This study aimed to evaluate the label compliance of DOACs in the Chinese AF population and explore the relationship between inappropriate DOACs dosage and clinical results.

This is a retrospective multicenter cohort study conducted in 14 centers in China. According to the China Food and Drug Administration(CFDA) label and the recommendations of international guidelines, we divided patients into on-label dosage and off-label dosage. We then compared the clinical results after propensity score matching. We collect demographic information through the hospital information system and obtain clinical events through follow-up of patients or their families. Clinical results include major, minor, total bleeding, thrombosis, and all-cause death. 4191 patients with non-valvular AF (NVAF) were included, and approximately 55.6% and 1.7% of AF patients received off-label underdose and off-label overdose of DOACs, respectively. Compared with the on-label dose, DOACs with off-label underdose were associated with a significantly reduced risk of major bleeding (P = 0.004, OR = 0.23,95% CI: 0.08–0.69) and all-cause death (P<0.001, OR = 0.49,95% CI: 0.33–0.73). However, there was no significant difference in thrombotic events (P = 0.865 OR = 1.06,95% CI: 0.54–2.07) and minor bleeding (P = 0.465, OR = 1.10,95% CI: 0.85–1.43) risk.

About 57.3% of Asian AF patients received an off-label dose of DOACs in daily practice. Off-label underdose DOACs were associated with significantly lower risks of major bleeding, all-cause death, and similar risks of minor bleeding, thrombotic events compared with on-label dose DOACs. Further prospective randomized trials are needed to determine the optimal dose of DOACs in Asian patients with AF at high bleeding risk.