Azienda Sanitaria Universitaria Friuli Centrale, Department of Emergency "Santa Maria Della Misericordia", University Hospital of Udine, Piazzale Santa Maria Della Misericordia, N.15, 33100, Udine, UD, Italy.
Department of Medicine, University of Udine, via Colugna 50, 33100, Udine, Italy.
Crit Care. 2024 Jul 5;28(1):221. doi: 10.1186/s13054-024-05014-x.
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.
A systematic review and meta-analysis was performed.
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 (I = 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 (I = 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 (I = 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 (I = 0%).
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.
PROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768.
目前，关于抗凝血逆转直接口服抗凝剂（DOACs）时，安加奈特α与四种因子凝血酶原复合物浓缩物（4F-PCC）的比较有效性，尚无相关证据。本系统评价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种受血栓栓塞事件的影响较小。
进行了系统评价和荟萃分析。
系统评价和定量综合分析共纳入 22 项研究。在所有短期全因死亡率方面，与 4F-PCC 相比，RCT 和 PSM 中安加奈特α的风险比（RR）为 0.71（95%CI 0.37-1.34）（I=81%）。考虑到回顾性研究，在共同影响模型中，汇总 RR 为 0.84（95%CI 0.69-1.01），在随机效应模型中，汇总 RR 为 0.82（95%CI 0.63-1.07）（I=34.2%）。关于血栓栓塞事件的发生率，对于 RCT 和 PSM，共同和随机效应模型显示，与 4F-PCC 相比，安加奈特α的 RR 分别为 1.74（95%CI 1.09-2.77）和 1.71（95%CI 1.01-2.89）（I=0%）。考虑到回顾性研究，在共同影响模型中，汇总 RR 为 1.21（95%CI 0.87-1.69），在随机效应模型中，汇总 RR 为 1.18（95%CI 0.86-1.62）（I=0%）。
考虑到大量回顾性和对照研究，与 4F-PCC 相比，安加奈特α在死亡率方面没有表现出统计学上的显著优势。在单独分析对照研究时，安加奈特α与血栓栓塞事件的风险增加相关。
PROSPERO：国际系统评价前瞻性登记，2024 年，CRD42024548768。
