The Comparative Effectiveness of Monotherapy and Combination Therapies: Impact of Angiotensin Receptor Blockers on the Onset of Alzheimer’s Disease - 21/11/24

Doi : 10.14283/jarlife.2023.8 
Y. Wang 1, 2, M. Li 2, 3, L.E. Kazis 4, 5, W. Xia 1, 6, 7,
1 Geriatric Research Education and Clinical Center, Bedford VA Healthcare System, Bedford, MA, USA 
2 Department of Mathematical Sciences, Bentley University, Waltham, MA, USA 
3 Center for Healthcare Organization and Implementation Research, Bedford VA Healthcare System, Bedford, MA, USA 
4 Department of Health Law, Policy and Management, Boston University School of Public Health, Boston, MA, USA 
5 Harvard Medical School and Rehabilitation Outcomes Center (ROC), Spaulding Rehabilitation Hospital, Boston, MA, USA 
6 Department of Pharmacology, Physiology & Biophysics, Boston University School of Medicine, Boston, MA, USA 
7 Department of Biological Sciences, University of Massachusetts, Lowell, MA, USA 

* Corresponding Author: Weiming Xia, Ph.D., Geriatric Research Education and Clinical Center, Bedford VA Healthcare System, 200 Springs Road, Bedford, MA, USA, Telephone 781 824 1077, Fax 781 687 3463 Geriatric Research Education and Clinical Center Bedford VA Healthcare System 200 Springs Road Telephone 781 824 1077 Fax 781 687 3463 Bedford MA USA

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Résumé

Background

The criteria for use of Alzheimer’s disease (AD) drug Leqembi recommended by the Department of Veterans Affairs (VA) include patients aged 65 years or older with mild cognitive impairment (MCI) or mild AD. Comorbidities that include hypertension, hyperlipidemia, and diabetes are common among these patients.

Objectives

Our objective is to investigate the comparative effectiveness of the administration of one, two, or three medications belonging to the categories of angiotensin receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), Beta Blockers, Statins, and Metformin, for their potential to delay the clinical onset of AD and provide a window of opportunity for therapeutic intervention.

Design

Retrospective matched case-control study.

Setting

Data from the Department of Veterans Affairs national corporate data warehouse.

Participants

We conducted an analysis of 122,351 participants (13,611 with AD and 108,740 without AD), aged 65-89, who began at least one of the prescribed medication classes under investigation between October 1998 and April 2018.

Measurements

We utilized Cox proportional hazard regressions, both with and without propensity score weighting, to estimate hazard ratios (HR) associated with the use of different medication combinations for the pre-symptomatic survival time of AD onset. Additionally, we employed a supervised machine learning algorithm (random forest) to assess the relative importance of various therapies in predicting the occurrence of AD.

Result

Adding Metformin to the combination of ACEI+Beta Blocker (HR = 0.56, 95% CI (0.41, 0.77)) reduced the risk of AD onset compared to ACEI monotherapy alone (HR = 0.91, (0.85, 0.98)), Beta Blocker monotherapy (HR = 0.86, 95% CI (0.80, 0.92)), or combined ACEI+Beta Blocker (HR=0.85, 95%CI (0.77, 0.94)), when statin prescribers were used as a reference. Prescriptions of ARB alone or the combination of ARB with Beta Blocker showed an association with a lower risk of AD onset.

Conclusion

Selected medications for the treatment of multiple chronic conditions among elderly individuals with hypertension, hyperlipidemia, and diabetes as monotherapy or combination therapies lengthen the pre-symptomatic period before the onset of AD.

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Mots-clés : Drug repurposing, combination therapy, angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, beta blocker, metformin, statin


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 How to cite this article: Y. Wang, M. Li, L.E. Kazis, et al. The Comparative Effectiveness of Monotherapy and Combination Therapies: Impact of Angiotensin Receptor Blockers on the Onset of Alzheimer’s Disease. J Aging Res & Lifestyle 2023;12:35-45, http://dx.doi.org/10.14283/jarlife.2023.8


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