Andexanet alpha versus four-factor prothrombin complex concentrate in DOACs anticoagulation reversal: an updated systematic review and meta-analysis.

IF 8.8 1区医学 Q1 CRITICAL CARE MEDICINE

Critical Care Pub Date : 2024-07-05 DOI:10.1186/s13054-024-05014-x

Daniele Orso, Federico Fonda, Alessandro Brussa, Irene Comisso, Elisabetta Auci, Marco Sartori, Tiziana Bove

{"title":"Andexanet alpha versus four-factor prothrombin complex concentrate in DOACs anticoagulation reversal: an updated systematic review and meta-analysis.","authors":"Daniele Orso, Federico Fonda, Alessandro Brussa, Irene Comisso, Elisabetta Auci, Marco Sartori, Tiziana Bove","doi":"10.1186/s13054-024-05014-x","DOIUrl":null,"url":null,"abstract":"Background: There is currently a lack of evidence for the comparative effectiveness of Andexanet alpha and four-factor prothrombin complex concentrate (4F-PCC) in anticoagulation reversal of direct oral anticoagulants (DOACs). The primary aim of our systematic review was to verify which drug is more effective in reducing short-term all-cause mortality. The secondary aim was to determine which of the two reverting strategies is less affected by thromboembolic events.Methods: A systematic review and meta-analysis was performed.Results: Twenty-two studies were analysed in the systematic review and quantitative synthesis. In all-cause short-term mortality, Andexanet alpha showed a risk ratio (RR) of 0.71(95% CI 0.37-1.34) in RCTs and PSMs, compared to 4F-PCC (I2 = 81%). Considering the retrospective studies, the pooled RR resulted in 0.84 (95% CI 0.69-1.01) for the common effects model and 0.82 (95% CI 0.63-1.07) for the random effects model (I2 = 34.2%). Regarding the incidence of thromboembolic events, for RCTs and PSMs, the common and the random effects model exhibited a RR of 1.74 (95% CI 1.09-2.77), and 1.71 (95% CI 1.01-2.89), respectively, for Andexanet alpha compared to 4F-PCC (I2 = 0%). Considering the retrospective studies, the pooled RR resulted in 1.21 (95% CI 0.87-1.69) for the common effects model and 1.18 (95% CI 0.86-1.62) for the random effects model (I2 = 0%).Conclusion: Considering a large group of both retrospective and controlled studies, Andexanet alpha did not show a statistically significant advantage over 4F-PCC in terms of mortality. In the analysis of the controlled studies alone, Andexanet alpha is associated with an increased risk of thromboembolic events.Clinical trial registration: PROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":null,"pages":null},"PeriodicalIF":8.8000,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225147/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Care","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13054-024-05014-x","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}

引用次数: 0

Abstract

Background: There is currently a lack of evidence for the comparative effectiveness of Andexanet alpha and four-factor prothrombin complex concentrate (4F-PCC) in anticoagulation reversal of direct oral anticoagulants (DOACs). The primary aim of our systematic review was to verify which drug is more effective in reducing short-term all-cause mortality. The secondary aim was to determine which of the two reverting strategies is less affected by thromboembolic events.

Methods: A systematic review and meta-analysis was performed.

Results: Twenty-two studies were analysed in the systematic review and quantitative synthesis. In all-cause short-term mortality, Andexanet alpha showed a risk ratio (RR) of 0.71(95% CI 0.37-1.34) in RCTs and PSMs, compared to 4F-PCC (I² = 81%). Considering the retrospective studies, the pooled RR resulted in 0.84 (95% CI 0.69-1.01) for the common effects model and 0.82 (95% CI 0.63-1.07) for the random effects model (I² = 34.2%). Regarding the incidence of thromboembolic events, for RCTs and PSMs, the common and the random effects model exhibited a RR of 1.74 (95% CI 1.09-2.77), and 1.71 (95% CI 1.01-2.89), respectively, for Andexanet alpha compared to 4F-PCC (I² = 0%). Considering the retrospective studies, the pooled RR resulted in 1.21 (95% CI 0.87-1.69) for the common effects model and 1.18 (95% CI 0.86-1.62) for the random effects model (I² = 0%).

Conclusion: Considering a large group of both retrospective and controlled studies, Andexanet alpha did not show a statistically significant advantage over 4F-PCC in terms of mortality. In the analysis of the controlled studies alone, Andexanet alpha is associated with an increased risk of thromboembolic events.

Clinical trial registration: PROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768.

查看原文本刊更多论文

在 DOACs 抗凝逆转中，ANDEXANET α 与凝血酶原四因子浓缩物的比较：最新系统综述和荟萃分析。

背景：目前缺乏证据表明安达沙尼α和四因子凝血酶原复合物浓缩物（4F-PCC）在直接口服抗凝药（DOACs）的抗凝逆转方面具有可比性。我们进行系统综述的主要目的是验证哪种药物在降低短期全因死亡率方面更有效。次要目的是确定两种逆转策略中哪一种受血栓栓塞事件的影响较小：方法：进行了系统回顾和荟萃分析：系统回顾和定量综合分析了22项研究。在全因短期死亡率方面，与 4F-PCC 相比，在 RCT 和 PSM 中，Andexanet alpha 的风险比 (RR) 为 0.71（95% CI 0.37-1.34）（I2 = 81%）。考虑到回顾性研究，共同效应模型的汇总 RR 为 0.84（95% CI 0.69-1.01），随机效应模型的汇总 RR 为 0.82（95% CI 0.63-1.07）（I2 = 34.2%）。关于血栓栓塞事件的发生率，在 RCT 和 PSM 中，与 4F-PCC 相比，共同效应和随机效应模型显示 Andexanet alpha 的 RR 分别为 1.74（95% CI 1.09-2.77）和 1.71（95% CI 1.01-2.89）（I2 = 0%）。考虑到回顾性研究，共同效应模型的汇总RR为1.21（95% CI 0.87-1.69），随机效应模型的汇总RR为1.18（95% CI 0.86-1.62）（I2 = 0%）：考虑到大量回顾性研究和对照研究，在死亡率方面，Andexanet alpha 与 4F-PCC 相比并没有显示出统计学上的显著优势。仅就对照研究进行分析，Andexanet alpha 与血栓栓塞事件风险增加有关：临床试验注册：PROSPERO：国际前瞻性系统综述注册，2024，CRD42024548768。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Critical Care 医学-危重病医学

CiteScore

20.60

自引率

3.30%

发文量

348

审稿时长

1.5 months

期刊介绍： Critical Care is an esteemed international medical journal that undergoes a rigorous peer-review process to maintain its high quality standards. Its primary objective is to enhance the healthcare services offered to critically ill patients. To achieve this, the journal focuses on gathering, exchanging, disseminating, and endorsing evidence-based information that is highly relevant to intensivists. By doing so, Critical Care seeks to provide a thorough and inclusive examination of the intensive care field.