Drug‐Specific Associations of Angiotensin Receptor Blockers With Parkinson's Disease Risk in a Multicenter Electronic Health Record Cohort

Background Angiotensin receptor blockers (ARBs) have demonstrated neuroprotective effects in preclinical models of Parkinson's disease (PD), but individual ARBs differ in pharmacological properties that may influence their neuroprotective potential. Objectives Using large‐scale hospital electronic health records of the University of California health system, we tested whether specific ARBs are associated with lower PD risk. Methods We conducted a new‐user, active‐comparator cohort study in the University of California Health Data Warehouse, encompassing 890 712 hypertensive patients across six academic medical centers from 2012 to 2025. Cox proportional hazards models estimated hazard ratios for individual ARB associations with incident PD, adjusting for demographics, nine preindex comorbidities, and index date. Robustness was assessed through propensity score matching and negative‐control analysis. Results Drug‐specific Cox analysis identified irbesartan (HR = 0.588, 95% CI 0.434 to 0.796, p = 0.0006) and olmesartan (HR = 0.797, 95% CI 0.665 to 0.956, p = 0.015) as associated with lower PD risk. Irbesartan survived Bonferroni correction for multiple comparisons, and propensity score matching supported both associations. Conclusion In this large multicenter EHR cohort, irbesartan and olmesartan were associated with lower incident Parkinson's disease risk. These findings support further investigation of the renin‐angiotensin system as a therapeutic target in Parkinson's disease and may inform the development or repurposing of agents with favorable central nervous system penetration and neuroprotective potential.