Off-label dose direct oral anticoagulants and clinical outcomes in Asian patients with atrial fibrillation: A new evidence of Asian dose

Aim 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. Methods and 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. Conclusions 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.