Angiotensin-converting enzyme inhibitors are beneficial in heart failure with reduced ejection fraction but are associated with acute declines in estimated glomerular filtration rate (eGFR). Prior studies evaluating thresholds of eGFR decline while using angiotensin-converting enzyme inhibitors in heart failure with reduced ejection have not taken into account this medication-driven decline. Here we used data from the Studies of Left Ventricular Dysfunction (SOLVD) trial of 6245 patients and performed Cox proportional hazards regression models to calculate hazard ratios of all-cause mortality and heart failure hospitalization-associated with percent eGFR decline at two- and six-weeks after randomization to enalapril versus placebo. In reference to placebo with equal degree of percent eGFR decline, any eGFR decline in the enalapril arm was associated with lower hazard of both outcomes. Under a conservative estimate using zero percent eGFR decline in the placebo arm as the reference, up to a 10% decline with enalapril was associated with mortality benefit (hazard ratio 0.87 [95% confidence interval 0.77, 0.99]) while up to a 35% decline was associated with decreased risk of heart failure hospitalization (0.78 [0.61, 0.98]). Under an intermediate estimate, up to a 15% decline with enalapril was associated with a mortality benefit (0.86 [0.77, 0.97]) and all levels of eGFR decline were associated with decreased risk of heart failure hospitalization. There was no percent eGFR decline, including up to 40%, in any models at either two- or six-weeks where enalapril was associated with higher mortality risk. Thus, in patients with reduced ejection fraction heart failure, enalapril is associated with decreased risk of mortality and heart failure hospitalizations. Hence, compelling reasons beyond moderate eGFR decline ought to be considered before its use is withdrawn.

血管紧张素转换酶抑制剂在心力衰竭中有益，其射血分数降低，但与估计的肾小球滤过率（eGFR）急剧下降有关。先前的研究评估了eGFR下降的阈值，而在心力衰竭且射血减少的情况下使用血管紧张素转化酶抑制剂时，并未考虑到这种药物驱动的下降。在这里，我们使用来自6245名患者的左心室功能不全研究（SOLVD）试验中的数据，并进行了Cox比例风险回归模型，以计算全因死亡率和心衰住院的风险比，以及在2和6岁时eGFR下降的百分比。依那普利与安慰剂随机分组后数周。对于eGFR下降百分比相等的安慰剂，依那普利组中任何eGFR下降均与两种预后的较低风险相关。根据安慰剂组的eGFR下降为零的保守估计，依那普利下降最多10％与死亡获益相关（危险比0.87 [95％置信区间0.77，0.99]），而最高可达35％下降与心力衰竭住院风险降低相关（0.78 [0.61，0.98]）。根据中间估计，依那普利最多可降低15％的死亡率（0.86 [0.77，0.97]），而eGFR的所有下降均与心衰住院风险的降低有关。在任何两周或六周内，依那普利与更高的死亡风险相关的模型中，eGFR均没有下降，包括高达40％。因此，在射血分数降低的心力衰竭患者中，依那普利与死亡率降低和心力衰竭住院相关。因此，在撤消其使用之前，应考虑超出eGFR适度下降的令人信服的原因。