背景:肾功能障碍通常导致不愿开始或继续挽救生命的心力衰竭(HF)治疗。
目的:本研究旨在探讨盐皮质激素受体拮抗剂(MRAs)治疗射血分数降低并出现显著肾功能障碍的HF患者的疗效和安全性。
方法:我们汇集了RALES(随机醛内酯评估研究)和EMPHASIS-HF(依普利酮在轻度患者住院和心力衰竭生存研究中的应用)试验的个体患者数据。根据估计的肾小球滤过率(eGFR)是否下降至<30mL/min/1.73m2来评估MRA治疗与结果之间的关联。主要结果是心血管死亡或HF住院。
结果:在4,355名患者中,295(6.8%)在随机化至<30mL/min/1.73m2后经历eGFR恶化。这些患者的基线心脏和肾功能受损更多(eGFR47.3±13.4mL/min/1.73m2vs70.5±21.8mL/min/1.73m2),并且与没有eGFR恶化的患者相比,其主要结局的风险更高(HR:2.49;95%CI:2.01-3.08;P<0.001)。然而,在eGFR下降至<30mL/min/1.73m2(HR:0.65;95%CI:0.43~0.99)的患者中,与未进行MRA治疗的患者(HR:0.63;95%CI:0.56~0.71)(P交互作用=0.87)相比,使用MRA治疗的主要结局风险降低相似.在eGFR下降至<30mL/min/1.73m2的患者中,MRA治疗的主要结局减少了21例(每100人年)。与安慰剂相比,与超过3例严重高钾血症(>6.0mmol/L)的患者相比。
结论:由于eGFR降低至<30mL/min/1.73m2的患者处于非常高的风险,在这些患者中,MRA绝对风险降低幅度较大,且eGFR的这种下降不应自动导致治疗中止.
BACKGROUND: Kidney dysfunction often leads to reluctance to start or continue life-saving heart failure (HF) therapy.
OBJECTIVE: This study sought to examine the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) in patients with HF with reduced ejection fraction experiencing significant kidney dysfunction.
METHODS: We pooled individual patient data from the RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trials. The association between MRA treatment and outcomes was assessed according to whether the estimated glomerular filtration rate (eGFR) declined to <30 mL/min/1.73 m2 or not. The primary outcome was cardiovascular death or HF hospitalization.
RESULTS: Among 4,355 patients included, 295 (6.8%) experienced a deterioration of eGFR after randomization to <30 mL/min/1.73 m2. These patients had more impaired baseline cardiac and kidney function (eGFR 47.3 ± 13.4 mL/min/1.73 m2 vs 70.5 ± 21.8 mL/min/1.73 m2) and had a higher risk of the primary outcome than patients without eGFR deterioration (HR: 2.49; 95% CI: 2.01-3.08; P < 0.001). However, the risk reduction in the primary outcome with MRA therapy was similar in those who experienced a decrease in eGFR to <30 mL/min/1.73 m2 (HR: 0.65; 95% CI: 0.43-0.99) compared with those who did not (HR: 0.63; 95% CI: 0.56-0.71) (Pinteraction = 0.87). In patients with a decrease in eGFR to <30 mL/min/1.73 m2, 21 fewer individuals (per 100 person-years) experienced the primary outcome with MRA treatment, vs placebo, compared with an excess of 3 more patients with severe hyperkalemia (>6.0 mmol/L).
CONCLUSIONS: Because patients experiencing a decrease in eGFR to <30 mL/min/1.73 m2 are at very high risk, the absolute risk reduction with an MRA in these patients is large and this decline in eGFR should not automatically lead to treatment discontinuation.