Fundam Clin Pharmacol. 2026 Nov;40(6):e70113. doi: 10.1111/fcp.70113.
ABSTRACT
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.
PMID:42893848 | DOI:10.1111/fcp.70113