Tapper Elliot B, Zhao Zhe, Winder G Scott, Parikh Neehar D
Division of Gastroenterology and Hepatology, University of Michigan, MI, United States.
JHEP Rep. 2022 Mar 25;4(6):100478. doi: 10.1016/j.jhepr.2022.100478. eCollection 2022 Jun.
BACKGROUND & AIMS: Benzodiazepines are associated with an increased risk of harm in patients with cirrhosis. However, stopping benzodiazepines must be done with care to avoid withdrawal or other unintended consequences. The impact of deprescribing on patients with cirrhosis is unknown.
We emulated a hypothetical 3-year trial of benzodiazepine deprescription among Medicare enrollees with compensated cirrhosis who lacked other life-limiting diagnoses. All received continuous benzodiazepine prescriptions for the 6-months prior to their diagnosis of cirrhosis. During a 90-day landmark period following their diagnosis of cirrhosis, patients were classified as complete deprescribers (no benzodiazepines dispensed), continuous users, or partial deprescribers. We used inverse probability treatment weighting to compare complete deprescribers to continuous users of traditional benzodiazepines and zolpidem. Outcomes accounted for competing risk of mortality and included incident decompensation (hepatic encephalopathy, ascites, or variceal bleeding), fractures, falls, and alcohol-related hospitalizations.
There were 1,651 and 1,463 continuous users of traditional benzodiazepines and zolpidem, respectively, and 728 complete deprescribers. Patients were aged a median of 68 years, 24% had alcohol-related cirrhosis. There was no difference in the risk of death or decompensation for continuous users and deprescribers. Among deprescribers of traditional benzodiazepines, there was no improvement in the risk of falls or fractures. However, compared to continuous zolpidem users, deprescribers had a lower risk of falls (23.2% 31%, = 0.04) and fractures (21% 29%, = 0.02).
Deprescribing zolpidem reduces the risk of falls and fractures. However, deprescribing benzodiazepines does not improve the risk of decompensation. Efforts to safely address the indications for benzodiazepines such as insomnia and anxiety are urgently needed.
Many people with cirrhosis have anxiety, depression, and sleep disorders. Increasingly, patients with cirrhosis are treated with sedating medications called benzodiazepines, including valium, alprazolam ('Xanax'), clonopin, and the sleep-aid zolpidem ('Ambien'), which can cause falls, broken bones, and maybe other brain disorders. For this reason, many researchers are interested in trials of 'deprescribing' (stopping) benzodiazepines. However, no trials have been performed. We used health record data to simulate a trial of deprescribing. We found that stopping benzodiazepines may reduce the chance of falls or broken bones, but it does not improve survival or liver health.
苯二氮䓬类药物与肝硬化患者伤害风险增加相关。然而，停用苯二氮䓬类药物必须谨慎进行，以避免戒断反应或其他意外后果。减药对肝硬化患者的影响尚不清楚。
我们模拟了一项针对患有代偿期肝硬化且无其他危及生命诊断的医疗保险参保者进行的为期3年的苯二氮䓬类药物减药假设试验。所有患者在被诊断为肝硬化前的6个月内均持续接受苯二氮䓬类药物处方。在诊断为肝硬化后的90天标志性时期内，患者被分类为完全停药者（未配发苯二氮䓬类药物）、持续使用者或部分停药者。我们使用逆概率治疗加权法将完全停药者与传统苯二氮䓬类药物和唑吡坦的持续使用者进行比较。结局考虑了死亡的竞争风险，包括新发失代偿（肝性脑病、腹水或静脉曲张出血）、骨折、跌倒和酒精相关住院。
分别有1651名和1463名传统苯二氮䓬类药物和唑吡坦的持续使用者，以及728名完全停药者。患者年龄中位数为68岁，24%患有酒精性肝硬化。持续使用者和停药者在死亡或失代偿风险方面没有差异。在传统苯二氮䓬类药物停药者中，跌倒或骨折风险没有改善。然而，与唑吡坦持续使用者相比，停药者跌倒风险较低（23.2%对31%，P = 0.04），骨折风险较低（21%对29%，P = 0.02）。
停用唑吡坦可降低跌倒和骨折风险。然而，停用苯二氮䓬类药物并不能改善失代偿风险。迫切需要努力安全解决苯二氮䓬类药物的适应证，如失眠和焦虑。
许多肝硬化患者有焦虑、抑郁和睡眠障碍。越来越多的肝硬化患者接受称为苯二氮䓬类药物的镇静药物治疗，包括安定、阿普唑仑（“赞安诺”）、氯硝西泮，以及助眠药物唑吡坦（“安必恩”），这些药物可导致跌倒、骨折，可能还会引发其他脑部疾病。因此，许多研究人员对“减药”（停用）苯二氮䓬类药物的试验感兴趣。然而，尚未进行过试验。我们使用健康记录数据模拟了减药试验。我们发现停用苯二氮䓬类药物可能会降低跌倒或骨折的几率，但并不能改善生存率或肝脏健康状况。
