Journal Article

Pharmacoepidemiology evaluation of bumetanide as a potential candidate for drug repurposing for Alzheimer's disease

Momper, Jeremiah D., Rizzo, Stacey J. Sukoff, Shadyab, Aladdin H., Hernandez, Inmaculada, Herold, Tatiana, Tanzi, Rudolph E., Lupo, Jody‐Lynn, Galasko, Doug R., Clelland, Claire D., Dodge, Hiroko H., Xu, Ronghui, Silverman, James, Chen, Xu, Nygaard, Haakon B., Rynearson, Kevin D., Herman, Michelle, Pa, Judy, Kaye, Jeffrey, Boyarko, Ben, Koo, Edward H., Greenberg, Barry D., Bowman, Gene L., Gerwick, William H., LaCroix, Andrea Z., Evans, A. Carol, Slusher, Barbara, Yokoyama, Jennifer S., Feldman, Howard H., Edland, Steve D., Bang, Anne, Hook, Vivian, Rexach, Jessica E., Durant, January, Morales, Jasmine, Gabriel, Nico, Bevins, Elizabeth, Kim, Doo Yeon, Quinti, Luisa, Territo, Paul R., Natarajan, Loki, Kosik, Ken S., Messer, Karen, Aslanyan, Vahan, Jacobs, Diane M., Revta, Carolyn, Schneider, Lon, Léger, Gabriel

2024

Overview

INTRODUCTION Bumetanide, a loop diuretic, was identified as a candidate drug for repurposing for Alzheimer's disease (AD) based on its effects on transcriptomic apolipoprotein E signatures. Cross‐sectional analyses of electronic health records suggest that bumetanide is associated with decreased prevalence of AD; however, temporality between bumetanide exposure and AD development has not been established. METHODS We evaluated Medicare claims data using Cox proportional hazards regression to evaluate the association between time‐dependent use of bumetanide and time to first AD diagnosis while controlling for patient characteristics. Multiple sensitivity analyses were conducted to test the robustness of the findings. RESULTS We sampled 833,561 Medicare beneficiaries, 60.8% female, with mean (standard deviation) age of 70.4 (12). Bumetanide use was not significantly associated with AD risk (hazard ratio 1.05; 95% confidence interval, 0.99–1.10). DISCUSSION Using a nationwide dataset and a retrospective cohort study design, we were not able to identify a time‐dependent effect of bumetanide lowering AD risk. Highlights Bumetanide was identified as a candidate for repurposing for Alzheimer's disease (AD). We evaluated the association between bumetanide use and risk of AD. We used Medicare data and accounted for duration of bumetanide use. Bumetanide use was not significantly associated with risk of AD.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Aged / Aged, 80 and over / Alzheimer Disease - drug therapy / Alzheimer Disease - epidemiology / Alzheimer's disease / Antihypertensives / Apolipoproteins / Beneficiaries / Bumetanide - therapeutic use / Candidates / Cohort analysis / Computerized medical records / Cross-Sectional Studies / Dementia / Disease / Diuretics / Drug dosages / Drug Repositioning / drug repurposing / Drugs / FDA approval / Female / Humans / loop diuretics / Male / Medical diagnosis / Medical records / Medicare / Pharmacoepidemiology / Prescription drugs / Proportional Hazards Models / Risk / Robustness / Sodium Potassium Chloride Symporter Inhibitors - therapeutic use / Systematic review / Time / United States - epidemiology / Variables