在竞争风险荟萃分析中，卡维地洛可降低代偿期肝硬化患者

StephenW

在竞争风险荟萃分析中，卡维地洛可降低代偿期肝硬化患者的失代偿和死亡风险

    坦率的维拉纽瓦
    费兰·托雷斯
    希夫·库马尔·沙林
    埃迪尔玛·阿尔瓦拉多
    海梅·博世
    代表 Carvedilol-IPD-MA-group 和 Baveno Cooperation: an EASL Consortium
    显示所有作者

发布时间：2022年5月31日DOI：https://doi.org/10.1016/j.jhep.2022.05.021
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强调

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    卡维地洛可显着降低肝硬化和 CSPH 患者的失代偿风险，主要是通过降低腹水风险。
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    更重要的是，卡维地洛显着提高了代偿患者的生存率。
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    早期开始使用卡维地洛可以预防代偿期肝硬化和 CSPH 患者的疾病进展。
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    代偿期肝硬化患者应筛查CSPH，以便及早开始治疗。

背景与目标
非选择性β受体阻滞剂是否可以预防肝硬化失代偿需要澄清。卡维地洛可能特别有效，因为其内在的血管舒张活性可改善肝血管阻力，这是早期肝硬化门静脉高压症的主要机制。我们评估了卡维地洛是否可以预防代偿期肝硬化和有临床意义的门静脉高压症 (CSPH) 患者的失代偿和提高生存率。
方法
通过系统评价，我们确定了比较卡维地洛与对照治疗（无活性治疗或内镜下静脉曲张套扎 [EVL]）在既往无出血的肝硬化和 CSPH 患者中的随机对照试验 (RCT)。我们使用从 RCT 的主要研究人员获得的个体患者数据 (IPD) 进行了竞争风险事件发生时间的荟萃分析。仅包括代偿患者。主要结局是预防失代偿（肝移植和死亡是竞争事件）和死亡（肝移植是竞争事件）。使用基线协变量的倾向评分和治疗加权的逆概率 (IPTW) 方法调整模型。
结果
在评估的 125 项全文研究中，4 项 RCT 符合条件。 4 人提供 IPD 并被纳入，包括 352 名代偿期肝硬化患者、181 名接受卡维地洛治疗的患者和 171 名对照（79 名接受 EVL 和 92 名安慰剂）。各组之间的基线特征相似。 IPTW 的标准化差异小于 10%。卡维地洛发生肝硬化失代偿的风险低于对照组（亚分布风险比 [SHR] 0.506；95% CI 0.289-0.887；p = 0.017；I2 = 0.0%，Q-statistic-p = 0.880），主要是由于降低腹水风险（SHR 0.491；95% CI 0.247-0.974；p = 0.042；I2 = 0.0%，Q-statistic-p = 0.384）。卡维地洛的死亡风险也较低（SHR 0.417；95% CI 0.194-0.896；p = 0.025；I2 = 0.0%，Q-statistic-p = 0.989）。
结论
长期卡维地洛治疗减少了肝硬化的失代偿并显着提高了代偿期 CSPH 患者的生存率。这表明，对代偿期肝硬化患者进行 CSPH 筛查，以便及时开始使用卡维地洛，可以改善预后。
PROSPERO 注册号
CRD42019144786。
总结
从代偿期肝硬化到失代偿期肝硬化的转变与预期寿命显着降低有关。因此，预防代偿期肝硬化患者的失代偿将大大改善患者的预后。关于肝硬化和门静脉血压升高（门静脉高压）患者使用非选择性 β 受体阻滞剂（门静脉降压药物）一直存在争议。在此，我们使用竞争风险荟萃分析来优化样本量并正确研究肝硬化作为一种​​多状态疾病和结果作为时间依赖性事件，我们表明卡维地洛（一种非选择性β受体阻滞剂）与降低风险相关肝硬化和门静脉高压症患者的失代偿事件和提高生存率。

StephenW

Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis

    Càndid Villanueva
    Ferran Torres
    Shiv Kumar Sarin
    Edilmar Alvarado
    Jaume Bosch
    on behalf of theCarvedilol-IPD-MA-group and the Baveno Cooperation: an EASL Consortium
    Show all authors

Published:May 31, 2022DOI:https://doi.org/10.1016/j.jhep.2022.05.021
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Highlights

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    Carvedilol significantly decreases the risk of decompensation in patients with cirrhosis and CSPH, mainly by reducing risk of ascites.
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    Even more importantly, carvedilol significantly improves survival in compensated patients.
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    Early initiation of carvedilol could prevent disease progression in patients with compensated cirrhosis and CSPH.
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    Patients with compensated cirrhosis should be screened for CSPH, so that treatment can be started early.

Background & Aims
Whether non-selective β-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal hypertension in early cirrhosis. We assessed whether carvedilol may prevent decompensation and improve survival in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH).
Methods
By systematic review we identified randomized-controlled trials (RCTs) comparing carvedilol vs. control therapy (no-active treatment or endoscopic variceal ligation [EVL]) in patients with cirrhosis and CSPH without previous bleeding. We performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (liver transplantation and death were competing events) and death (liver transplantation was a competing event). Models were adjusted using propensity scores for baseline covariates with the inverse probability of treatment weighting (IPTW) approach.
Results
Among 125 full-text studies evaluated, 4 RCTs were eligible. The 4 provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo). Baseline characteristics were similar between groups. Standardized differences were <10% by IPTW. The risk of developing decompensation of cirrhosis was lower with carvedilol than in controls (subdistribution hazard ratio [SHR] 0.506; 95% CI 0.289-0.887; p = 0.017; I2 = 0.0%, Q-statistic-p = 0.880), mainly due to a reduced risk of ascites (SHR 0.491; 95% CI 0.247-0.974; p = 0.042; I2 = 0.0%, Q-statistic-p = 0.384). The risk of death was also lower with carvedilol (SHR 0.417; 95% CI 0.194-0.896; p = 0.025; I2 = 0.0%, Q-statistic-p = 0.989).
Conclusions
Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH. This suggests that screening patients with compensated cirrhosis for CSPH to enable the prompt initiation of carvedilol could improve outcomes.
PROSPERO registration number
CRD42019144786.
Lay summary
The transition from compensated cirrhosis to decompensated cirrhosis is associated with markedly reduced life expectancy. Therefore, preventing decompensation in patients with compensated cirrhosis would be associated with greatly improved patient outcomes. There has been controversy regarding the use of non-selective β-blockers (portal pressure-lowering medications) in patients with cirrhosis and elevated portal blood pressure (portal hypertension). Herein, using a competing-risk meta-analysis to optimize sample size and properly investigate cirrhosis as a multistate disease and outcomes as time-dependent events, we show that carvedilol (a non-selective β-blocker) is associated with a reduced risk of decompensating events and improved survival in patients with cirrhosis and portal hypertension.