Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures.

BACKGROUND: Outcomes following andexanet alfa reversal of factor Xa inhibitors in patients requiring urgent or emergent invasive procedures are lacking. This study aimed to describe efficacy and safety outcomes following andexanet alfa administration within 24 h of an invasive procedure. METHODS: This single-center, observational, retrospective study included patients who received andexanet alfa within 24 h of an invasive or surgical procedure. The primary outcome was hemostatic efficacy graded as excellent, good, or poor using similar definitions to the ANNEXA-4 criteria. Secondary outcomes included hospital discharge disposition, intensive care unit (ICU) and hospital length of stay, 30-day mortality, 30-day thromboischemic event rates, and serum coagulation assay changes pre- and postreversal. RESULTS: Forty-four patients met inclusion criteria; of these, 27 (62.8%) received apixaban and 16 (37.2%) were treated with rivaroxaban prior to admission. The indications for reversal were categorized as intracranial (n = 20 [45.5%]) or extracranial (n = 24 [54.5%]) sites. Majority of patients required emergent operative procedures (18 [40.9%]), followed by invasive device placement (10 [22.7%]) or arterial embolization (9 [20.5%]). Thirty-eight (86.4%) patients were able to be adequately graded for hemostatic efficacy. Overall, 30 (78.9%) patients achieved excellent or good hemostasis within 24 h after periprocedural administration of andexanet alfa (19 [82.6%] apixaban vs. 11 [78.6%] rivaroxaban; 12 [80.0%] intracranial events vs. 18 [78.3%] extracranial events). Discharge disposition was most often to a short- or long-term care facilities (27 [61.4%]). Thirty-day mortality and thromboischemic complications occurred in 15 (34.1%) and 12 (27.3%) patients, respectively. Prothrombin time and antifactor Xa assay results were significantly decreased after andexanet alfa administration (p < 0.05) while thromboelastogram assay values (reaction time, kinetic time, and activated clotting time) showed nonsignificant changes pre- versus postreversal. CONCLUSION: Andexanet alfa may be used for urgent or emergent reversal of apixaban and rivaroxaban peri-procedurally with promising hemostatic outcomes. Further prospective, comparative clinical research is warranted.

Comparative hemostatic efficacy of 4F-PCC in patients with intracranial hemorrhage on factor Xa inhibitors versus warfarin.

OBJECTIVE: Patients experiencing an intracranial hemorrhage (ICH) on oral anticoagulants often require rapid reversal. This study evaluated patients taking factor Xa inhibitors or warfarin that received reversal with 4-factor prothrombin complex concentrate (4F-PCC) for an ICH. The objective of the study was to determine if the efficacy of 4F-PCC for the reversal of factor Xa inhibitors is noninferior to its use in warfarin reversal in patients with ICH. METHODS: This was a retrospective, single center, noninferiority trial. Patients presenting to the emergency department with ICH were divided into two cohorts: those taking factor Xa inhibitors versus those taking warfarin. In each cohort, patients received anticoagulation reversal with weight-based 4F-PCC. The primary endpoint was hemostatic efficacy defined as ≤20% expansion in hematoma volume on repeat computed tomography imaging. A pre-specified noninferiority margin of -10% was selected to evaluate the difference between groups for the primary endpoint. RESULTS: A total of 221 patients were included in the study (factor Xa inhibitors, n = 87; warfarin, n = 134). Effective hemostasis was achieved in 70 patients (81%) on factor Xa inhibitors compared to 111 patients (83%) on warfarin, (-2.4% difference, [95% confidence interval, -12.87 to 8.12]; p = 0.654). There was no statistically significant difference between groups with regards to the primary outcome; however, the use of 4F-PCC in factor Xa inhibitor reversal was not noninferior when compared to 4F-PCC use for warfarin reversal. Hospital length of stay and discharge disposition were similar between cohorts. CONCLUSIONS: The efficacy of 4F-PCC in reversing factor Xa inhibitor-related ICH compared to warfarin-related ICH was not significantly different between groups; however, these results did not prove noninferiority. Further study is warranted to delineate 4F-PCC's role in reversing factor Xa inhibitors in patients with ICH.

Factors associated with availability of anticoagulation reversal agents in rural and community emergency departments.

PURPOSE: Results of a study of anticoagulation reversal agent availability in rural and community hospital emergency departments (EDs) are reported. METHODS: A cross-sectional telephone survey was conducted to test the hypothesis that anticoagulation reversal agents are not commonly stocked in low-volume EDs. In phase 1 of the study, a physician, pharmacist, or nurse manager at a sample of EDs in 1 state was surveyed to characterize anticoagulation reversal agent availability and the presence or absence of reversal protocols; in phase 2, follow-up qualitative interviews were conducted with hospital pharmacists selected by purposive sampling to identify barriers to availability. RESULTS: Among the 103 EDs represented in the survey, 87 (84%) stocked fresh frozen plasma, 14 (14%) stocked 4-factor prothrombin complex concentrate (4F-PCC), and 2 (2%) stocked activated 4F-PCC. Forty-one EDs (40%) had a warfarin reversal protocol, but only 2 (2%) EDs had a protocol for direct oral anticoagulant reversal. ED volume and neurology coverage were significantly associated with reversal agent availability (p = 0.014) and warfarin protocol availability (p < 0.001). Identified factors contributing to reversal agent nonavailability were product cost, lack of knowledge of drug availability, and concerns about shelf life. CONCLUSION: An investigation of rural and community hospitals in 1 state revealed that the institutions rarely have specialized anticoagulation reversal drugs available. Cost and infrequency of utilization were 2 commonly cited reasons for reversal agent nonavailability.