Cardiovascular toxicities of hypoxia-inducible factor prolyl hydroxylase inhibitors: a disproportionality analysis based on JADER database

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have shown promising prospects as novel therapeutic agents in renal anemia, but their potential cardiovascular toxicities have raised widespread concern. This study aim to explore the cardiovascular toxicities associated with HIF-PHIs through real-world long-term safety data. A disproportionality analysis was employed by calculating the reporting odds ratios (ROR), information component (IC), and their 95% credibility intervals (CrI) in Japan Adverse Drug Event Report (JADER) database from 1 January 2020, to 30 September 2023. From Q1 2020 to Q3 2023, 253,599 adverse events (AEs) cases were extracted from the JADER database, including 4,015 cases related to HIF-PHIs and 1,537 (38.28%) cases of cardiovascular toxicities. Embolic and thrombotic events (ROR = 6.66, IC = 2.74), cardiac failure (ROR = 3.86, IC = 1.95), and ischemic heart disease (ROR = 3.37, IC = 1.75) indicated positive signals in HIF-PHIs. The median time to onset (TTO) of hypertension for HIF-PHIs was noted to be the earliest at 15.50 days. HIF-PHIs are related to multiple cardiovascular toxicities. Although disproportionality analysis is a hypothesis-driven method, improving the surveillance of these toxicities related to HIF-PHIs used in managing renal anemia is still crucial.