In this episode, I’ll discuss using Andexanet Alfa vs Prothrombin Complex Concentrate for factor Xa inhibitor reversal in acute major bleeding.
There are two methods used for reversing acute major bleeding from factor Xa inhibitors:
1. Prothrombin Complex Concentrate (PCC), which is an indirect reversal strategy that attempts to create a pro-coagulant effect by providing extra clotting factors II, VII, IX, and X.
2. Andexanet alfa, which acts as a direct reversal agent by binding and inactivating circulating factor Xa inhibitors
To date there has not been a prospective head-to-head comparison of these two strategies.
Recently in the journal Critical Care Medicine, researchers published a meta-analysis that sought to analyze the available evidence for each of these strategies and compare them as best as the limits of this type of analysis will allow. Hemostatic effectiveness and venous thromboembolic events were compared for each agent.
21 studies with over 1700 patients were analyzed. Studies using PCC had approximately 3 times as many patients as those using andexanet alfa.
The authors found the following results:
At 12 hours the mean effectiveness for andexanet alfa was 82% vs 88% for PCC.
At 24 hours the mean effectiveness for andexanet alfa was 71% vs 76% for PCC.
At 30 days the mean 30-day total thrombotic event rates for andexanet alfa was 10.7% vs 3.1% for PCC.
The mean in-hospital mortality for andexanet alfa was 23.3% vs 15.8% for PCC.
Despite these figures suggesting a numerically better result from PCC, the authors conducted an exploratory analysis that controlled for potential confounders which did not demonstrate statistically significant differences between either agent for hemostatic efficacy, thrombosis, or mortality.
The authors concluded:
Currently, available evidence does not unequivocally support the clinical effectiveness of andexanet alfa or PCC to reverse FXaIs in the setting of acute major bleeding, nor does it permit conventional meta-analysis to study potential superiority. In exploratory analysis of observational studies, neither reversal agent was significantly associated with increased effectiveness or higher rate of (venous) thromboembolism. These results underscore the importance of
randomized controlled trials comparing the two reversal agents and may provide guidance in designing institutional guidelines.
To the extent that this meta-analysis is a representation of real-world use of these two agents, this analysis suggests that despite andexanet alfa’s higher quality of evidence, a conclusion of superiority cannot be drawn and it may be reasonable to consider either agent until definitive data becomes available.
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