肾素-血管紧张素系统抑制与代偿性肝硬化相关肝事件和死亡率的关系。
Association of Renin-Angiotensin System Inhibition With Liver-Related Events and Mortality in Compensated Cirrhosis.
机构信息
Keck School of Medicine, University of Southern California, Los Angeles, California.
Department of Population Public Health Sciences, University of Southern California, Los Angeles, Los Angeles, California; Division of Gastroenterology and Liver Diseases, University of Southern California, Los Angeles, California.
出版信息
Clin Gastroenterol Hepatol. 2024 Feb;22(2):315-323.e17. doi: 10.1016/j.cgh.2023.07.009. Epub 2023 Jul 24.
BACKGROUND & AIMS: While renin-angiotensin system inhibition lowers the hepatic venous gradient, the effect on more clinically meaningful endpoints is less studied. We aimed to quantify the relationship between renin-angiotensin system inhibition and liver-related events (LREs) among adults with compensated cirrhosis.
METHODS
In this national cohort study using the Optum database, we quantified the association between angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) use and LREs (hepatocellular carcinoma, liver transplantation, ascites, hepatic encephalopathy, or variceal bleeding) among patients with cirrhosis between 2009 and 2019. Selective beta-blocker (SBB) users served as the comparator group. We used demographic and clinical features to calculate inverse-probability treatment weighting-weighted cumulative incidences, absolute risk differences, and Cox proportional hazard ratios.
RESULTS
Among 4214 adults with cirrhosis, 3155 were ACE inhibitor/ARB users and 1059 were SBB users. In inverse probability treatment weighting-weighted analyses, ACE inhibitor/ARB (vs SBB) users had lower 5-year cumulative incidence (30.6% [95% confidence interval (CI), 27.8% to 33.2%] vs 41.3% [95% CI, 34.0% to 47.7%]; absolute risk difference, -10.7% [95% CI, -18.1% to -3.6%]) and lower risk of LREs (adjusted hazard ratio [aHR], 0.69; 95% CI, 0.60 to 0.80). There was a dose-response relationship: compared with SBB use, ACE inhibitor/ARB prescriptions ≥1 defined daily dose (aHR, 0.65; 95% CI, 0.56 to 0.76) were associated with a greater risk reduction compared with <1 defined daily dose (aHR, 0.87; 95% CI, 0.71 to 1.07). Results were robust across sensitivity analyses such as comparing ACE inhibitor/ARB users with nonusers and as-treated analysis.
CONCLUSIONS
In this national cohort study, ACE inhibitor/ARB use was associated with significantly lower risk of LREs in patients with compensated cirrhosis. These results provide support for a randomized clinical trial to confirm clinical benefit.
背景与目的
虽然肾素-血管紧张素系统抑制作用可降低肝静脉梯度，但对更有临床意义的终点的影响研究较少。本研究旨在定量评估血管紧张素转换酶（ACE）抑制剂或血管紧张素受体阻滞剂（ARB）在代偿性肝硬化成人中与肝脏相关事件（LREs）之间的关系。
方法
本项全国性队列研究使用 Optum 数据库，在 2009 年至 2019 年期间，评估了 ACE 抑制剂/ARB 使用者与肝硬化患者 LREs（肝细胞癌、肝移植、腹水、肝性脑病或静脉曲张出血）之间的关系。选择性β受体阻滞剂（SBB）使用者作为对照组。使用人口统计学和临床特征计算逆概率治疗权重加权累积发生率、绝对风险差异和 Cox 比例风险比。
结果
在 4214 例肝硬化成人中，3155 例为 ACE 抑制剂/ARB 使用者，1059 例为 SBB 使用者。在逆概率治疗权重加权分析中，ACE 抑制剂/ARB（与 SBB 相比）使用者的 5 年累积发生率较低（30.6%[95%置信区间（CI），27.8%至 33.2%] vs 41.3%[95% CI，34.0%至 47.7%]；绝对风险差异，-10.7%[95% CI，-18.1%至-3.6%]），LREs 风险较低（调整后的危险比[aHR]，0.69；95%CI，0.60 至 0.80）。存在剂量反应关系：与 SBB 相比，ACE 抑制剂/ARB 处方≥1 个定义日剂量（aHR，0.65；95%CI，0.56 至 0.76）与较低的风险降低相关，而<1 个定义日剂量（aHR，0.87；95%CI，0.71 至 1.07）。在比较 ACE 抑制剂/ARB 使用者与非使用者的敏感性分析以及治疗分析中，结果均具有稳健性。
结论
在这项全国性队列研究中，ACE 抑制剂/ARB 治疗与代偿性肝硬化患者 LREs 的风险显著降低相关。这些结果为随机临床试验证实临床获益提供了支持。
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