Key result
Andexanet alpha did not show a statistically significant advantage over 4F-PCC in reducing short-term all-cause mortality (RR 0.71 in controlled studies), but was associated with an increased risk of thromboembolic events.
Why the study?
Evidence was lacking on the comparative effectiveness of Andexanet alpha versus four-factor prothrombin complex concentrate for direct oral anticoagulant reversal.
Does Andexanet alpha reduce short-term all-cause mortality compared to 4F-PCC in adults requiring DOAC anticoagulation reversal for haemorrhage?
Meta-Analysis (n=3,450)
Does Andexanet alpha reduce short-term all-cause mortality compared to 4F-PCC in adults requiring DOAC anticoagulation reversal for haemorrhage?
Andexanet alpha did not show a statistically significant advantage over 4F-PCC for short-term mortality in DOAC reversal, but was associated with an increased risk of thromboembolic events in controlled studies.
No mortality benefit for andexanet versus 4F-PCC; leaves optimal reversal choice open pending thromboembolic risk data.
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 (I 2 = 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 2 = 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 2 = 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 2 = 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.
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Orso et al. (2024) conducted a meta-analysis in Direct oral anticoagulant (DOAC) associated hemorrhage (n=3,450). Andexanet alpha vs. Four-factor prothrombin complex concentrate (4F-PCC) was evaluated on Short-term all-cause mortality (RR 0.71, 95% CI 0.37-1.34). Andexanet alpha did not show a statistically significant advantage over 4F-PCC in reducing short-term all-cause mortality (RR 0.71 in controlled studies), but was associated with an increased risk of thromboembolic events.
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