Science, Medicine, and the Anesthesiologist

Patients sustaining acute intracerebral hemorrhage on anticoagulants are at increased risk for hematoma expansion. Factor Xa inhibitors are now widely used for chronic anticoagulation, and before the release of andexanet alfa, no specific reversal agents were available. The effects of andexanet alfa on hematoma volume expansion in a randomized study have not been previously reported. This multicenter study (131 sites, 23 countries) evaluated its use versus usual care (primarily prothrombin complex concentrates). Patients receiving factor Xa inhibitors within 15 h before an acute intracerebral hemorrhage were randomized to either andexanet (N = 263) or usual care (N = 267). The primary outcome was hemostatic efficacy (a composite of radiographic hematoma expansion, increase in National Institutes of Health Stroke Scale score, and receipt of rescue therapy). Safety outcomes included thrombotic events and death. Atrial fibrillation was present in 84 (usual) to 90% (andexanet) of subjects. The primary outcome was significantly lower in the andexanet group (67% vs. 53.1%; adjusted difference, 13.4 percentage points; 95% CI, 4.6 to 22.2; P = 0.003). Adverse safety outcomes were higher with andexanet (thrombosis, 10.3% vs. 5.6%, P = 0.048; ischemic stroke, 6.5% vs. 1.5%). No difference occurred in 30-day mortality.

Take home message: In this randomized multicenter trial, reversal of anticoagulation during acute intracerebral hemorrhage in the setting of prior factor Xa inhibitor use with andexanet was associated with improved hemostatic efficacy compared to usual care, although more adverse safety events occurred with its use.