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.
Division of Neurology and Gerontology, Department of Internal Medicine, Iwate Medical University School of Medicine, Iwate, Japan. Electronic address: teray@iwate-med.ac.jp.
Yasuo
Y
Terayama
D000284:Administration, Oral; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects*; D001777:Blood Coagulation / Q000187:drug effects*; D002545:Brain Ischemia / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D000069604:Dabigatran / Q000008:administration & dosage / Q000009:adverse effects*; D016208:Databases, Factual; D017277:Drug Approval; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D020300:Intracranial Hemorrhages / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D000069552:Rivaroxaban / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
D000991:Antithrombins; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran
Cerebrovascular complication; DOAC; PMDA; direct thrombin inhibitor; efficacy and safety; factor Xa inhibitor