Trend of Reported Bleeding in Warfarin Compared with Direct Oral Anticoagulants in Japan

Evidence on bleeding events associated with oral anticoagulants in real-world settings is limited. Thus, we compared the incidence rate of oral anticoagulant-associated bleeding between warfarin and direct oral anticoagulants (DOACs).

This is a retrospective observational study using the Japanese Adverse Drug Event Report Database (JADER) and the nationwide health insurance claims database. We investigated the number of case reports with "bleeding" or "hemorrhage" using the JADER. The drugs of interest included warfarin, dabigatran, edoxaban, rivaroxaban, or apixaban. Main outcome measures included the number of case reports of bleeding and the estimated annual incidence rate of oral anticoagulant-associated bleeding using the Japanese Adverse Drug Event Report (JADER) and the nationwide estimated number of patients with prescriptions.

In JADER, we found 16,125 oral anticoagulant-associated bleeding in 15,970 case reports of patients between April 1, 2004, and March 31, 2024. The most common suspected oral anticoagulant administered to patients was apixaban (33.4%), followed by rivaroxaban (26.0%), warfarin (16.6%), edoxaban (13.3%), and dabigatran (10.7%). The incidence rates of anticoagulant-associated bleeding in patients who were prescribed dabigatran, edoxaban, rivaroxaban, and apixaban were higher compared to those in patients who were prescribed warfarin. The estimated annual incidence rate was remarkably high in patients who received apixaban, reaching 1976.90 per 1,000,000 patients.

Compared with warfarin, the incidence rates of oral anticoagulant-associated bleeding were higher with dabigatran, edoxaban, rivaroxaban, or apixaban. In a real-world setting in Japan, the risk of oral anticoagulant-associated bleeding appears to be higher with DOACs than with warfarin.