Is there evidence to support the use of direct Factor Xa inhibitors in coronary artery disease?
As coronary artery disease (CAD) remains a leading cause of death in the world, the development of anti-coagulants to prevent CAD progressing to myocardial infarction and death is a high priority. A number of direct Factor Xa (FXa) inhibitors are being developed for use in CAD. Despite being developed to the stage of Phase II clinical trials, DX-9065a is no longer a priority with its developing company for further development, possibly because the Phase II trials did not show any major benefit of DX-9065a over heparin in subjects undergoing percutaneous coronary interventions (PCI) or with non-ST-elevation acute coronary syndromes (ACS). ZK-807834, otamixaban, apixaban, and rivaroxaban are all direct FXa inhibitors that have undergone preclinical and some clinical testing for use in CAD. In a large Phase II clinical trial of subjects with ACS, some doses of otamixaban had a better benefit/risk profile than the unfractionated heparin/eptifibatide combination. However, neither ZK-807834 nor otamixaban appear to be undergoing further clinical development at present. In ACS, placebo-controlled large Phase II clinical trials with apixaban and rivaroxaban have not shown clear cut benefits. Nevertheless, apixaban and rivaroxaban are presently in placebo-controlled Phase III clinical trials for ACS. Presently, there is no compelling evidence to support the use of direct FXa inhibitors in ACS.
Discipline of Medical Sciences, Faculty of Science and Technology, Queensland University of Technology, GPO 2343, QLD 4001, Brisbane, Australia. sheila.doggrell@qut.edu.au
Sheila Anne
SA
Doggrell
D000578:Amidines / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000188:drug therapy*; D003497:Cyclic N-Oxides / Q000627:therapeutic use; D015951:Factor Xa / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors; D006801:Humans; D009025:Morpholines / Q000627:therapeutic use; D009281:Naphthalenes / Q000627:therapeutic use; D011422:Propionates / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D000069552:Rivaroxaban; D013876:Thiophenes / Q000627:therapeutic use
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D000578:Amidines; D003497:Cyclic N-Oxides; D065427:Factor Xa Inhibitors; D009025:Morpholines; D009281:Naphthalenes; D011422:Propionates; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013876:Thiophenes; C114592:Fidexaban; C522181:apixaban; D000069552:Rivaroxaban; D015951:Factor Xa; C435830:otamixaban