Sobolewski Kristine A, Brophy Alison, Choi Seohyun Claudia, Opsha Yekaterina
Department of Pharmacy, Saint Barnabas Medical Center, Livingston, NJ.
Ernest Mario School of Pharmacy-Rutgers University, Livingston, NJ.
Crit Care Explor. 2021 Apr 2;3(4):e0356. doi: 10.1097/CCE.0000000000000356. eCollection 2021 Apr.
Andexanet alfa is the first approved antidote in the management of life-threatening bleeds in patients treated with Xa inhibitors. The ANNEXA-4 study was successful in reducing factor Xa levels during time of administration but lacked correlation to improved patient outcomes. Given its novel mechanism of action, U.S. boxed warning, cost of up to $58,000 per dose, and limited efficacy data compared with standard of care, hospitals are faced with a dilemma with its addition to formulary and process for ensuring optimized use. The objective of this study was to evaluate adherence to institution restriction criteria and the clinical outcomes of treatment for patients for whom andexanet alfa is requested.
Retrospective cohort study of andexanet alfa requests within a 12-month time period.
A 600-bed community teaching hospital.
Patients whom pharmacists received request for dispensing andexanet alfa.
None.
Quality outcomes reviewed compliance to restriction criteria. Clinical outcomes evaluated use of adjunctive blood products, ICU length of stay, hospital length of stay, and hospital mortality. Safety outcomes evaluated incidence of thrombotic events.Andexanet alfa was requested for 16 patients from November 2018 to November 2019. It was administered in nine patients, with compliance to restriction criteria of 66.6%, average ICU length of stay 5.6 days, hospital length of stay 8.6 days, hospital mortality in 44.4%, and thrombotic events in 33.3%. Orders were rejected in seven patients with compliance to restriction criteria of 100%, ICU length of stay 3.2 days, hospital length of stay 5.5 days, hospital mortality in 14%, and thrombotic events in 14%.
A greater rate of adverse effects and mortality was identified with the use of andexanet alfa compared with clinical trials. This is potentially due to its use in a more severely ill patient population and lack of adherence to restriction criteria.
安多昔单抗是首个被批准用于治疗使用Xa因子抑制剂的患者危及生命出血的解毒剂。ANNEXA - 4研究成功降低了给药期间的Xa因子水平，但与改善患者预后缺乏相关性。鉴于其独特的作用机制、美国黑框警告、每剂高达58,000美元的成本以及与标准治疗相比有限的疗效数据，医院在将其纳入处方集以及确保优化使用的流程上面临两难境地。本研究的目的是评估对机构限制标准的遵守情况以及对请求使用安多昔单抗的患者的治疗临床结果。
对12个月内安多昔单抗请求进行回顾性队列研究。
一家拥有600张床位的社区教学医院。
药剂师收到分发安多昔单抗请求的患者。
无。
质量结果审查对限制标准的遵守情况。临床结果评估辅助血液制品的使用、重症监护病房（ICU）住院时间、住院时间和医院死亡率。安全结果评估血栓事件的发生率。2018年11月至2019年11月期间有16名患者被请求使用安多昔单抗。其中9名患者接受了治疗，对限制标准的遵守率为66.6%，平均ICU住院时间为5.6天，住院时间为8.6天，医院死亡率为44.4%，血栓事件发生率为33.3%。7名患者的用药请求被拒绝，对限制标准的遵守率为100%，ICU住院时间为3.2天，住院时间为5.5天，医院死亡率为14%，血栓事件发生率为14%。
与临床试验相比，使用安多昔单抗时发现不良反应和死亡率更高。这可能是由于其在病情更严重的患者群体中使用以及对限制标准的遵守不足。
