Is there Evidence to Support the Use of Direct Factor Xa Inhibitors in Coronary Artery Disease?

Sheila      Anne Doggrell

Abstract

As coronary artery disease (CAD) remains a leading cause of death in the world, the development of anticoagulants 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.

Keywords: Apixaban, clinical pharmacology, clinical trials, coronary artery disease, DX-9065a, preclinical pharmacology, otamixaban, rivaroxaban, ZK-807834