Abstract

Hypertension management with antihypertensive (AHT) prescription drugs has been shown to reduce risk of Alzheimer’s disease (AD). The renin-angiotensin system (RAS) has been implicated in AD and may induce differences in protectiveness within RAS-acting AHTs (angiotensin converting enzyme inhibitors (ACEIs), and angiotensin-II receptor blockers (ARBs)) and between RAS-acting and other AHTs (beta blockers, calcium channel blockers, loop diuretics, and thiazide diuretics). We identify the association between AD risk and AHT use, across class, sex, and race/ethnicity. We examined the medical and pharmacy claims of a 20% sample of Medicare beneficiaries from 2007 to 2013, and compared rates of AD diagnosis for 1,347,356 AHT users 65 years of age or older (4,229,259 person-years). We compare RAS-acting AHT users to other AHT users, and ACEI users to ARB users, for black, Hispanic, and non-Hispanic white men and women. RAS-acting AHTs are slightly more protective against onset of AD than non-RAS-acting AHTs for males, but insignificantly different for females (male HR = 0.933 (CI: 0.897-0.971), female HR = 0.983 (CI: 0.961-1.005)). Relative to other AHTs, ARBs are more protective than ACEIs for both sexes (male ACEI HR = 0.982 (CI: 0.943-1.022), female ACEI HR = 1.021 (CI: 0.997-1.047). Male ARB HR = 0.829 (CI: 0.783-0.877), female ARB HR = 0.939 (CI: 0.911-0.967)). The magnitudes of the associations consistently showed better protection for ARBs than ACEIs across race/ethnicity, except for Hispanic females (ACEI HR = 1.010 (CI: 0.924-1.103), ARB HR = 0.995 (CI: 0.899-1.102)). The reduction in AD risk is higher for users of ARBs than other AHTs for most subpopulations, with stronger protection for males than females. Clinical trials that include racial and ethnic groups need to confirm these findings. Physicians should consider potential benefits of some AHTs for reducing AD risk when making prescribing decisions.

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