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New factor Xa inhibitor shows promise
Rivaroxaban is a novel oral direct factor Xa inhibitor which has previously been shown to be effective for the prevention of venous thromboembolism in patients undergoing orthopaedic surgery. The ATLAS ACS-TIMI 46 (Anti-Xa Therapy to Lower cardiovascular events in addition to Aspiron with or without thienopyridine treatment in Subjects with Acute Coronary Syndrome – Thrombolysis In Myocardial Infarction 46) was a double-blind, dose-escalation, phase II study designed to assess the safety and efficacy of rivaroxaban and aimed at selecting the most favourable dose and dosing regimen.
The trial was undertaken at 297 sites in 27 countries. A total of 3491 patients, stabilised after an acute coronary syndrome, were given either aspirin only (n = 761) or aspirin plus a thienopyridine (n = 2730). Participants were then further randomised to receive either placebo or rivaroxaban at doses of 5–20 mg either once daily or the same total dose given twice daily. The primary end point was death, myocardial infarction, stroke or recurrent ischaemia requiring revascularisation within 6 months. A primary safety end point of clinical significant bleeding was also set.
Although no clinically significant difference in the primary end point was found, rivaroxaban reduced the main secondary end point of death, myocardial infarction, or stroke compared with placebo (p = 0.027). The risk of clinically significant bleeding compared with placebo increased in a dose-dependent manner, with a hazard ratio of 2.21 noted for the 5 mg dose, compared with 5.06 for the 20 mg dose.
Rivaroxaban increased bleeding when administered to patients who had had acute coronary syndromes, but a reduction in some clinical end points was also seen—although not in patients receiving dual antiplatelet treatment. A phase III trial is currently under way.
▸ Mega JL, Braunwald E, Mohanavelu S, et al. Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a …