Fortea Jose Ignacio, Alvarado-Tapias Edilmar, Simbrunner Benedikt, Ezcurra Iranzu, Hernández-Gea Virginia, Aracil Carles, Llop Elba, Puente Angela, Roig Cristina, Reiberger Thomas, García-Pagan Juan Carlos, Calleja José Luis, Ferrero-Gregori Andreu, Mandorfer Matthias, Villanueva Candid, Crespo Javier
Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital, Santander, Spain.
Department of Gastroenterology, Hospital Santa Creu i Sant Pau, Barcelona, Spain. Universitat Autònoma de Barcelona (UAB), Departament de Medicina UAB, Barcelona, Spain; Centre for Biomedical Research in Liver and Digestive Diseases Network (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
J Hepatol. 2024 Dec 17. doi: 10.1016/j.jhep.2024.12.017.
BACKGROUND & AIMS: Data on the effectiveness of classical non-selective beta-blockers (cNSBBs, i.e., propranolol and nadolol) vs. carvedilol in patients with cirrhosis are scarce. In the present study, we aimed to compare their potential for preventing decompensation and mortality in patients with compensated and decompensated cirrhosis.
We performed a multicenter retrospective study including patients with compensated and decompensated cirrhosis with clinically significant portal hypertension, undergoing measurement of hepatic venous pressure gradient (HVPG) to assess acute hemodynamic response to intravenous propranolol (i.e., HVPG decrease ≥10% from baseline value) prior to primary prophylaxis for variceal bleeding. Outcomes were adjusted using inverse probability of treatment weighting in a competitive risk framework.
A total of 540 patients were included, 256 with compensated (cNSBBs n = 111; carvedilol n = 145) and 284 with decompensated (cNSBBs n = 134; carvedilol n = 150) cirrhosis. Median follow-up was 36.3 (IQR 16.9-61.0) and 30.7 (IQR 13.1-52.2) months, respectively. After covariate balancing, compared to cNSBBs, carvedilol significantly reduced the risk of a first decompensation in compensated patients (subdistribution hazard ratio 0.61; 95% CI 0.41-0.92; p = 0.019) and a combined endpoint of further decompensation/death in decompensated patients (subdistribution hazard ratio 0.57; 95% CI 0.42-0.77; p <0.0001). A second HVPG was conducted on 176 (68.8%, compensated) and 177 (62.3%, decompensated) patients. Acute non-responders, both compensated (11.1% vs. 29.4%; p = 0.422) and decompensated (16.0% vs. 43.6%: p = 0.0247) patients, showed a higher likelihood of achieving a chronic hemodynamic response with carvedilol. The safety profile of each type of NSBB was comparable in both cohorts.
Our data endorse the current recommendation favoring the use of carvedilol for the prevention of a first decompensation of cirrhosis and suggest extending the recommendation to patients with decompensated cirrhosis without recurrent or refractory ascites.
This study addresses a gap in the comparative effectiveness of classical non-selective beta-blockers (e.g., propranolol and nadolol) vs. carvedilol in managing cirrhosis in both compensated and decompensated stages. Our results support the preferential use of carvedilol in both settings due to its superior efficacy in reducing first and further decompensation. However, owing to the retrospective nature of the study and inherent selection biases, we advise against broadly applying these findings to patients with decompensated cirrhosis who exhibit signs of circulatory dysfunction or recurrent/refractory ascites.
关于经典非选择性β受体阻滞剂（cNSBBs，即普萘洛尔和纳多洛尔）与卡维地洛在肝硬化患者中的疗效数据较少。在本研究中，我们旨在比较它们在代偿期和失代偿期肝硬化患者中预防失代偿和死亡的潜力。
我们进行了一项多中心回顾性研究，纳入了有临床显著门静脉高压的代偿期和失代偿期肝硬化患者，在进行静脉曲张出血一级预防之前，测量肝静脉压力梯度（HVPG）以评估静脉注射普萘洛尔后的急性血流动力学反应（即HVPG较基线值降低≥10%）。在竞争风险框架下使用治疗权重的逆概率对结果进行调整。
共纳入540例患者，其中256例为代偿期（cNSBBs组111例；卡维地洛组145例），284例为失代偿期（cNSBBs组134例；卡维地洛组150例）肝硬化患者。中位随访时间分别为36.3（四分位间距16.9 - 61.0）个月和30.7（四分位间距13.1 - 52.2）个月。在协变量平衡后，与cNSBBs相比，卡维地洛显著降低了代偿期患者首次失代偿的风险（亚分布风险比0.61；95%置信区间0.41 - 0.92；p = 0.019）以及失代偿期患者进一步失代偿/死亡的联合终点风险（亚分布风险比0.57；95%置信区间0.42 - 0.77；p <0.0001）。176例（68.8%，代偿期）和177例（62.3%，失代偿期）患者进行了第二次HVPG测量。急性无反应者，无论是代偿期（11.1%对29.4%；p = 0.422）还是失代偿期（16.0%对43.6%：p = 0.0247）患者，使用卡维地洛实现慢性血流动力学反应的可能性更高。两种类型的NSBB在两个队列中的安全性概况相当。
我们的数据支持当前推荐使用卡维地洛预防肝硬化首次失代偿，并建议将该推荐扩展至无反复或难治性腹水的失代偿期肝硬化患者。
本研究填补了经典非选择性β受体阻滞剂（如普萘洛尔和纳多洛尔）与卡维地洛在代偿期和失代偿期肝硬化管理中的比较疗效方面的空白。我们的结果支持在两种情况下优先使用卡维地洛，因为它在减少首次和进一步失代偿方面具有更高的疗效。然而，由于研究的回顾性性质和固有的选择偏倚，我们建议不要将这些发现广泛应用于有循环功能障碍迹象或反复/难治性腹水的失代偿期肝硬化患者。
