Written by Megan Hilbert
For direct oral anticoagulant related intracranial hemorrhage (ICH), andexanet was more likely than prothrombin complex concentrate (PCC) to prevent worsening of hemorrhage but was associated with more thrombotic events (TE).
The tightrope that is reversal of anticoagulation
This retrospective observational study evaluated the primary hemostatic efficacy of andexanet versus PCC and the occurrence of thrombotic events for patients with ICH. There was increased frequency of hemostasis in the andexanet compared to PCC (odds ratio, OR 1.60; 95%CI 1.00-2.56), but andexanet patients had higher odds of TE (OR 1.91; 95%CI 1.13-3.20; p=0.014). Mortality was comparable. The study was underpowered to demonstrate non-inferiority* between the two products.
This study is very similar to the ANNEXa-I trial (a prospective randomized trial – arguably stronger in study design overall). Where this study differs and excels is the inclusion of a broad array of intracranial hemorrhage etiologies (SDH, SAH, etc.), inclusion of patients with planned neurosurgical procedures, as well as inclusion of patients with GCS less than 7. Theoretically, this is more representative of the overall patient population, but unfortunately, the subgroup analysis did not demonstrate any meaningful statistical outcomes.
How does this change my practice?
The authors note that this paper is “hypothesis-generating only” (particularly in relation to mortality data). I am inclined to agree, and this will not change my practice yet. I will continue to reach for PCC, given my comfort with the product both in dosing and in nursing experience with administration.
Another Spoonful
There are cost considerations as well. An AHA study found, “There is a significant difference in cost between the 2 options, with the single bolus and infusion of Andexanet having an estimated cost of $25 000 or $50 000 US dollars (standard dose versus high dose respectively, depending on patient characteristics) compared with ≈$4000 to 8000 US dollars for PCC.”
*Editor’s note: Determining non-inferiority is possible but not best in a retrospective study. It’s impossible to ensure the non-inferiority margin, which is chosen after collection of all the data – by definition – in a retrospective study, is not based on data dredging. Regardless, in this study, they did not find non-inferiority. ~Clay Smith
Source
Reversal of Factor Xa Inhibitor-Related Intracranial Hemorrhage: A Multicenter, Retrospective, Observational Study Comparing the Efficacy and Safety of Andexanet and Prothrombin Complex Concentrates. Crit Care Med. 2025 Apr 2. doi: 10.1097/CCM.0000000000006656. Epub ahead of print. PMID: 40172261
