PMID- 37470020
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230721
IS  - 2575-9108 (Electronic)
IS  - 2575-9108 (Linking)
VI  - 6
IP  - 7
DP  - 2023 Jul 14
TI  - Determination of the Potential Clinical Benefits of Small Molecule Factor XIa 
      Inhibitors in Arterial Thrombosis.
PG  - 970-981
LID - 10.1021/acsptsci.3c00052 [doi]
AB  - Anticoagulants are the mainstay for the prevention and treatment of thrombosis. 
      However, bleeding complications remain a primary concern. Recent advances in 
      understanding the contribution of activated factor XI (FXIa) in arterial 
      thrombosis with a limited impact on hemostasis have led to the development of 
      several FXIa-targeting modalities. Injectable agents including monoclonal 
      antibodies and antisense oligonucleotides against FXIa have been primarily 
      studied in venous thrombosis. The orally active small molecules that specifically 
      inhibit the active site of FXIa are currently being investigated for their 
      antithrombotic activity in both arteries and veins. This review focuses on a 
      discussion of the potential clinical benefits of small molecule FXIa inhibitors, 
      mainly asundexian and milvexian, in arterial thrombosis based on their 
      pharmacological profiles and the compelling results of phase 2 clinical studies. 
      The preclinical and epidemiological basis for the impact of FXIa in hemostasis 
      and arterial thrombosis is also addressed. In recent clinical study results, 
      asundexian appears to reduce ischemic events in patients with myocardial 
      infarction and minor-to-moderate stroke, whereas milvexian possibly provides 
      benefits in patients with minor stroke or high-risk transient ischemic attack 
      (TIA). In addition, asundexian and milvexian had a minor impact on hemostasis 
      even in combination with dual-antiplatelet therapy. Other orally active FXIa 
      inhibitors also produce antithrombotic activity in vivo with low bleeding risk. 
      Therefore, FXIa inhibitors might represent a new class of direct-acting oral 
      anticoagulants (DOACs) for the treatment of thrombosis, although the explicit 
      clinical positions of asundexian and milvexian in patients with ischemic stroke, 
      high-risk TIA, and coronary artery disease require confirmation from the outcomes 
      of ongoing phase 3 trials.
CI  - (c) 2023 The Authors. Published by American Chemical Society.
FAU - Wichaiyo, Surasak
AU  - Wichaiyo S
AUID- ORCID: 0000-0002-1343-7055
AD  - Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok 
      10400, Thailand.
AD  - Centre of Biopharmaceutical Science for Healthy Ageing, Faculty of Pharmacy, 
      Mahidol University, Bangkok 10400, Thailand.
FAU - Parichatikanond, Warisara
AU  - Parichatikanond W
AD  - Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok 
      10400, Thailand.
AD  - Centre of Biopharmaceutical Science for Healthy Ageing, Faculty of Pharmacy, 
      Mahidol University, Bangkok 10400, Thailand.
FAU - Visansirikul, Satsawat
AU  - Visansirikul S
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 
      Bangkok 10400, Thailand.
FAU - Saengklub, Nakkawee
AU  - Saengklub N
AD  - Centre of Biopharmaceutical Science for Healthy Ageing, Faculty of Pharmacy, 
      Mahidol University, Bangkok 10400, Thailand.
AD  - Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok 10400, 
      Thailand.
FAU - Rattanavipanon, Wipharak
AU  - Rattanavipanon W
AD  - Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, 
      Thailand.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230630
PL  - United States
TA  - ACS Pharmacol Transl Sci
JT  - ACS pharmacology & translational science
JID - 101721411
PMC - PMC10353063
COIS- The authors declare no competing financial interest.
EDAT- 2023/07/20 06:42
MHDA- 2023/07/20 06:43
PMCR- 2024/06/30
CRDT- 2023/07/20 04:20
PHST- 2023/03/13 00:00 [received]
PHST- 2024/06/30 00:00 [pmc-release]
PHST- 2023/07/20 06:43 [medline]
PHST- 2023/07/20 06:42 [pubmed]
PHST- 2023/07/20 04:20 [entrez]
AID - 10.1021/acsptsci.3c00052 [doi]
PST - epublish
SO  - ACS Pharmacol Transl Sci. 2023 Jun 30;6(7):970-981. doi: 
      10.1021/acsptsci.3c00052. eCollection 2023 Jul 14.