ARBs Linked to Lower Dementia Risk

9/24/12 8:34 AM

ARBs Linked to Lower Dementia Risk

Download Complimentary Source PDF By Charles Bankhead, Staff Writer, MedPage Today Published: January 13, 2010 Reviewed by Zalman S. Agus, MD; Emeritus Professor University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Older patients treated with an angiotensin receptor blocker (ARB) had a significantly lower risk of dementia and nursing home admission than patients treated with other cardiovascular drugs, data from a large prospective cohort study showed. The incidence of dementia was 20% to 24% lower, and nursing-home admissions were reduced by half among patients on ARBs, Benjamin Wolozin, MD, PhD, of Boston University, and colleagues reported online in BMJ. Results were similar when patients were categorized by dementia or the more specific diagnosis of Alzheimer's disease, suggesting the ARBs' benefits involved more than cardiovascular effects. "It's reasonable to conclude that the ARBs are acting in part by helping with stroke, but I doubt that's the only reason," Wolozin said in an interview. Action Points
Explain to patients that this study showed an association between use of angiotensin receptor blockers and a reduced incidence of Alzheimer's disease and dementia. The findings were based on a retrospective review of patient records and do not prove that treatment with ARBs protects against Alzheimer's disease or dementia.

"We looked at blood-brain barrier penetration, and the ARBs that get into the brain seem to help a little more than the ARBs that don't. That's consistent with what some other people have seen with ACE inhibitors." Several comprehensive summaries have described the role of the renin-angiotensin system (RAS) in Alzheimer's disease and the effects of RAS inhibitors on cognitive function. Moreover, studies have shown associations between ARB therapy and preservation of cognitive function. Preclinical and clinical evidence suggests ARBs help maintain cognitive function by mechanisms unrelated to antihypertensive effects, the authors wrote. But the relative effects of ARBs and angiotensin-converting enzyme (ACE) inhibitors on dementia outcomes had not been studied carefully. To address the issue, Wolozin and colleagues analyzed a Veterans Affairs administrative database covering 2002 to 2006. The analysis included 819,419 patients ages 65 or older with cardiovascular disease. The study population was grouped by type of cardiovascular medication received: ARBs, ACE inhibitors (primarily lisinopril), and other cardiovascular drugs. The primary outcome was time to diagnosis of Alzheimer's disease or dementia. Disease progression was defined as the time to nursing home admission or death among patients with preexisting Alzheimer's disease or dementia. The mean age of the population was about 74, and 98% of the patients were men. The authors reported that 819,491 participants were evaluable for study of Alzheimer's disease and 799,069 for dementia. About 12,000 patients were treated with ARBs, 93,000 with lisinopril, and 714,000 with other cardiovascular drugs. Comparison of Alzheimer's incidence showed a 19% reduction with ARBs versus ACE inhibitors,

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ARBs Linked to Lower Dementia Risk

9/24/12 8:34 AM

including lisinopril, (HR 0.81, 95% CI 0.68 to 0.96, P=0.016) and a 16% reduction versus other cardiovascular drugs (HR 0.84, 95% 0.71 to 1.00, P=0.045). New cases of dementia were 19% lower with ARBs than with lisinopril and other ACE inhibitors (HR 0.81, 95% CI 0.73 to 0.90, P<0.001) and 24% lower than other cardiovascular drugs (HR 0.76, 95% CI 0.69 to 0.84, P<0.001). Among patients with preexisting Alzheimer's disease, treatment with an ARB was associated with a 49% reduction in the rate of nursing home admission (HR 0.51, 95% 0.36 to 0.72, P=0.0001) and a 17% reduction in death (HR 0.83, 95% CI 0.71 to 0.97, P=0.022). The authors found a dose-response effect of ARBs on dementia incidence, as higher doses were associated with lower rates of dementia. The association held true for analysis of individual drugs in the class. Analyses of combination RAS-inhibiting therapy also showed lower rates of Alzheimer's disease, dementia, and nursing home admission among patients treated with an ARB and an ACE inhibitor compared with either class of drug alone. The study was funded by the Retirement Research Foundation and the Casten Foundation. The authors disclosed no relationships aside from those involving the funding sources for the study.

Primary source: BMJ Source reference: Li NC, et al "Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: a prospective cohort analysis" BMJ 2010; 340: b5465.

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