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

Author:

Morales Jasmine1ORCID,Gabriel Nico2,Natarajan Loki1,LaCroix Andrea Z.1,Shadyab Aladdin H.13,Xu Ronghui145,Silverman James6,Feldman Howard H.67,Hernandez Inmaculada2,

Affiliation:

1. Herbert Wertheim School of Public Health & Human Longevity Science University of California, San Diego La Jolla California USA

2. Division of Clinical Pharmacy Skaggs School of Pharmacy and Pharmaceutical Sciences University of California, San Diego La Jolla California USA

3. Division of Geriatrics, Gerontology, and Palliative Care Department of Medicine University of California, San Diego La Jolla California USA

4. Department of Mathematics University of California, San Diego La Jolla California USA

5. Halicioglu Data Science Institute University of California, San Diego La Jolla California USA

6. Alzheimer's Disease Cooperative Study University of California San Diego, School of Medicine La Jolla California USA

7. Department of Neurosciences University of California, San Diego La Jolla California USA

Abstract

AbstractINTRODUCTIONBumetanide, 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.METHODSWe 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.RESULTSWe 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).DISCUSSIONUsing 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

Wiley

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