Clinical Pearls & Morning Reports
Acute major bleeding that is associated with the use of factor Xa inhibitors can be a medical emergency with a poor prognosis. There are limited treatment options for such patients. Connolly et al. recently published the full report of their single-group cohort study that assessed the efficacy and safety of andexanet in patients with acute major bleeding occurring while taking a factor Xa inhibitor (interim results from the first 67 patients treated in this study were published previously). Read the Original Article here.
Q: What is andexanet alfa?
A: Andexanet alfa is a modified recombinant inactive form of human factor Xa designed specifically to bind and sequester factor Xa inhibitor molecules, thereby rapidly reducing anti–factor Xa activity, a measure of the anticoagulant effect of factor Xa inhibitors.
Q: How effective was andexanet in reducing factor Xa activity among patients who had major bleeding with the use of apixaban or rivaroxaban?
A: In the trial by Connolly et al., treatment with andexanet markedly reduced anti–factor Xa activity. In the efficacy population, among the 134 patients who were receiving apixaban, the median value for anti–factor Xa activity was reduced from 149.7 ng per milliliter at baseline to 11.1 ng per milliliter at the end of the bolus administration, a 92% reduction (95% confidence interval [CI], 91 to 93). Among the 100 patients who were receiving rivaroxaban, the median value for anti–factor Xa activity fell from 211.8 ng per milliliter at baseline to 14.2 ng per milliliter at the end of the bolus administration, a 92% reduction (95% CI, 88 to 94). At 4, 8, and 12 hours after the subsequent 2-hour andexanet infusion, the median value for anti–factor Xa activity was reduced from baseline by 32%, 34%, and 38%, respectively, for apixaban and by 42%, 48%, and 62%, respectively, for rivaroxaban.
A: Of the 254 patients in the efficacy analysis, 249 could be evaluated for hemostatic efficacy, and 204 (82%) were adjudicated as having excellent or good hemostatic efficacy at 12 hours (95% CI, 77 to 87). Of these, 171 were adjudicated as having excellent hemostatic efficacy and 33 as having good hemostatic efficacy. The percentages of patients with excellent or good efficacy were 85% (95% CI, 76 to 94) for gastrointestinal bleeding and 80% (95% CI, 74 to 86) for intracranial bleeding. Reduction in anti–factor Xa activity was not predictive of hemostatic efficacy overall but was modestly predictive in patients with intracranial hemorrhage.
A: Patients receive factor Xa inhibitors because they are at high risk for thrombotic events. Abrupt discontinuation of anticoagulation, coincident with acute bleeding, accentuates this risk. In the study, 14% of the patients died and there were thrombotic events in 10%. Not surprisingly, a majority of events occurred in patients in whom resumption of oral anticoagulation was delayed or in patients who did not restart anticoagulation. After restarting of oral anticoagulation, no patient had a thrombotic event during the 30-day follow-up.