Department of Cardiology, Tokyo Medical University, Tokyo, Japan.
Department of Nursing, Kiryu University, Gunma, Japan.
Int J Cardiol. 2024 Nov 15;415:132477. doi: 10.1016/j.ijcard.2024.132477. Epub 2024 Aug 22.
The guidelines recommend the initiation or up-titration of heart failure (HF) treatments following an HF hospitalization; however, concerns about adverse events may limit the use of mineralocorticoid receptor antagonists (MRAs). Patient profiles or disease severity might impact adverse events associated with MRA therapy in acute HF.
The EARLIER trial included patients with acute HF who were randomized to eplerenone or placebo over 6 months. Adverse events (i.e., worsening renal function [WRF], hyperkalemia, hypotension, and volume depletion/dehydration) were assessed. HF-related outcome included a composite of all-cause mortality, HF re-hospitalization, investigator-reported worsening HF and out-of-hospital diuretic intensification.
In 297 patients (mean age: 67 ± 13 years; 73% males), adverse events were observed: 44.4% experienced WRF (>20% drop in estimated glomerular filtration rate[eGFR] and/or investigator-reported WRF), 8.4% had hyperkalemia (potassium >5.5 mmol/L and/or investigator-reported hyperkalemia), 27.9% experienced hypotension (systolic blood pressure[SBP] <90 mmHg and/or investigator-reported hypotension), and 16.8% had investigator-reported volume depletion/dehydration. Eplerenone vs. placebo did not elevate the incidence of these events (all-p-values>0.0 5). Multivariable analyses revealed that, irrespective of treatment allocation, older age (>7 5 years), prevalent diabetes, symptomatic congestion, and microalbuminuria were associated with increased risk of WRF. Baseline eGFR<60 ml/min/1.73m and SBP < 90 mmHg predicted hyperkalemia and hypotension, respectively, while older patients were more likely to experience volume depletion/dehydration. However, these patient profiles did not alter the benefit of eplerenone on outcomes (HR [9 5%CI] = 0.53 [0.29 to 0.97], P = 0.04; all-p-for-interaction>0.10).
Eplerenone did not increase adverse events compared with placebo in acute HF. Importantly, disease severity and comorbidity burden greatly influence adverse events, but not benefit from eplerenone.
指南建议在心力衰竭（HF）住院后启动或增加心力衰竭治疗；然而，对不良反应的担忧可能会限制使用盐皮质激素受体拮抗剂（MRA）。患者特征或疾病严重程度可能会影响急性 HF 中与 MRA 治疗相关的不良反应。
EARLIER 试验纳入了 297 名急性 HF 患者，随机分为依普利酮或安慰剂治疗组，治疗时间为 6 个月。评估了不良反应（即肾功能恶化[WRF]、高钾血症、低血压和容量不足/脱水）。HF 相关结局包括全因死亡率、HF 再住院、研究者报告的 HF 恶化和院外利尿剂强化的复合终点。
在 297 名患者（平均年龄：67±13 岁；73%为男性）中观察到不良反应：44.4%发生 WRF（估计肾小球滤过率[eGFR]下降>20%和/或研究者报告的 WRF），8.4%发生高钾血症（血钾>5.5mmol/L 和/或研究者报告的高钾血症），27.9%发生低血压（收缩压[SBP]<90mmHg 和/或研究者报告的低血压），16.8%发生研究者报告的容量不足/脱水。依普利酮与安慰剂相比，这些事件的发生率没有增加（所有 P 值均>0.05）。多变量分析显示，无论治疗分配如何，年龄较大（>75 岁）、合并糖尿病、有症状的充血和微量白蛋白尿与 WRF 风险增加相关。基线 eGFR<60ml/min/1.73m 和 SBP<90mmHg 分别预测高钾血症和低血压，而年龄较大的患者更可能发生容量不足/脱水。然而，这些患者特征并没有改变依普利酮对结局的获益（HR [95%CI] = 0.53 [0.29 至 0.97]，P = 0.04；所有 P 值交互作用>0.10）。
与安慰剂相比，依普利酮并未增加急性 HF 患者的不良反应。重要的是，疾病严重程度和合并症负担极大地影响不良反应，但不影响依普利酮的获益。
