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定量评估非选择性β受体阻滞剂在预防肝功能失代偿中的获益:PREDESCI 试验的贝叶斯再分析。

Quantifying the benefit of nonselective beta-blockers in the prevention of hepatic decompensation: A Bayesian reanalysis of the PREDESCI trial.

机构信息

Leeds Institute for Medical Research, University of Leeds, Leeds, UK.

Leeds Liver Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

出版信息

Hepatology. 2023 Aug 1;78(2):530-539. doi: 10.1097/HEP.0000000000000342. Epub 2023 Mar 13.

Abstract

BACKGROUND AND AIMS

Beta-blockers have been studied for the prevention of variceal bleeding and, more recently, for the prevention of all-cause decompensation. Some uncertainties regarding the benefit of beta-blockers for the prevention of decompensation remain. Bayesian analyses enhance the interpretation of trials. The purpose of this study was to provide clinically meaningful estimates of both the probability and magnitude of the benefit of beta-blocker treatment across a range of patient types.

APPROACH AND RESULTS

We undertook a Bayesian reanalysis of PREDESCI incorporating 3 priors (moderate neutral, moderate optimistic, and weak pessimistic). The probability of clinical benefit was assessed considering the prevention of all-cause decompensation. Microsimulation analyses were done to determine the magnitude of the benefit. In the Bayesian analysis, the probability that beta-blockers reduce all-cause decompensation was >0.93 for all priors. The Bayesian posterior hazard ratios (HR) for decompensation ranged from 0.50 (optimistic prior, 95% credible interval 0.27-0.93) to 0.70 (neutral prior, 95% credible interval 0.44-1.12). Exploring the benefit of treatment using microsimulation highlights substantial treatment benefits. For the neutral prior derived posterior HR and a 5% annual incidence of decompensation, at 10 years, an average of 497 decompensation-free years per 1000 patients were gained with treatment. In contrast, at 10 years 1639 years per 1000 patients were gained from the optimistic prior derived posterior HR and a 10% incidence of decompensation.

CONCLUSIONS

Beta-blocker treatment is associated with a high probability of clinical benefit. This likely translates to a substantial gain in decompensation-free life years at the population level.

摘要

背景和目的

β受体阻滞剂已被研究用于预防静脉曲张出血,最近也用于预防所有原因的失代偿。β受体阻滞剂预防失代偿的益处仍存在一些不确定性。贝叶斯分析增强了对试验的解释。本研究的目的是提供β受体阻滞剂治疗在一系列患者类型中的预防失代偿的获益的概率和幅度的临床有意义的估计。

方法和结果

我们对 PREDESCI 进行了贝叶斯重新分析,纳入了 3 个先验(中度中立、中度乐观和轻度悲观)。考虑预防所有原因的失代偿,评估了临床获益的概率。进行了微模拟分析以确定获益的幅度。在贝叶斯分析中,β受体阻滞剂降低所有原因的失代偿的概率对于所有先验都>0.93。贝叶斯后验失代偿风险比(HR)范围从 0.50(乐观先验,95%可信区间 0.27-0.93)到 0.70(中性先验,95%可信区间 0.44-1.12)。使用微模拟探索治疗的获益突出了治疗的实质性获益。对于中性先验衍生的后验 HR 和 5%的失代偿年发生率,在 10 年内,每 1000 名患者中有 497 年免于失代偿,治疗获益。相比之下,在 10 年内,每 1000 名患者中有 1639 年得益于乐观先验衍生的后验 HR 和 10%的失代偿年发生率。

结论

β受体阻滞剂治疗与高临床获益的概率相关。这可能在人群水平上转化为大量的免于失代偿的寿命增加。

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