1. In this randomized controlled trial, among patients presenting with acute intracerebral hemorrhage (ICH) who had taken factor Xa inhibitors, andexanet resulted in less hematoma expansion compared to usual care.
2. Andexanet was associated with higher risks of thrombotic events, including ischemic stroke, and no difference in modified Rankin scale or death at 30 days.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Factor Xa inhibitors are anticoagulants that prevent thrombotic events. Nevertheless, these medications increase the risk of hemorrhage, with acute ICH resulting in significant disability and mortality, where hematoma expansion is a predictor of poor outcomes. Andexanet is a recombinant inactive factor Xa that inactivates factor Xa inhibitors and restores thrombin function. This trial compared andexanet against usual care for patients on factor Xa inhibitors presenting with acute ICH. The composite hemostatic efficacy outcome at 12 hours of attenuated hematoma expansion and deterioration on the National Institutes of Health Stroke Scale (NIHSS) and no receipt of rescue therapy occurred in significantly more patients receiving andexanet than usual care. However, there was no difference in the scores on the modified Rankin scale or death at 30 days. Andexanet was associated with a higher risk of thrombotic events, including ischemic strokes. Although the trial was underpowered to detect changes in the modified Rankin scale scores and death, these results suggested that andexanet reduced hematoma expansion in patients with acute ICH on factor Xa inhibitors while increasing the risk of thrombotic events.
Click here to read the study in NEJM
In-Depth [randomized controlled trial]: This study was a randomized controlled trial comparing andexanet against usual care for the treatment of acute ICH among patients who had been receiving a factor Xa inhibitor. Patients who were receiving a factor Xa inhibitor with the last dose taken within 15 hours before randomization and presented with an acute factor Xa inhibitor-associated ICH as the main bleeding event, with a hematoma volume of 0.5-60mL and a maximum score on the NIHSS of 35, and had received baseline imagine scan of ≤6 hours from bleeding onset, were eligible for inclusion. Exclusion criteria included a Glasgow Coma Scale of less than seven at the time of consent, NIHSS score greater than three, planned surgery within 12 hours, or a thrombotic event within two weeks of presentation. In total, 550 patients were randomized 1:1 to receive either andexanet or usual care. The primary outcome was hemostatic efficacy at 12 hours. The most common indication for factor Xa inhibitors was atrial fibrillation. A total of 85.5% of patients in the usual care group received prothrombin complex concentrate. Hemostatic efficacy was achieved in 67.0% of patients receiving andexanet and 53.1% of those receiving usual care (adjusted difference [AD], 13.4 percentage points; 95% confidence interval [CI], 4.6-22.2; p=0.003). The median reduction from baseline to nadir in anti-factor Xa activity was 94.5% in the andexanet group and 26.9% in the usual care group (p<0.001). Notably, andexanet was associated with an increased risk of thrombotic events (10.3%) compared to usual care (5.6%) (p=0.0048). However, there was no difference in mortality at 30 days between the two groups: 27.8% and 25.5%, respectively (p=0.51), nor was there a difference in the modified Rankin Scale outcome. In summary, these results demonstrated that for patients with an acute factor Xa inhibitor-associated ICH, andexanet reduced hematoma expansion and increased hemostatic efficacy at the cost of increasing the risk of thrombotic events, including ischemic stroke.
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