Chemical catalogs of this study showed that all 3 dose regimens of apixaban had an efficacy and safety profile similar to that of the standard therapy, the study investigators concluded that all 3 dosing regimens for apixaban showed similar efficacy and safety to the standard of care therapy. Therefore, they recommended the lowest dosage regimen of 5 mg twice daily to be used in the follow up phase III trials. Currently, there are 2 phase III trials underway, investigating secondary treatment of VTE. The AMPLIFY trial is the follow up trial of the Botticelli DVT trial which involves randomization of patients to either apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily or standard treatment of enoxaparin followed by warfarin for 6 months. Meanwhile, the AMPLIFY EXT trial is investigating apixaban at 2.5 mg or5 mg twice a day for 12 months following usual symptomatic VTE treatment versus placebo. These trials are drug screening libraries estimated to be completed in December 2012. Acute coronary syndrome. APPRAISE 137 trial was a multicenter, double blinded trial. This phase II study investigated the effects of apixaban versus placebo in patients with recent acute coronary syndrome.
These patients were sodium channel randomized to 4 different doses of apixaban or placebo for 6 months. Primary outcomes were major or clinically relevant nonmajor bleeding and secondary outcomes included cardiovascular death, MI, severe recurrent ischemia, or recurrent stroke. Before trial completion, the 2 higher dose apixaban arms were terminated due to excess bleeding, based on the recommendations of the data monitoring committee. Results from this trial demonstrated dose dependent increase in major or clinically relevant bleeding with apixaban compared to placebo. On the contrary, apixaban showed a trend toward a lower rate of ischemic events as compared to placebo. The important findings from subgroup analysis in patients receiving dual antiplatelet therapy with aspirin and clopidogrel showed the risk of bleeding was more peptide synthesis apparent and the reduction in ischemic events was less with higher daily dose of apixaban. In addition, due to the risk benefit assessments of ischemic events and major bleeding, the investigators have selected to use apixaban at a total daily dose of 10 mg for further investigation in a definitive phase III study.
Unfortunately, the APPRAISE 2 trial was terminated early since apixaban did not significantly reduce recurrent ischemic events in patients with an acute coronary syndrome and substantially increased the risk of major bleeding.38 Atrial fibrillation. Currently, phase III studies evaluating apixaban in patients with nonvalvular atrial fibrillation are ongoing. The AVERROES study is a randomized double blind controlled trial evaluating 5 mg twice daily of apixaban versus patient aspirin in patients with atrial fibrillation who are unsuitable to vitamin K antagonist. The ARISTOTLE trial is a randomized, double blind, parallel arm study, evaluating efficacy and safety of apixaban in preventing stroke and systemic embolism in patients with nonvalvular atrial fibrillation by comparing apixaban 5 mg twice daily with standard warfarin therapy. Summary Apixaban is another potent, reversible, and highly selective inhibitor of FXa, similar to rivaroxaban.
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