Pravastatin reduces all-cause mortality in elderly individuals at risk of liver fibrosis: Post hoc analysis of the PROSPER trial

IF 9.5 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Vivian de Jong , Willy Theel , Manuel Castro Cabezas , Diederick E. Grobbee , Wouter Jukema , Stella Trompet
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引用次数: 0

Abstract

Background & Aims

Metabolic dysfunction-associated steatotic liver disease (MASLD), especially the progressive stages accompanied by liver fibrosis, are associated with liver-related and cardiovascular (CV) complications in middle-aged cohorts. We evaluated whether liver fibrosis is associated with increased mortality and cause-specific endpoints in an elderly population, and whether statin treatment could reduce these risks.

Methods

PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) was a double-blind randomized clinical trial comparing pravastatin to placebo in an elderly Caucasian population of 5,804 patients (>70 years of age) at increased risk of CV disease. Endpoints were composite and single (CV) endpoints and all-cause mortality. The Fibrosis-4 index (FIB-4) score was classified as: low risk of liver fibrosis (FIB-4 <2.0), indeterminate risk (2.0≤ FIB-4 ≤2.66), and high risk (FIB-4 ≥2.67). Time-to-event data were analyzed using the Cox proportional hazards model.

Results

Most participants were classified in the low FIB-4 class (n = 3,919), followed by the indeterminate (n = 1,269) and high classes (n = 561). In the placebo group, the risk of all-cause mortality increased with a high FIB-4 classification: high-class hazard ratio (HR) = 1.54 (95% CI, 1.10–2.17), compared with the low class (reference group). In the pravastatin group, the HR for all-cause mortality was not associated with FIB-4 classification: high-class HR = 1.01 (95% CI, 0.69–1.49). The interaction between FIB-4 class and treatment was significant (p = 0.049). High FIB-4 classifications were not significantly associated with major adverse cardiovascular events (MACE) or other endpoints in either arms.

Conclusions

A high FIB-4 classification is associated with increased all-cause mortality in the elderly, although pravastatin appears to mitigate this increased risk.

Clinical Trials registration

The study is registered at www.isrctn.com/(ISRCTN40976937).

Impact and implications

The progressive stages of MASLD (liver fibrosis) are associated with liver-related and CV complications in middle-aged cohorts (∼55 years of age). The impact of liver fibrosis in elderly populations is less well studied. In addition, the use of statins has long been debated, but evidence appears to point to a beneficial effect in populations with MASLD. However, data from prospective trials remain limited. Our findings indicate a potential survival benefit associated with pravastatin use in the elderly (>70 years of age) with an indication of liver fibrosis.

Abstract Image

普伐他汀降低有肝纤维化风险的老年人的全因死亡率:PROSPER试验的事后分析
背景,目的:在中年人群中,代谢功能障碍相关的脂肪变性肝病(MASLD),尤其是伴有肝纤维化的进行性阶段,与肝脏相关和心血管(CV)并发症相关。我们评估了肝纤维化是否与老年人群死亡率和病因特异性终点增加有关,以及他汀类药物治疗是否可以降低这些风险。方法普伐他汀在高危老年人中的前瞻性研究(PROSPER)是一项双盲随机临床试验,在5804例心血管疾病风险增加的老年高加索人群(70岁)中比较普伐他汀和安慰剂。终点为复合终点、单终点和全因死亡率。纤维化-4指数(FIB-4)评分分为:低危(FIB-4 <2.0)、不确定(2.0≤FIB-4≤2.66)、高危(FIB-4≥2.67)。使用Cox比例风险模型对事件时间数据进行分析。结果大多数受试者属于FIB-4低级别(n = 3919),其次是不确定级别(n = 1269)和高级别(n = 561)。在安慰剂组中,高FIB-4分类的全因死亡风险增加:与低类别(参照组)相比,高类别风险比(HR) = 1.54 (95% CI, 1.10-2.17)。在普伐他汀组,全因死亡率的HR与FIB-4分类无关:高级别HR = 1.01 (95% CI, 0.69-1.49)。FIB-4分级与治疗的交互作用显著(p = 0.049)。在两组中,高FIB-4分类与主要不良心血管事件(MACE)或其他终点无显著相关性。结论:高FIB-4分级与老年人全因死亡率增加有关,尽管普伐他汀似乎可以减轻这种增加的风险。临床试验注册:该研究注册于www.isrctn.com/(ISRCTN40976937).Impact及其意义在中年队列(~ 55岁)中,进展阶段的MASLD(肝纤维化)与肝脏相关和CV并发症相关。肝纤维化对老年人群的影响研究较少。此外,他汀类药物的使用一直存在争议,但有证据表明他汀类药物对MASLD患者有益。然而,来自前瞻性试验的数据仍然有限。我们的研究结果表明,在有肝纤维化指征的老年人(70岁)中使用普伐他汀有潜在的生存益处。
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来源期刊
JHEP Reports
JHEP Reports GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
12.40
自引率
2.40%
发文量
161
审稿时长
36 days
期刊介绍: JHEP Reports is an open access journal that is affiliated with the European Association for the Study of the Liver (EASL). It serves as a companion journal to the highly respected Journal of Hepatology. The primary objective of JHEP Reports is to publish original papers and reviews that contribute to the advancement of knowledge in the field of liver diseases. The journal covers a wide range of topics, including basic, translational, and clinical research. It also focuses on global issues in hepatology, with particular emphasis on areas such as clinical trials, novel diagnostics, precision medicine and therapeutics, cancer research, cellular and molecular studies, artificial intelligence, microbiome research, epidemiology, and cutting-edge technologies. In summary, JHEP Reports is dedicated to promoting scientific discoveries and innovations in liver diseases through the publication of high-quality research papers and reviews covering various aspects of hepatology.
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