Hydralazine Use and Risk of Vasculitis

Importance: Hydralazine is a selectively used cardiovascular medication with case reports and case series demonstrating an association between the use of hydralazine and antineutrophil cytoplasmic antibody-associated vasculitis. Objective: To assess the risk of vasculitis associated with hydralazine use compared with use of an angiotensin-converting enzyme inhibitor (ACE) or angiotensin receptor blocker (ARB). Design, Setting, and Participants: This population-based, retrospective cohort study assessed adults 66 years or older from Ontario, Canada, who were newly prescribed hydralazine from January 1, 2008, to December 31, 2021. Data analysis was performed from May to August 2025. Exposure: Newly dispensed hydralazine in an outpatient setting. Main Outcomes and Measures: The main outcome was a diagnosis of vasculitis using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes. Overlap-weighted Cox proportional hazards regression was used to examine the association between hydralazine use (active comparator: ACE or ARB) with new-onset vasculitis. Results: Of a total of 583 136 eligible adults (mean [SD] age, 73.0 [7.2] years; 51 827 [55.2%] female), 40 748 individuals were dispensed hydralazine and 542 388 an ACE or ARB. Hydralazine use compared with ACE or ARB use was associated with a higher risk of vasculitis during follow-up (hydralazine: 328 events [0.8%]; ACE or ARB: 2712 events [0.5%]; absolute risk difference, 0.3 percentage points; hazard ratio, 1.19; 95% CI, 1.04-1.37). Results were no longer significant when accounting for the competing risk of death. Conclusions and Relevance: In this cohort study of adults who were newly prescribed hydralazine, vasculitis associated with hydralazine was rare, despite multiple reported cases. Use of hydralazine is unlikely to be associated with a clinically meaningful increased risk of vasculitis.