Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors.

Andexanet alfa is a modified recombinant inactive form of human factor Xa developed for reversal of factor Xa inhibitors. We evaluated 352 patients who had acute major bleeding within 18 hours after administration of a factor Xa inhibitor. The patients received a bolus of andexanet, followed by a 2-hour infusion. The coprimary outcomes were the percent change in anti-factor Xa activity after andexanet treatment and the percentage of patients with excellent or good hemostatic efficacy at 12 hours after the end of the infusion, with hemostatic efficacy adjudicated on the basis of prespecified criteria. Efficacy was assessed in the subgroup of patients with confirmed major bleeding and baseline anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.25 IU per milliliter for those receiving enoxaparin). Patients had a mean age of 77 years, and most had substantial cardiovascular disease. Bleeding was predominantly intracranial (in 227 patients [64%]) or gastrointestinal (in 90 patients [26%]). In patients who had received apixaban, the median anti-factor Xa activity decreased from 149.7 ng per milliliter at baseline to 11.1 ng per milliliter after the andexanet bolus (92% reduction; 95% confidence interval [CI], 91 to 93); in patients who had received rivaroxaban, the median value decreased from 211.8 ng per milliliter to 14.2 ng per milliliter (92% reduction; 95% CI, 88 to 94). Excellent or good hemostasis occurred in 204 of 249 patients (82%) who could be evaluated. Within 30 days, death occurred in 49 patients (14%) and a thrombotic event in 34 (10%). Reduction in anti-factor Xa activity was not predictive of hemostatic efficacy overall but was modestly predictive in patients with intracranial hemorrhage. In patients with acute major bleeding associated with the use of a factor Xa inhibitor, treatment with andexanet markedly reduced anti-factor Xa activity, and 82% of patients had excellent or good hemostatic efficacy at 12 hours, as adjudicated according to prespecified criteria. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327.).

Connolly SJ ，Crowther M ，Eikelboom JW ，Gibson CM ，Curnutte JT ，Lawrence JH ，Yue P ，Bronson MD ，Lu G ，Conley PB ，Verhamme P ，Schmidt J ，Middeldorp S ，Cohen AT ，Beyer-Westendorf J ，Albaladejo P ，Lopez-Sendon J ，Demchuk AM ，Pallin DJ ，Concha M ，Goodman S ，Leeds J ，Souza S ，Siegal DM ，Zotova E ，Meeks B ，Ahmad S ，Nakamya J ，Milling TJ Jr ，ANNEXA-4 Investigators ... -  《-》

Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.

Connolly SJ ，Milling TJ Jr ，Eikelboom JW ，Gibson CM ，Curnutte JT ，Gold A ，Bronson MD ，Lu G ，Conley PB ，Verhamme P ，Schmidt J ，Middeldorp S ，Cohen AT ，Beyer-Westendorf J ，Albaladejo P ，Lopez-Sendon J ，Goodman S ，Leeds J ，Wiens BL ，Siegal DM ，Zotova E ，Meeks B ，Nakamya J ，Lim WT ，Crowther M ，ANNEXA-4 Investigators ... -  《-》

Final Study Report of Andexanet Alfa for Major Bleeding With Factor Xa Inhibitors.

Milling TJ Jr ，Middeldorp S ，Xu L ，Koch B ，Demchuk A ，Eikelboom JW ，Verhamme P ，Cohen AT ，Beyer-Westendorf J ，Gibson CM ，Lopez-Sendon J ，Crowther M ，Shoamanesh A ，Coppens M ，Schmidt J ，Albaladejo P ，Connolly SJ ，ANNEXA-4 Investigators ... -  《-》

Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity.

Siegal DM ，Curnutte JT ，Connolly SJ ，Lu G ，Conley PB ，Wiens BL ，Mathur VS ，Castillo J ，Bronson MD ，Leeds JM ，Mar FA ，Gold A ，Crowther MA ... -  《-》

Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy.

Demchuk AM ，Yue P ，Zotova E ，Nakamya J ，Xu L ，Milling TJ Jr ，Ohara T ，Goldstein JN ，Middeldorp S ，Verhamme P ，Lopez-Sendon JL ，Conley PB ，Curnutte JT ，Eikelboom JW ，Crowther M ，Connolly SJ ，ANNEXA-4 Investigators ... -  《-》