risk in non-valvular AF (NVAF) patients treated with direct oral anticoagulants (DOAC). Methods Subjects We conducted a single-center prospective observational registry of NVAF patients with DOAC: Safety and effectiveness of 4 Different dIrect oRal anticoagulants, dabigatran, rivaroxaban, apixaban and edoxaban in rEal-world Clinical pracTice (DIRECT registry; UMIN000033283). All serial adult patients (aged ≥18 years) at Osaka Police Hospital with NVAF who were users of dabigatran, rivaroxaban, apixaban, or edoxaban from June 2011 to November 2017 were enrolled. If a patient ever used DOAC during I n daily clinical practice, bleeding risk assessment in patients with atrial fibrillation (AF) is of paramount importance, given that bleeding events in patients with cardiovascular disease can be life-threatening. 1-5 In order to assess the bleeding risk precisely and objectively, we can use the bleeding risk assessment scores, ORBIT or HAS-BLED scores. 2,4,6 The previously reported bleeding risk factors are older age, anemia, bleeding history, insufficient kidney function, treatment with antiplatelets, hypertension, stroke, labile international normalized ratio and so on. 2,4 No factors associated with systemic inflammation have been reported to date. Several studies, however, suggested that systemic inflammation could play a critical role in the subsequent cardiovascular events, 7-9 therefore it is highly possible that activation of systemic inflammatory status could predict subsequent bleeding events. The purpose of the present study was to investigate the impact of systemic inflammation on subsequent bleeding Editorial p 376