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 (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%). 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.

中文翻译：

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Andexanet α 与四因子凝血酶原复合物浓缩物在 DOAC 抗凝逆转中的作用：更新的系统评价和荟萃分析


目前缺乏证据证明 Andexanet α 和四因子凝血酶原复合物浓缩物 (4F-PCC) 在逆转直接口服抗凝剂 (DOAC) 的抗凝作用方面的比较有效性。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。第二个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。进行了系统评价和荟萃分析。对 22 项研究进行了系统评价和定量综合分析。在全因短期死亡率方面，与 4F-PCC (I2 = 81%) 相比，Andexanet α 在 RCT 和 PSM 中显示的风险比 (RR) 为 0.71 (95% CI 0.37–1.34)。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，对于 RCT 和 PSM，与 Andexanet α 相比，共同效应模型和随机效应模型的 RR 分别为 1.74 (95% CI 1.09–2.77) 和 1.71 (95% CI 1.01–2.89)。至 4F-PCC（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%)。考虑到大量回顾性和对照研究，Andexanet alpha 在死亡率方面并未显示出比 4F-PCC 具有统计学上显着的优势。仅在对照研究的分析中，Andexanet α 与血栓栓塞事件风险增加相关。 PROSPERO：国际前瞻性系统评价登记册，2024 年，CRD42024548768。