HIF-PHIs associated with embolic and thrombotic events: a real-world pharmacovigilance study based on the Japan Adverse Drug Event Report database.

Background: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) play an important role in the treatment of renal anemia. However, some studies suggest a potential link between HIF-PHIs and increased thrombosis risk, though these findings are inconsistent and lack large-scale clinical support. We aim to summarize embolic and thrombotic events associated with HIF-PHIs in different populations in real world, especially among high-risk patients.

Methods: Using the Japan Adverse Drug Event Report (JADER) database from January 1, 2020, to September 30, 2023, a disproportionality analysis was employed to identify embolic and thrombotic events associated with HIF-PHIs using the reporting odds ratios (ROR) and information component (IC). We also evaluated the time to onset among different populations.

Results: From January 2020 to September 2023, the JADER database reported a total of 253,599 cases, including 1,222 cases of embolic and thrombotic events, which represented 30.44% of all HIF-PHIs reported. Embolic and thrombotic events (ROR = 6.68) related to HIF-PHIs is positive signal, with the strongest signal observed for vessel type unspecified and mixed arterial and venous (ROR = 7.97). The signal intensity is higher in females than in males (p = 0.008) and also greater in the non-dialysis population compared to the dialysis population (p < 0.001). The median onset time was shorter in the dialysis population than in the non-dialysis population (days: 27 vs. 47, p = 0.016).

Conclusion: Attention to embolic and thrombotic events associated with HIF-PHIs is essential, with careful selection of specific types based on underlying diseases, sex, age, and indications.