AZD0837 is an investigational oral
anticoagulant which is converted to the active form,
AR-H067637, a selective
direct thrombin inhibitor. The present study, a multicentre, randomised, parallel-group, dose-guiding study, assessed the safety and tolerability of an immediate-release formulation of
AZD0837 compared with dose-adjusted
warfarin in the prevention of
stroke and systemic embolic events in
atrial fibrillation (AF) patients. Two hundred fifty AF patients with at least one additional risk factor for
stroke were randomised to receive either immediate-release
AZD0837 (150mg twice daily [bid] or 350mg bid, blinded treatment) or dose-adjusted
warfarin (international normalised ratio 2.0-3.0, open treatment) for three months. The safety and tolerability of 150mg bid
AZD0837 appeared to be as good as that of
warfarin. Total
bleeding events were six with 150mg bid
AZD0837, 15 with 350mg bid
AZD0837 and eight with
warfarin.
Alanine aminotransferase elevations (>3xupper limit of normal) were infrequent, without apparent differences between treatment groups. A numerically higher incidence of serious adverse events was observed with 350mg bid
AZD0837 compared with 150mg bid, with six of 13 being cardiac related, all with different diagnoses. An increase in mean serum
creatinine of approximately 10% was observed in both
AZD0837 groups, which returned to baseline after completion of
therapy. There were no
strokes, transient ischaemic attacks or cerebral haemorrhages with any of the treatments. In conclusion, the safety and tolerability of 150mg bid immediate-release
AZD0837 appeared to be as good as that of dose-adjusted
warfarin. However, larger studies will be needed to define the safety profile of
AZD0837.