RATIONALE & OBJECTIVE Angiotensin-converting enzyme (ACE) inhibitors are beneficial in heart failure with reduced ejection fraction (HFrEF). We sought to describe longitudinal trends in estimated glomerular filtration rate (eGFR) in HFrEF and how ACE-inhibitor therapy influences these changes. STUDY DESIGN Post hoc analysis of trial data. SETTINGS & PARTICIPANTS Symptomatic (Treatment Trial, n=2,423) and asymptomatic (Prevention Trial, n=4,094) patients from the Studies of Left Ventricular Dysfunction (SOLVD). EXPOSURE Enalapril versus placebo. OUTCOMES Early and long-term eGFR slope (ie, within and after the first 6 weeks) and 4 kidney end points: (1) serum creatinine level increase by≥0.3mg/dL, (2)>30% eGFR decline, (3)>40% eGFR decline, and (4) incident eGFR<30mL/min/1.73m2. ANALYTICAL APPROACH Shared parameter models, multivariable Cox regression models. RESULTS Baseline mean eGFR was lower in the Treatment Trial than in the Prevention Trial, 69.5±19.8 (SD) versus 76.2±18.6mL/min/1.73m2. Following randomization, an early eGFR decline occurred in the enalapril group; however, slopes during the median 3-year follow-up were not statistically different by randomization arm in either the Treatment Trial (-0.84 in enalapril vs-1.36mL/min/1.73m2 per year in placebo; P=0.08) or Prevention Trial (-1.27 in enalapril vs-1.36mL/min/1.73m2 per year in placebo; P=0.7). Random assignment to enalapril treatment increased the risk for all 4 outcomes in the Treatment Trial in the first 6-week period (HRs were 1.48 [95% CI, 1.10-1.99] for creatinine increase by≥0.3mg/dL; 1.38 [95% CI, 0.98-1.94] for eGFR decline> 30%; 2.60 [95% CI, 1.30-5.21] for eGFR decline> 40%; and 4.71 [95% CI, 1.78-12.50] for eGFR<30mL/min/1.73m2), but after the first year was not significantly associated with increased risk. A similar albeit less pronounced pattern was observed in the Prevention Trial, with risks present only in the early period. LIMITATIONS Creatinine results were not blinded, making it possible that ACE-inhibitor/placebo dosing was influenced by creatinine level. CONCLUSION Kidney function decline is slow in HFrEF. Although random assignment to enalapril treatment results in a statistically increased risk for kidney surrogates, the risk is limited to the early phase and late eGFR slopes and risks are not different by randomly assigned group.

中文翻译：

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射血分数降低的心力衰竭患者接受RAAS抑制后肾脏功能的变化趋势。

理由和目的血管紧张素转换酶（ACE）抑制剂可降低射血分数（HFrEF），对心力衰竭有益。我们试图描述HFrEF中估计的肾小球滤过率（eGFR）的纵向趋势，以及ACE抑制剂疗法如何影响这些变化。研究设计对试验数据进行事后分析。设置和参与者来自左心室功能不全研究（SOLVD）的有症状（治疗试验，n = 2,423）和无症状（预防试验，n = 4,094）患者。暴露与依那普利对比安慰剂。结果早期和长期eGFR斜率（即前6周之内和之后）和4个肾脏终点：（1）血清肌酐水平增加≥0.3mg/ dL，（2）eGFR下降> 30％，（3 ）> 40％的eGFR下降，和（4）入射的eGFR <30mL / min / 1.73m2。分析方法共享参数模型，多变量Cox回归模型。结果治疗试验中的基线平均eGFR低于预防试验中的69.5±19.8（SD）比76.2±18.6mL / min / 1.73m2。随机分组后，依那普利组eGFR较早下降。然而，无论是治疗试验（依那普利为-0.84 vs安慰剂为每年1.36mL / min / 1.73m2； P = 0.08），随机分组的中位3年随访期间的斜率在统计学上均无差异。 （依那普利为1.27，安慰剂组为1.36mL / min / 1.73m2 /年； P = 0.7）。随机分配依那普利治疗会增加前6周治疗试验中所有4个结局的风险（肌酐增加≥0.3mg/ dL时，HRs为1.48 [95％CI，1.10-1.99]； 1.38 [95％] eGFR下降> 30％的CI为0.98-1.94]； eGFR下降> 40％的为2.60 [95％CI，1.30-5.21]；和4。eGFR <30mL / min / 1.73m2为71 [95％CI，1.78-12.50]，但第一年后与增加的危险无明显关联。在预防试验中观察到了类似的虽然不太明显的模式，但风险只存在于早期。局限性肌酐水平并未盲目，因此ACE抑制剂/安慰剂的剂量可能会受到肌酐水平的影响。结论HFrEF的肾功能下降缓慢。尽管随机分配依那普利治疗会导致统计学上增加的肾脏替代物风险，但该风险仅限于早期和晚期eGFR斜率，并且随机分配组的风险无差异。在预防试验中观察到了类似的虽然不太明显的模式，但风险只存在于早期。局限性肌酐水平并未盲目，因此ACE抑制剂/安慰剂的剂量可能会受到肌酐水平的影响。结论HFrEF的肾功能下降缓慢。尽管随机分配依那普利治疗会导致统计学上增加的肾脏替代物风险，但该风险仅限于早期和晚期eGFR斜率，并且随机分配组的风险无差异。在预防试验中观察到了类似的虽然不太明显的模式，但风险只存在于早期。局限性肌酐水平并未盲目，因此ACE抑制剂/安慰剂的剂量可能会受到肌酐水平的影响。结论HFrEF的肾功能下降缓慢。尽管随机分配依那普利治疗会导致统计学上增加的肾脏替代物风险，但该风险仅限于早期和晚期eGFR斜率，并且随机分配组的风险无差异。