Unstable angina non ST elevation myocardial infarction factor Xa inhibitors therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-in-Chief: Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Smita Kohli, M.D.

Overview

Factor Xa inhibitors are a class of anticoagulants which act by inhibiting factor Xa, which is a common factor for both the intrinsic and extrinsic pathways of the coagulation cascade.

Factor Xa Inhibitors

Fondaparinux is the prototype in this class of drug which is an indirect Xa inhibitor that requires antithrombin for its action.

Clinical Trial Data

• The OASIS 5 and 6 trials evaluated the use of fondaparinux in ACS and compared it with a heparin-based strategy. Results showed that compared to heparin based strategy, fondaparinux reduced mortality, ischemic events, and major bleeding across the full spectrum of acute coronary syndromes and was associated with a more favorable net clinical outcome in patients undergoing either an invasive or a conservative management strategy.
• The OASIS-5 trial specifically compared fondaparinux, administered at a relatively low dose, 2.5 mg subcutaneously, once daily with standard-dose enoxaparin in 20,078 patients with high-risk UA/NSTEMI. The rates of death, MI, or refractory ischemia throughout the first 9 days were similar with fondaparinux and enoxaparin. Of note, however, the rate of major bleeding was almost 50 percent lower in the fondaparinux arm. By 30 days, mortality was significantly lower in the fondaparinux arm. However, in the subset of patients undergoing PCI, fondaparinux was associated with more than a threefold increased risk of catheter-related thrombi.

Disadvantage of Factor Xa Inhibitors

• Fondaparinux lacks a protamine-binding domain, hence it is not possible to reverse the effect with protamine. In the event of bleeding, discontinuation of their administration and, if needed, transfusion of coagulation factors (e.g., fresh-frozen plasma) is required.