Pharmacovigilance insights into medication-induced risk of dural arteriovenous fistula

Abstract

Background: Dural arteriovenous fistulas (DAVFs) pose a significant health threat owing to their high misdiagnosis rate. Case reports suggest that DAVFs or related acute events may follow medication use; however, drug-related risk factors remain unclear. In clinical practice, the concomitant use of multiple drugs for therapy is known as "polypharmacy situations," further increasing the risk of drug-induced DAVF. Real-world studies linking medications and DAVF can alert clinicians to their possibilities and contribute to clinical decision-making and patient education.

Method: This study investigated adverse events spanning a decade from the FAERS database, employing pharmacovigilance analysis to systematically assess the risk of drug-induced DAVF. Furthermore, the clinical characteristics of these drug-related DAVFs, such as demographic information, complications, and outcomes, were characterized.

Result: This study generated a broad spectrum of drugs associated with DAVFs. A total of 355 DAVF events, involving 161 drugs across 73 categories, were compiled from millions of records. We identified eight classes of drugs for thorough investigation. Pharmacovigilance analysis revealed that tamoxifen, methylprednisolone, betamethasone, prednisone, rebif, ustekinumab, natalizumab, baclofen, dabigatran etexilate, and bupivacaine have the potential to induce DAVFs. Cerebrovascular thrombotic and embolic events emerge as the most prominent co-adverse events of drug-induced DAVFs. Analyses based on drug-disease targets suggested that the regulation of angiogenesis could be a potential mechanism in tamoxifen-induced DAVFs. Apart from medications with gender-specific prescription patterns, most exhibit a high risk of DAVF in adult male cohorts. Five patients with drug-related DAVFs experienced severe (fatal) outcomes, with four reports attributed to tamoxifen.

Conclusion: These findings highlight the diverse range of drugs implicated in the occurrence or progression of DAVF. Drugs such as tamoxifen, corticosteroids, multiple sclerosis medications, and oral anticoagulants require particular attention. Future research should focus on elucidating the underlying mechanisms and risk factors, such as thrombosis, contributing to drug-induced DAVF to inform preventive strategies and optimize patient care.