McGill University Health Centre, McGill University, Montreal, QC, Canada (B.R., A.S.).
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (S.J.G., M.F., J.-L.S., A.D.D, S.E.M., R.J.M., A.F.H., G.M.F.).
Circ Heart Fail. 2020 May;13(5):e006758. doi: 10.1161/CIRCHEARTFAILURE.119.006758. Epub 2020 May 4.
The FIGHT (Functional Impact of GLP-1 [glucagon-like peptide-1] for Heart Failure Treatment) trial randomized 300 patients with heart failure with reduced ejection fraction (HFrEF) and a recent hospitalization for heart failure to liraglutide versus placebo. While there was no difference in the primary outcome (rank score of time to death, time to rehospitalization for heart failure, and change in NT-proBNP [N-terminal pro-B-type natriuretic peptide]), there was a significant increase in cystatin C among patients randomized to liraglutide raising concern of adverse renal outcomes. We performed a post hoc analysis of FIGHT to investigate whether liraglutide was associated with worsening renal function (WRF).
The relationship between randomization to liraglutide and WRF was evaluated using logistic regression models. Two hundred seventy-four patients (91%) had complete data to assess for WRF defined as: increase in SCr ≥0.3 mg/dL, or ≥25% decrease in estimated glomerular filtration rate, or an increase in cystatin C ≥0.3 mg/L from baseline to 180-days.
Patients with WRF (n=113, 41%), compared with those without, were older, had more comorbidities, and lower utilization of guideline-directed medical treatment. Logistic regression models showed that age and baseline cystatin C levels were associated with WRF. In adjusted models, liraglutide was not associated with excess risk of WRF compared with placebo (odds ratio, 1.02 [95% CI, 0.62-1.67]). There was also no difference in the rank score when WRF was added as a fourth-tier outcome.
Liraglutide was not associated with WRF among patients with HFrEF and a recent hospitalization for heart failure. These data support the relative renal safety profile of liraglutide among patients with HFrEF. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01800968.
FIGHT（胰高血糖素样肽-1[GLP-1]对心力衰竭治疗的功能影响）试验将 300 名射血分数降低的心力衰竭（HFrEF）和近期心力衰竭住院的患者随机分为利拉鲁肽组和安慰剂组。虽然主要结局（死亡时间、心力衰竭再住院时间和 NT-proBNP[N 端 pro-B 型利钠肽]变化的秩评分）没有差异，但利拉鲁肽组患者的胱抑素 C 显著升高，这引起了人们对不良肾脏结局的担忧。我们对 FIGHT 进行了事后分析，以调查利拉鲁肽是否与肾功能恶化（WRF）有关。
使用逻辑回归模型评估随机分组至利拉鲁肽与 WRF 的关系。274 名患者（91%）有完整的数据来评估 WRF，定义为：血清肌酐（SCr）升高≥0.3mg/dL，或估算肾小球滤过率（eGFR）下降≥25%，或胱抑素 C 从基线增加≥0.3mg/L 至 180 天。
与无 WRF 相比，有 WRF 的患者（n=113，41%）年龄较大，合并症较多，指南指导的药物治疗使用率较低。逻辑回归模型显示，年龄和基线胱抑素 C 水平与 WRF 相关。在调整模型中，与安慰剂相比，利拉鲁肽与 WRF 风险增加无关（比值比，1.02[95%置信区间，0.62-1.67]）。将 WRF 作为第四层结局添加后，秩评分也没有差异。
在 HFrEF 和近期心力衰竭住院的患者中，利拉鲁肽与 WRF 无关。这些数据支持利拉鲁肽在 HFrEF 患者中的相对肾脏安全性。
