PMID- 37635060
OWN - NLM
STAT- MEDLINE
DCOM- 20240305
LR  - 20240309
IS  - 1880-3873 (Electronic)
IS  - 1340-3478 (Print)
IS  - 1340-3478 (Linking)
VI  - 31
IP  - 3
DP  - 2024 Mar 1
TI  - Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity: Prespecified 
      Subgroup Analysis of the ANNEXA-4 Study in Japan.
PG  - 201-213
LID - 10.5551/jat.64223 [doi]
AB  - AIMS: Andexanet alfa, a specific antidote to factor Xa (FXa) inhibitors, has been 
      approved for clinical use in several countries, including Japan, based on the 
      results from the phase 3 trial ANNEXA-4. We aimed to assess the efficacy and 
      safety of andexanet alfa treatment in FXa inhibitor-related acute major bleeding 
      in patients enrolled for ANNEXA-4 in Japan. METHODS: This prespecified analysis 
      included patients enrolled at Japanese sites in the prospective, open-label, 
      single-arm ANNEXA-4 trial. Eligible patients had major bleeding within 18 hours 
      of oral FXa inhibitor administration. The coprimary efficacy endpoints were 
      percent change in anti-FXa activity and proportion of patients achieving 
      excellent or good hemostatic efficacy 12 hours post-treatment. RESULTS: A total 
      of 19 patients were enrolled, all of whom had intracranial hemorrhage; 16 
      patients were evaluable for efficacy. Median percent reduction in anti-FXa 
      activity from baseline to nadir was 95.4% in patients taking apixaban, 96.1% in 
      patients taking rivaroxaban, and 82.2% in patients taking edoxaban. Overall, 
      14/16 patients (88%) achieved excellent or good hemostasis (apixaban, 5/5; 
      rivaroxaban, 6/7; edoxaban, 3/4). Within 30 days, treatment-related adverse 
      events (AEs) and serious AEs occurred in 2 and 5 patients, respectively. One 
      patient died during follow-up, and 2 patients experienced thrombotic events. 
      CONCLUSION: Treatment with andexanet alfa rapidly reduced anti-FXa activity with 
      favorable hemostatic efficacy in Japanese patients with acute major bleeding. 
      Serious AEs of thrombotic events during rapid reversal of anti-FXa activity arose 
      as particular safety concerns in this population as with previous studies.
FAU - Toyoda, Kazunori
AU  - Toyoda K
AD  - Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular 
      Center.
FAU - Arakawa, Shuji
AU  - Arakawa S
AD  - Department of Neurology, Steel Memorial Yawata Hospital.
FAU - Ezura, Masayuki
AU  - Ezura M
AD  - National Hospital Organization Sendai Medical Center.
FAU - Kobayashi, Rei
AU  - Kobayashi R
AD  - Department of Neurology, National Hospital Organization Nagoya Medical Center.
FAU - Tanaka, Yoshihide
AU  - Tanaka Y
AD  - Yokosuka Kyosai Hospital.
FAU - Hasegawa, Shu
AU  - Hasegawa S
AD  - Department of Neurosurgery, Japanese Red Cross Kumamoto Hospital.
FAU - Yamashiro, Shigeo
AU  - Yamashiro S
AD  - Division of Neurosurgery, Department of Cerebrovascular Medicine and Surgery, 
      Saiseikai Kumamoto Hospital.
FAU - Komatsu, Yoji
AU  - Komatsu Y
AD  - Department of Neurosurgery, Hitachi General Hospital.
FAU - Terasawa, Yuka
AU  - Terasawa Y
AD  - Brain Attack Center Ota Memorial Hospital.
FAU - Masuno, Tomohiko
AU  - Masuno T
AD  - Nippon Medical School Hospital.
FAU - Kobayashi, Hiroshi
AU  - Kobayashi H
AD  - Research and Development, Alexion, AstraZeneca Rare Disease.
FAU - Oikawa, Suzuko
AU  - Oikawa S
AD  - Research and Development, Bristol Myers Squibb.
FAU - Yasaka, Masahiro
AU  - Yasaka M
AD  - Department of Cerebrovascular Medicine and Neurology, National Hospital 
      Organization Kyushu Medical Center.
LA  - eng
PT  - Journal Article
DEP - 20230826
PL  - Japan
TA  - J Atheroscler Thromb
JT  - Journal of atherosclerosis and thrombosis
JID - 9506298
RN  - 0 (Factor Xa Inhibitors)
RN  - NDU3J18APO (edoxaban)
RN  - 9NDF7JZ4M3 (Rivaroxaban)
RN  - 0 (PRT064445)
RN  - EC 3.4.21.6 (Factor Xa)
RN  - 9000-94-6 (Antithrombin III)
RN  - 0 (Hemostatics)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Anticoagulants)
RN  - 0 (Pyridines)
RN  - 0 (Thiazoles)
SB  - IM
MH  - Humans
MH  - Factor Xa Inhibitors/adverse effects
MH  - Rivaroxaban/adverse effects
MH  - Factor Xa/therapeutic use/pharmacology
MH  - Japan
MH  - Prospective Studies
MH  - Hemorrhage/drug therapy/prevention & control/chemically induced
MH  - Antithrombin III/therapeutic use
MH  - *Hemostatics/therapeutic use
MH  - *Thrombosis/drug therapy
MH  - Fibrinolytic Agents
MH  - Recombinant Proteins/adverse effects
MH  - Anticoagulants/adverse effects
MH  - *Pyridines
MH  - *Thiazoles
PMC - PMC10918051
OTO - NOTNLM
OT  - Anticoagulation
OT  - Antidote
OT  - Asian
OT  - Bleeding
OT  - Intracranial hemorrhage
COIS- Kazunori Toyoda: Personal fees from Daiichi Sankyo, Otsuka, Novartis, Bayer 
      Yakuhin, and Bristol Myers Squibb outside the submitted work. Shuji Arakawa: 
      Personal fees from Daiichi Sankyo and Bayer. Masayuki Ezura: No conflicts of 
      interest. Rei Kobayashi: No conflicts of interest. Yoshihide Tanaka: No conflicts 
      of interest. Shu Hasegawa: No conflicts of interest. Shigeo Yamashiro: No 
      conflicts of interest. Yoji Komatsu: No conflicts of interest. Yuka Terasawa: No 
      conflicts of interest. Tomohiko Masuno: No conflicts of interest. Hiroshi 
      Kobayashi: Employee of Alexion, AstraZeneca Rare Disease. Suzuko Oikawa: No 
      conflicts of interest. Masahiro Yasaka: Lecture fees from Nippon, Boehringer 
      Ingelheim, Bayer, and Daiichi Sankyo.
EDAT- 2023/08/28 00:41
MHDA- 2024/03/05 06:47
PMCR- 2024/03/01
CRDT- 2023/08/27 22:12
PHST- 2024/03/05 06:47 [medline]
PHST- 2023/08/28 00:41 [pubmed]
PHST- 2023/08/27 22:12 [entrez]
PHST- 2024/03/01 00:00 [pmc-release]
AID - DN/JST.JSTAGE/jat/64223 [pii]
AID - 10.5551/jat.64223 [doi]
PST - ppublish
SO  - J Atheroscler Thromb. 2024 Mar 1;31(3):201-213. doi: 10.5551/jat.64223. Epub 2023 
      Aug 26.