title: Andexanet alfa for the reversal of anticoagulant activity in patients treated with direct and indirect factor Xa inhibitors.
abstract: Andexanet alfa is a recombinant factor Xa decoy molecule that inhibits direct and indirect factor Xa inhibitors to allow the normal coagulation process to resume. Its development arises in a space where novel oral anticoagulants are receiving expanded indications yet their use is limited by the lack of an effective reversal agent. Areas covered: This article reviews the biochemical properties, mechanism of action and the preclinical and clinical trials on andexanet alfa. It additionally aims to provide expert commentary and future perspectives on the efficacy, safety and challenges facing andexanet alfa as a universal antidote for direct and indirect factor Xa inhibitors. Expert commentary: Andexanet alfa shows promise to become a highly effective, novel antidote for factor Xa anticoagulation. Its biochemical profile and mechanism of action are immediately more attractive than other drugs on the market and under development due to its inert nature within the normal coagulation cascade, with minimal intrinsic procoagulant or anticoagulant properties. The anticoagulant antidote space will continue to develop as more specific and universal options become available for reversal of the effect of DOACs. Preliminary results of a pivotal phase 3b/4 trial demonstrate a favorable efficacy and safety profile in patients with acute hemorrhage.
authors.affiliation: a PERFUSE Study Group, Cardiovascular Division, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Tarek
authors.initials: T
authors.lastname: Nafee
authors.affiliation: a PERFUSE Study Group, Cardiovascular Division, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Aysha
authors.initials: A
authors.lastname: Aslam
authors.affiliation: a PERFUSE Study Group, Cardiovascular Division, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Chi
authors.affiliation: a PERFUSE Study Group, Cardiovascular Division, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Seyedmahdi
authors.initials: S
authors.lastname: Pahlavani
authors.affiliation: a PERFUSE Study Group, Cardiovascular Division, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Dima
authors.initials: D
authors.lastname: Nimri
authors.affiliation: a PERFUSE Study Group, Cardiovascular Division, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Aravind Reddy
authors.initials: AR
authors.lastname: Kuchkuntla
authors.affiliation: a PERFUSE Study Group, Cardiovascular Division, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Usama
authors.initials: U
authors.lastname: Talib
authors.affiliation: a PERFUSE Study Group, Cardiovascular Division, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Michalak
authors.affiliation: a PERFUSE Study Group, Cardiovascular Division, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Yazan
authors.initials: Y
authors.lastname: Daaboul
authors.affiliation: a PERFUSE Study Group, Cardiovascular Division, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Serge
authors.initials: S
authors.lastname: Korjian
authors.affiliation: a PERFUSE Study Group, Cardiovascular Division, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Gallo
authors.affiliation: a PERFUSE Study Group, Cardiovascular Division, Department of Medicine , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D000931:Antidotes / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D015951:Factor Xa / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006470:Hemorrhage / Q000188:drug therapy; D006801:Humans; D011994:Recombinant Proteins / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D000931:Antidotes; D065427:Factor Xa Inhibitors; C580915:PRT064445; D011994:Recombinant Proteins; D015951:Factor Xa
keywords: Andexanet alfa; DOAC; anticoagulation; antidote; factor Xa; reversal agents