Andexanet alfa for acute major bleeding associated with factor xa inhibitors

Stuart J. Connolly, Truman J. Milling, John W. Eikelboom, C. Michael Gibson, John T. Curnutte, Alex Gold, Michele D. Bronson, Genmin Lu, Pamela B. Conley, Peter Verhamme, Jeannot Schmidt, Saskia Middeldorp, Alexander T. Cohen, Jan Beyer-Westendorf, Pierre Albaladejo, Jose Lopez-Sendon, Shelly Goodman, Janet Leeds, Brian L. Wiens, Deborah M. SiegalElena Zotova, Brandi Meeks, Juliet Nakamya, W. Ting Lim, Mark Crowther, R. Anand, A. Bastani, J. Caterino, C. Clark, M. Concha, J. Cornell, E. Eriksson, G. Fermann, J. Fulmer, J. Goldstein, D. Kereiakes, S. Lotfipour, S. Moll, D. Pallin, N. Patel, M. Refaai, M. Rehman, A. Schmaier, E. Schwarz, W. Shillinglaw, R. Sinert, A. Singer, L. Smith, T. Takata, A. Venkat, D. Weinstein, J. Welker, I. Welsby, S. Wiener, J. Wilson, M. Blostein, L. Van Keer, F. Verschuren, M. Coppens, S. van Wissen, R. Alikhan, K. Breen, R. Hall

Research output: Contribution to journalArticlepeer-review

555 Scopus citations

Abstract

Background Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. METHODS In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication. RESULTS The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti- factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up. CONCLUSIONS On the basis of a descriptive preliminary analysis, an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti-factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors, with effective hemostasis occurring in 79%.

Original languageEnglish
Pages (from-to)1131-1141
Number of pages11
JournalNew England Journal of Medicine
Volume375
Issue number12
DOIs
StatePublished - Sep 22 2016

Fingerprint

Dive into the research topics of 'Andexanet alfa for acute major bleeding associated with factor xa inhibitors'. Together they form a unique fingerprint.

Cite this