Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Clinical Outcomes of Off-Label Dosing of Direct Oral Anticoagulant Therapy Among Japanese Patients With Atrial Fibrillation Identified From the SAKURA AF Registry
Nobuhiro MurataYasuo OkumuraKatsuaki YokoyamaNaoya MatsumotoEizo TachibanaKeiichiro KuronumaKoji OiwaMichiaki MatsumotoToshiaki KojimaShoji HanadaKazumiki NomotoKen ArimaFumiyuki TakahashiTomobumi KotaniYukitoshi IkeyaSeiji FukushimaSatoru ItohKunio KondoMasaaki ChikuYasumi OhnoMotoyuki OnikuraAtsushi Hirayamafor the SAKURA AF Registry Investigators
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2019 年 83 巻 4 号 p. 727-735


Background: Off-label dosing of direct oral anticoagulants (DOACs) is encountered clinically among patients with atrial fibrillation (AF), although data on the clinical outcomes of over- and under-dosing are lacking in Japan.

Methods and Results: We examined the clinical outcomes of off-label DOAC dosing using the SAKURA AF Registry, a prospective multicenter registry in Japan. Among 3,237 enrollees, 1,676 under any of the 4 DOAC regimens were followed up for a median of 39.3 months: 746 (45.0%), appropriate standard-dose; 477 (28.7%), appropriate low-dose; 66 (4.0%), over-dose; and 369 (22.2%) under-dose. Compared with the standard-dose group, patients in the under- and over-dose groups were significantly older and had a higher stroke risk. After multivariate adjustment, stroke/systemic embolism (SE) and death events were equivalent between the standard- and under-dose groups, but major bleeding events tended to be lower in the under-dose group (hazard ratio [HR] 0.474, P=0.0739). Composite events (stroke/SE, major bleeding, or death) were higher in the over-dose than in the standard-dose group (HR 2.714, P=0.0081).

Conclusions: Clinical outcomes were not worse for under-dose than for standard-dose users among patients with different backgrounds. Over-dose users, however, were at higher risk for all clinical events and required careful follow-up. Further studies are needed to clarify the safety and effectiveness of off-label DOAC dosing in Japan.

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