较高剂量的预防性β受体阻滞剂可能减轻静脉曲张出血

StephenW

Higher dose of prophylactic beta-blockers may lessen variceal bleeding

Shukla R, et al. Am J Gastroenterol. 2016;doi:10.1038/ajg.2016.440.
October 12, 2016

   

Patients with cirrhosis who received a higher dose of nonselective beta-blockers or dose titration during primary prophylaxis were less likely to experience first variceal bleeding compared with patients on a lower dose, according to published findings.


“Nonselective beta blockers are effective in primary prophylaxis against variceal bleeding; however, in a large portion of patients these medications are not being used effectively to achieve this benefit,” Richa Shukla, MD, of the section of gastroenterology and hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, told Healio.com/Hepatology.

Shukla and colleagues, including Fasiha Kanwal, MD, MHSH, of Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, performed a retrospective cohort study looking at 5,775 patients with cirrhosis without prior variceal bleeding who began treatment with a nonselective beta-blocker; 92.8% received propranolol (n = 5,361) and 7.2% received nadolol (n = 414). All patients were enrolled at a Veterans administration facility between 2008 and 2013 and followed to monitor the occurrence of variceal bleeding within 12 months of primary prophylaxis.


“Prior studies have demonstrated the efficacy of nonselective beta-blockers in preventing first variceal bleeding in patients with cirrhosis. However, little is known about the overall effectiveness of [nonselective beta-blockers] in routine clinical care,” the researchers wrote.

The researchers found that 11.7% of patients (n = 678) developed variceal bleeding and patients who were younger, had ascites, greater medical comorbidity and higher MELD scores had increased risk for bleeding.

The average daily dose of beta-blocker was more than 60 mg in 18.5% of patients. Approximately 18% of all patients experienced a change in the daily dose from baseline during the follow-up study period (n = 1,044). Of those who experienced a change in dosage, 10.3% of the total had an upward titration and 7.8% of the total had decrease in daily dose. Patients with lower than average beta-blocker dose were more likely to bleed compared with higher dosed patients (64.5% received less than 40 mg per day vs. 58.1%; CI, 0.51– 0.81) and patients without any dose titration (86.3% vs. 81.1%). The risk of variceal bleeding was 36% lower in patients who received a 60 mg dose or higher.

Patients who achieved hemodynamic response (adjusted HR = 0.75; 95% CI, 0.57–1.0) also had lower risk for bleeding.

The researchers found several clinical and demographic patient factors related to a higher risk of variceal bleeding, which may help to identify special populations requiring close monitoring as well.

“Clinicians should carefully monitor patients on nonselective beta-blockers and be proactive about titrating these medications in order to meet recommended hemodynamic parameters,” Shukla said. “Certain populations identified in this manuscript (i.e. younger patients, those with greater medical comorbidities and those with decompensated cirrhosis) may require even more careful monitoring due to higher risk of bleeding.”

Disclosure: The researchers report no relevant financial disclosures.

StephenW

较高剂量的预防性β受体阻滞剂可能减轻静脉曲张出血

Shukla R，et al。 Am J Gastroenterol。 2016; doi：10.1038 / ajg.2016.440。
2016年10月12日

   

根据发表的研究结果，与低剂量的患者相比，接受更高剂量的非选择性β受体阻滞剂或初次预防的剂量滴定的肝硬化患者不太可能出现首次静脉曲张出血。


“非选择性β受体阻滞剂对于静脉曲张出血的初步预防是有效的;然而，在大部分患者中，这些药物没有被有效地利用以实现这种益处，“来自Baylor医学院和Michael E.DeBakey退伍军人事务医疗中心的休斯顿的胃肠病学和肝病学部门的Richa Shukla，告诉Healio.com/Hepatology。

Shukla及其同事，包括贝勒医学院的Fasiha Kanwal，MD，MHSH和Michael E. DeBakey退伍军人事务医疗中心进行了一项回顾性队列研究，研究了5,775例肝硬化患者，之前没有静脉曲张出血，开始用非选择性β-阻断剂92.8％接受普萘洛尔（n = 5,361），7.2％接受纳多洛尔（n = 414）。所有患者在2008年至2013年期间在退伍军人管理机构登记，随后在初步预防的12个月内监测静脉曲张出血的发生。


“以前的研究已经证明非选择性β-受体阻滞剂在预防肝硬化患者的第一次静脉曲张出血中的功效。然而，对于[非选择性β受体阻滞剂]在常规临床护理中的整体有效性了解甚少，“研究人员写道。

研究人员发现，11.7％的患者（n = 678）出现了静脉曲张出血，并且年龄更小，腹水，更大的医疗合并症和更高的MELD评分增加了出血风险。

在18.5％的患者中，β受体阻滞剂的平均日剂量超过60mg。大约18％的所有患者在随访研究期间（n = 1,044）经历来自基线的日剂量的变化。在经历剂量变化的患者中，总剂量的10.3％具有向上滴定，并且总剂量的7.8％具有每日剂量的降低。与较高剂量的患者相比，具有低于平均β受体阻滞剂剂量的患者更可能出血（64.5％接受小于40mg /天，而58.1％; CI，0.51-0.81）和没有任何剂量滴定的患者（86.3％ .81.1％）。在接受60mg剂量或更高剂量的患者中，静脉曲张出血的风险降低36％。

实现血液动力学反应的患者（调整的HR = 0.75; 95％CI，0.57-1.0）也具有较低的出血风险。

研究人员发现了几个临床和人口学因素相关的更高的静脉曲张出血的风险，这可能有助于确定需要密切监测的特殊人群。

Shukla说：“临床医生应该仔细监测非选择性β受体阻滞剂的患者，并主动对这些药物进行滴定，以满足推荐的血液动力学参数。 “本手稿中确定的某些人群（即年轻患者，具有更大的合并症的患者和具有失代偿性肝硬化的患者）可能需要更仔细的监测，因为出血的风险更高。

披露：研究人员报告无相关财务披露。