47016
document
Randomised , parallel-group , multicentre , multinational phase 2 study comparing edoxaban , an oral factor Xa inhibitor , with warfarin for stroke prevention in patients with atrial fibrillation . The primary objective of this study was to compare the safety of four fixed-dose regimens of edoxaban with warfarin in patients with non-valvular atrial fibrillation ( AF ) . In this 12-week , parallel-group , multicentre , multinational study , 1,146 patients with AF and risk of stroke were randomised to edoxaban 30 mg qd , 30 mg bid , 60 mg qd , or 60 mg bid or warfarin dose-adjusted to a target international normalised ratio of 2.0-3.0 . The study was double-blind to edoxaban dose , but open-label to warfarin . Primary outcomes were occurrence of major and/or clinically relevant non-major bleeding and elevated hepatic enzymes and/or bilirubin . Mean age was 65 +/- 8.7 years and 64.4 % were warfarin-naïve . Whereas major plus clinically relevant non-major bleeding occurred in 3.2 % of patients randomised to warfarin , the incidence of bleeding was significantly higher with the edoxaban 60 mg bid ( 10.6 % ; p=0.002 ) and 30 mg bid regimens ( 7.8 % ; p=0.029 ) , but not with the edoxaban 60 mg qd ( 3.8 % ) or 30 mg qd regimens ( 3.0 % ) . For the same total daily dose of 60 mg , both bleeding frequency and trough edoxaban concentrations were higher in the 30-mg bid group than in the 60-mg qd group . There were no significant differences in hepatic enzyme elevations or bilirubin values among the groups . The safety profiles of edoxaban 30 and 60 mg qd in patients with AF were similar to warfarin . In contrast , the edoxaban bid regimens were associated with more bleeding than warfarin . These results suggest that in this three-month study , edoxaban 30 or 60 mg qd are safe and well-tolerated .
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Intervention_Pharmacological
edoxaban
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Intervention_Pharmacological
warfarin
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Intervention_Pharmacological
edoxaban with warfarin
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Intervention_Pharmacological
edoxaban
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Intervention_Pharmacological
or warfarin
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Intervention_Pharmacological
edoxaban
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Intervention_Pharmacological
warfarin .
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Outcome_Physical
major and/or clinically relevant non-major bleeding
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Outcome_Physical
elevated hepatic enzymes and/or bilirubin
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Outcome_Physical
relevant non-major bleeding
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Outcome_Physical
the incidence of bleeding
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Outcome_Physical
both bleeding frequency and trough edoxaban concentrations
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Outcome_Physical
in hepatic enzyme elevations or bilirubin values
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Outcome_Physical
more bleeding
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Outcome_Other
are safe and well-tolerated