Department of General Practice, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, P.R. China.
Eur Rev Med Pharmacol Sci. 2021 Mar;25(6):2637-2653. doi: 10.26355/eurrev_202103_25428.
There are potential concerns related to bleeding caused by oral anticoagulants, especially in the elderly. Andexanet alfa has been authorized for use to reverse the effects of oral anticoagulants. Off-label use of four factor prothrombin complex concentrate (4F-PCC) for the reversal of oral factor Xa inhibitors is common. However, not much is known about their efficacy and safety profile. The intent of this meta-analysis was to evaluate the efficacy and safety of 4F-PCC and andexanet alfa for management of major bleeding due to oral factor Xa inhibitors. Comprehensive searches were done systematically through PubMed, Scopus and Google scholar databases. Studies that were retrospective record based or adopted prospective cohort approach and reported either of the three main outcomes, i.e., achieved hemostasis rate or rate of thrombotic events or mortality rate were included in the meta-analysis. Statistical analyses were done using STATA version 13.0. A total of 22 studies were included in the meta-analysis. All the studies had a single arm with no control/comparator group. The pooled rate of good to excellent hemostatic control upon use of andexanet was 80% (95% CI; 72% to 88%) and for 4F-PCC, it was 76% (95% CI; 70% to 83%). A comparatively higher pooled rate of thrombotic complications upon use of andexanet [13% (95% CI; 5% to 20%) was noted, compared to use of aPCC/4F-PCC [4% (95% CI; 3% to 5%). The pooled all-cause mortality rate within 30 days of administration was 24% (95% CI; 12% to 35%) with andexanet use and 19% (95% CI; 14% to 25%) for aPCC/4F-PCC. The findings suggest that use of both andexanet and aPCC/4F-PCC achieves a good hemostasis but there is an associated risk of thrombotic events and mortality. Future studies should have a control group to better establish evidence on efficacy and safety of these agents.
存在与口服抗凝剂引起的出血相关的潜在问题，尤其是在老年人中。Andexanet alfa 已被授权用于逆转口服抗凝剂的作用。非适应证使用四因子凝血酶原复合物浓缩物（4F-PCC）逆转口服 Xa 因子抑制剂是常见的。然而，对于其疗效和安全性概况了解甚少。本荟萃分析的目的是评估 4F-PCC 和 Andexanet alfa 用于治疗口服 Xa 因子抑制剂引起的大出血的疗效和安全性。通过 PubMed、Scopus 和 Google Scholar 数据库进行全面系统的搜索。纳入的研究采用回顾性记录或前瞻性队列方法，报告以下三个主要结局之一，即达到止血率、血栓形成事件发生率或死亡率。使用 STATA 版本 13.0 进行统计分析。共有 22 项研究纳入荟萃分析。所有研究均为单臂研究，无对照组/比较组。使用 Andexanet 达到良好至极好止血控制的总体有效率为 80%（95%CI：72%至 88%），而使用 4F-PCC 的有效率为 76%（95%CI：70%至 83%）。使用 Andexanet 时血栓并发症的总体发生率较高[13%（95%CI：5%至 20%），而使用 aPCC/4F-PCC 时为 4%（95%CI：3%至 5%）。使用 Andexanet 的 30 天内全因死亡率为 24%（95%CI：12%至 35%），使用 aPCC/4F-PCC 的死亡率为 19%（95%CI：14%至 25%）。研究结果表明，使用 Andexanet 和 aPCC/4F-PCC 均可达到良好的止血效果，但存在血栓形成事件和死亡的风险。未来的研究应该有对照组，以更好地确定这些药物的疗效和安全性证据。
