The Efficacy and Safety of the Off-Label Dose of Direct Oral Anti-Coagulants Treatment in Patients with Atrial Fibrillation in China

Background: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Anti-coagulation therapy, especially direct oral anti-coagulants (DOACs) is an indispensable therapy for AF. Considering the increased risks of bleeding, the off-label dose of DOACs has been applied in East Asia. However, the efficacy and safety of off-label dose of DOACs is controversial. Here, we investigate its efficacy and safety in AF patients in China. Methods: This is a retrospective cohort study. Patients diagnosed with AF between January 2015 and December 2015 were recruited. Participants were divided into three groups according to DOACs dose: standard dose of anti-coagulation (SAG) group, off-label dose of DOACs (OFL) group and non-anti-coagulation (NCG) group. Primary endpoint event was all-cause mortality. Secondary endpoint events included thromboembolic events, acute coronary syndrome, major bleeding and any rehospitalization. All endpoints were collected in 2020. Results: 296 patients were included in this study. All-cause mortality in NCG (52%) group was the highest among these three groups (p<0.001), and there was no significant difference between OFL (14%) and SAG group (19%, p=0.601). Compared to SAG group (1.8%), patients in OFL group (16.2%) had higher risk of stroke and thromboembolic events (p<0.001). The incidence of other events including major bleeding (p=0.597) were similar between SAG group (8.1%) and OFL group (5.4%). Conclusions: Off-label dose of DOACs shows no overall benefits in the occurrence of thromboembolic risk compared to the standard dose of DOACs in AF patients in China. Collectively, standard dose of DOACs should be advocated in China.