% - 70%，而持续时间较短（1 - 30天）的为59%（P < 0.001）。在日本观察到类似模式。在第120天，SZC治疗持续时间超过90天的患者继续使用RAASi治疗的可能性为86% - 87%，而SZC治疗持续时间较短（1 - 30天）的为82%（P < 0.05）。由于初始样本量较小且接受SZC治疗持续时间相对较短的患者较少，CCW分析在西班牙数据集中被认为不可行。
接受SZC治疗时间较长的患者在防止停用RAASi方面具有持续的保护作用，一旦停用SZC，停用RAASi的风险就会恢复。
