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[1] 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[2] 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.
Related Chapters
Sources
- The ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction [3]
References
- ↑ Mehta SR, Boden WE, Eikelboom JW, Flather M, Steg PG, Avezum A, Afzal R, Piegas LS, Faxon DP, Widimsky P, Budaj A, Chrolavicius S, Rupprecht HJ, Jolly S, Granger CB, Fox KA, Bassand JP, Yusuf S (2008). "Antithrombotic therapy with fondaparinux in relation to interventional management strategy in patients with ST- and non-ST-segment elevation acute coronary syndromes: an individual patient-level combined analysis of the Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) randomized trials". Circulation. 118 (20): 2038–46. doi:10.1161/CIRCULATIONAHA.108.789479. PMID 18955665. Retrieved 2011-04-11. Unknown parameter
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ignored (help) - ↑ Mehta SR, Granger CB, Eikelboom JW, Bassand JP, Wallentin L, Faxon DP, Peters RJ, Budaj A, Afzal R, Chrolavicius S, Fox KA, Yusuf S (2007). "Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial". Journal of the American College of Cardiology. 50 (18): 1742–51. doi:10.1016/j.jacc.2007.07.042. PMID 17964037. Retrieved 2011-04-11. Unknown parameter
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ignored (help) - ↑ Anderson JL, Adams CD, Antman EM; et al. (2007). "ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine". JACC. 50 (7): e1–e157. PMID 17692738. Text "doi:10.1016/j.jacc.2007.02.013 " ignored (help); Unknown parameter
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