Shukla Richa, Kramer Jennifer, Cao Yumei, Ying Jun, Tansel Aylin, Walder Annette, Advani Shailesh, El-Serag Hashem B, Kanwal Fasiha
Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
Am J Gastroenterol. 2016 Dec;111(12):1778-1787. doi: 10.1038/ajg.2016.440. Epub 2016 Sep 27.
Prior studies have demonstrated the efficacy of non-selective beta-blockers (NSBB) in preventing first variceal bleeding in patients with cirrhosis. However, little is known about the overall effectiveness of NSBB in routine clinical care.
We conducted a retrospective cohort study of cirrhotic patients without prior bleeding who initiated a NSBB (propranolol, nadolol) at any Veterans Administration facility between 2008 and 2013. The primary outcome was variceal bleeding within 12 months. We conducted Cox-proportional hazards analyses to identify demographic, clinical, and NSBB-related (type of NSBB, mean dose, dose change, and heart rate response) factors associated with variceal bleeding.
Of 5,775 patients, 678 (11.7%) developed variceal bleeding. Mean daily dose of NSBB was <40 mg in 58.8%, 18.1% had either upward or downward titration in NSBB dose, and 9.8% had hemodynamic response. Patients who were younger, with ascites, greater medical comorbidity, and higher MELD (Model for end-stage liver disease) scores had a higher risk of variceal bleeding. Patients on a higher daily dose (>60 vs. <40 mg, adjusted hazard ratio (HR) 0.64; 95% confidence interval (CI): 0.51-0.81), who had either upward or downward dose titration (adjusted HR 0.69; 95% CI: 0.52-0.90 and 0.64; 95% CI 0.45-0.90, respectively), and those who achieved hemodynamic response (adjusted HR 0.75; 95% CI=0.57-1.0) had lower risk.
Approximately 12% of patients bled while being on NSBB for primary prophylaxis. A higher NSBB dose and dose titration were protective; yet most patients did not have the NSBB dose titrated to the recommended levels. Our data highlight the need for careful monitoring of cirrhotic patients on NSBB.
既往研究已证实非选择性β受体阻滞剂（NSBB）在预防肝硬化患者首次静脉曲张出血方面的疗效。然而，关于NSBB在常规临床护理中的整体有效性知之甚少。
我们对2008年至2013年间在任何退伍军人管理局设施开始使用NSBB（普萘洛尔、纳多洛尔）的无既往出血史的肝硬化患者进行了一项回顾性队列研究。主要结局是12个月内发生静脉曲张出血。我们进行了Cox比例风险分析，以确定与静脉曲张出血相关的人口统计学、临床和NSBB相关（NSBB类型、平均剂量、剂量变化和心率反应）因素。
在5775例患者中，678例（11.7%）发生了静脉曲张出血。58.8%的患者NSBB平均日剂量<40mg，18.1%的患者NSBB剂量有上调或下调，9.8%的患者有血流动力学反应。年龄较小、有腹水、合并症较多且终末期肝病模型（MELD）评分较高的患者发生静脉曲张出血的风险较高。日剂量较高（>60mg vs.<40mg，调整后风险比（HR）0.64；95%置信区间（CI）：0.51-0.81）、有剂量上调或下调（调整后HR分别为0.69；95%CI：0.52-0.90和0.64；95%CI 0.45-0.90）以及有血流动力学反应的患者（调整后HR 0.75；95%CI=0.57-1.0）风险较低。
约12%的患者在接受NSBB一级预防时发生出血。较高的NSBB剂量和剂量滴定具有保护作用；但大多数患者的NSBB剂量未滴定至推荐水平。我们的数据强调了对接受NSBB治疗的肝硬化患者进行仔细监测的必要性。
