Evaluation of the Efficacy and Safety of Direct Oral Anticoagulants in Japanese Patients-Analysis of Pharmaceuticals and Medical Devices Agency Data.

BACKGROUND: Two forms of direct oral anticoagulant (DOAC) have recently been introduced: direct thrombin inhibitors (DTI; e.g., dabigatran) and factor Xa inhibitors (FXa; e.g., rivaroxaban and apixaban). Despite the advantages of DOACs over warfarin with regard to cerebrovascular complications, those associated with DOACs have been reported with the increasing use of DOACs. Nevertheless, little is known about real-world comparative efficacy and safety of DOACs.

METHODS: Cerebrovascular adverse events collected by the Pharmaceutical and Medical Devices Agency (PMDA) during 2014 were analyzed to describe and compare efficacy and safety among patients prescribed DTI and FXa.

RESULTS: Thirty-six cerebrovascular events associated with DTI and 419 events with FXa were reported during 2014. Ratios of hemorrhagic to ischemic events were similar in both DTI (2.2) and FXa (1.9) groups, with hemorrhagic events exceeding ischemic events. Ratios of intracerebral hemorrhage to total hemorrhagic events in patients with FXa (0.84) were significantly higher than those taking DTI (0.48; P < .01), but ratios of subdural (epidural) hemorrhage in FXa (0.14) were significantly lower than in DTI (0.44; P < .01). Among patients developing cerebral infarction, ratios of embolic to total ischemic events among FXa (0.34) and DTI (0.31) were comparable, but no patients taking DTI developed atherothrombotic infarction, compared with patients taking FXa (ratio of atherothrombotic to total ischemic events = 0.15).

CONCLUSIONS: The present study indicates that different drug effects on cerebrovascular events may exist between DTI and FXa. DTI may play important roles in reducing and preventing intracerebral hemorrhage and atherothrombotic events.