Effects of Hypercholesterolemia and Statin Exposure on Survival in a Large National Cohort of Patients With Cirrhosis
Effects of Hypercholesterolemia and Statin Exposure on Survival in a Large National Cohort of Patients With Cirrhosis
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DOI：
10.1053/j.gastro.2019.01.026
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发表时间：
2019-05-01
期刊：
影响因子：
29.4
通讯作者：
Taddei, Tamar H.
中科院分区：
文献类型：
--
作者：
Kaplan, David E.;Serper, Marina A.;Taddei, Tamar H.
背景和目的：尽管有数据支持他汀类药物的使用，但与肝毒性相关的担忧经常导致肝硬化患者停止或不开始3-羟基-3-甲基戊二酰辅酶A还原酶治疗。我们研究了高脂血症和他汀类药物暴露对死亡率、肝功能失代偿和肝细胞癌发展的独立影响。方法：我们对2008年1月1日至2016年6月30日在退伍军人健康管理局新诊断的肝硬化患者进行了一项回顾性队列研究。受试者被分为2个队列：21921名既往他汀类药物暴露的患者（现有使用者）和51,023名他汀类药物初始个体，其中8794名随后开始他汀类药物治疗（新起始者），44,269名未开始他汀类药物治疗（非起始者）。构建了具有逆概率加权的多变量Cox比例风险模型，以评估随时间更新的脂质谱和累积暴露于他汀类药物对生存和肝代偿的影响。他汀类药物初始新启动者与非启动者倾向匹配，模拟他汀类药物在肝硬化中的随机对照试验。结果：在未使用他汀的受试者中，基线总胆固醇每增加10mg /dL与死亡率降低3.6%相关。在现有服药者中，每年持续服用他汀类药物与死亡率的风险比为0.920（95%可信区间0.0.897-0.943）相关。在风险集匹配后，新起始者每年的他汀类药物暴露与死亡率的风险比为0.913（95%可信区间0.890-0.937）。结论：在一项新诊断为肝硬化的退伍军人的回顾性队列研究中，我们将高胆固醇血症与保存良好的肝功能和降低的死亡率联系起来。尽管如此，他汀类药物暴露的每累积年与child - turcote - pugh A级和B级肝硬化患者死亡率下降8.0%-8.7%相关。
BACKGROUND & AIMS: Concerns related to hepatotoxicity frequently lead to discontinuation or non-initiation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase therapy in patients with cirrhosis despite data supporting statin use. We investigated the independent effects of hyperlipidemia and statin exposure on mortality, hepatic decompensation, and hepatocellular carcinoma development in a large national cohort of patients with cirrhosis. METHODS: We performed a retrospective cohort study of patients with newly diagnosed cirrhosis from January 1, 2008 through June 30, 2016 in the Veterans Health Administration. Subjects were divided into 2 cohorts: 21,921 patients with prior statin exposure (existing users) and 51,023 statin-naive individuals, of whom 8794 subsequently initiated statin therapy (new initiators) and 44,269 did not (non-initiators). Multi-variable Cox proportional hazard models with inverse probability weighting were constructed to assess the effects of time-updating lipid profiles and cumulative exposure to statins on survival and hepatic decompensation. Statin-naive new initiators were propensity matched with non-initiators to simulate a randomized controlled trial of statin use in cirrhosis. RESULTS: In statin-naive subjects, every 10-mg/dL increase in baseline total cholesterol was associated with a 3.6% decrease in mortality. In existing users, each year of continued statin exposure was associated with a hazard ratio of 0.920 (95% confidence interval 0.0.897-0.943) for mortality. After risk-set matching, each year of statin exposure among new initiators was associated with a hazard ratio of 0.913 (95% confidence interval 0.890-0.937) for mortality. CONCLUSIONS: In a retrospective cohort study of veterans with a new diagnosis of cirrhosis, we associated hypercholesterolemia with well-preserved hepatic function and decreased mortality. Nonetheless, each cumulative year of statin exposure was associated with an independent 8.0%-8.7% decrease of mortality of patients with cirrhosis of Child-Turcotte-Pugh classes A and B.