背景:目前缺乏证据证明Andexanetα和四因子凝血酶原复合物浓缩物(4F-PCC)在直接口服抗凝剂(DOAC)的抗凝逆转中的相对有效性。我们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恢复策略中哪一种受血栓栓塞事件的影响较小。
方法:进行系统评价和荟萃分析。
结果:在系统评价和定量综合中分析了22项研究。在全因短期死亡率中,Andexanetα在RCT和PSM中显示出0.71的风险比(RR)(95%CI0.37-1.34),与4F-PCC相比(I2=81%)。考虑到回顾性研究,合并的RR对于共同效应模型为0.84(95%CI0.69-1.01),对于随机效应模型为0.82(95%CI0.63-1.07)(I2=34.2%).关于血栓栓塞事件的发生率,对于RCT和PSM,共同效应和随机效应模型的RR为1.74(95%CI1.09-2.77),和1.71(95%CI1.01-2.89),分别,与4F-PCC相比,Andexanetα(I2=0%)。考虑到回顾性研究,合并的RR对于共同效应模型为1.21(95%CI0.87-1.69),对于随机效应模型为1.18(95%CI0.86-1.62)(I2=0%).
结论:考虑到大量的回顾性和对照研究,Andexanetα在死亡率方面没有显示出超过4F-PCC的统计学显著优势。仅在对照研究的分析中,Andexanetα与血栓栓塞事件的风险增加相关。
背景:PROSPERO:系统评价的国际前瞻性注册,2024,CRD42024548768。
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%).
CONCLUSIONS: 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.
BACKGROUND: PROSPERO: International prospective register of systematic reviews, 2024, CRD42024548768.