Angiotensin II Receptor Blockers for brain health

Angiotensin II Receptor Blockers

  • Drugs
  • Updated April 12, 2019

Angiotensin II receptor blockers (ARBs) are a class of prescription drugs (e.g., candesartan, telmisartan) that block the action of angiotensin, a hormone that causes blood vessels to constrict. They are primarily used to manage high blood pressure (hypertension), which, especially in mid-life, is a risk factor for Alzheimer's. Some studies suggest that ARBs may be superior to other antihypertensives in reducing the risk of Alzheimer's or preventing cognitive decline. ARBs are generally safe with few side effects.

Evidence

Observational studies suggest that ARBs may benefit cognition and be superior to other antihypertensives to reduce the risk of Alzheimer's disease, but the evidence is not consistent.

Our search identified:

  • 1 meta-analysis for cognitive function
  • 4 randomized controlled trials for cognitive function
  • 1 meta-analysis of observational studies for risk of Alzheimer's disease
  • 4 observational studies for risk of Alzheimer's disease/dementia
  • 1 randomized controlled trial for risk of MCI and dementia
  • 3 studies on Alzheimer's disease pathology
  • 1 randomized controlled trial in Alzheimer's patients
  • 2 observational studies of Alzheimer's patients on risk of mortality
  • Numerous preclinical studies

Potential Benefit

A meta-analysis and an additional small randomized controlled trial suggested that the use of ARBs may preserve cognition and increase cerebral blood flow more than other antihypertensives in individuals with hypertension [1][2][3]. However, two large randomized controlled trials reported that an ARB had no effect on cognition compared to another antihypertensive or a placebo [4], and one additional trial reported that an ARB only benefitted cognition in individuals with low baseline cognitive function [5].

A meta-analysis of observational studies suggested that ARBs were associated with a reduced risk of Alzheimer's disease and cognitive impairment due to aging [6]. Another observational study suggested that the use of ARBs was associated with a reduced risk of dementia compared to those using another class of antihypertensives called angiotensin converting enzyme (ACE) inhibitors (e.g., lisinopril, perindopril) [7]. Similar results were reported in other observational studies comparing ARBs to other antihypertensives in patients with hypertension and hypertension with type 2 diabetes [8][9]. Finally, another observational study suggested that ARB users performed better on memory tasks than those using other antihypertensives and had fewer white matter hyperintensities, a measure of blood vessel damage in the brain [10].

However, results from the recent SPRINT-MIND trial suggest that intensive blood pressure lowering (<120 vs. <140 systolic blood pressure) may be more important than the choice of blood pressure medication for dementia prevention [11].

Preclinical studies suggest that ARBs may be beneficial in Alzheimer's disease by reducing amyloid plaques, reducing inflammation, and improving blood flow to the brain [12-18].

For Dementia Patients

Two studies showed there may be elevated levels of angiotensin in patients with Alzheimer's disease [19][20]. One small clinical trial in Alzheimer's patients reported that individuals taking an ACE inhibitor had worse cognition over six months while those taking an ARB did not [21]. Other observational studies suggested that individuals with Alzheimer's disease who took ARBs may have a reduced mortality risk compared to those taking other antihypertensives [22][23]. Finally, one study suggested that dementia patients taking ARBs had less biological markers of Alzheimer's after death compared to those taking other antihypertensives [24].

Safety

ARBs are generally safe with side effects similar to a placebo. The most common side effects include headache, respiratory infection, dizziness, and fatigue. Less frequent side effects include hypotension (low blood pressure), kidney failure, and increased potassium levels. They typically have fewer side effects than a similar class of antihypertensives, ACE inhibitors (e.g., lisinopril, perindopril) [25][26].

ARBs increase the absorption of lithium by the kidneys, so the use of lithium with ARBs should be avoided. Dual therapy with ARBs and ACE inhibitors may also increase the risk of hypotension, kidney failure, and increased potassium levels [25][27]. Many drugs interact with ARBs, so concurrent drug use should be discussed with a physician (e.g. telmisartan from Drugs.com).

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

ARBs are available with a prescription and many are available as generic medicines. Starting doses vary depending on the drug (e.g., telmisartan 20-80mg/day, candesartan 8-32mg/day). All ARBs end with the word "sartan." Different classes of antihypertensives are commonly prescribed together and doses are titrated until a target blood pressure is reached.

Learn More

Results from the SPRINT-MIND trial suggested that intensive blood pressure control (systolic blood pressure <120 vs. <140), regardless of the medication, reduced the risk of mild cognitive impairment (MCI) and the combination of MCI and dementia.

Safety and drug interactions can be found at Drugs.com.

Information on new blood pressure guidelines from the American College of Cardiology and the American Heart Association.

Overview of blood pressure medications from the American Stroke Association.

References

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  2. Hajjar I, Hart M, Chen YL et al. (2013) Antihypertensive therapy and cerebral hemodynamics in executive mild cognitive impairment: results of a pilot randomized clinical trial. J Am Geriatr Soc 61, 194-201.
  3. Levi Marpillat N, Macquin-Mavier I, Tropeano AI et al. (2013) Antihypertensive classes, cognitive decline and incidence of dementia: a network meta-analysis. J Hypertens 31, 1073-1082.
  4. Anderson C, Teo K, Gao P et al. (2011) Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies. Lancet Neurol 10, 43-53.
  5. Zanchetti A, Elmfeldt D (2006) Findings and implications of the Study on Cognition and Prognosis in the Elderly (SCOPE) - a review. Blood Press 15, 71-79.
  6. Zhuang S, Wang HF, Li J et al. (2016) Renin-angiotensin system blockade use and risks of cognitive decline and dementia: A meta-analysis. Neurosci Lett 624, 53-61.
  7. Goh KL, Bhaskaran K, Minassian C et al. (2015) Angiotensin receptor blockers and risk of dementia: cohort study in UK Clinical Practice Research Datalink. Br J Clin Pharmacol 79, 337-350.
  8. Davies NM, Kehoe PG, Ben-Shlomo Y et al. (2011) Associations of anti-hypertensive treatments with Alzheimer's disease, vascular dementia, and other dementias. J Alzheimers Dis 26, 699-708.
  9. Kuan YC, Huang KW, Yen DJ et al. (2016) Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers reduced dementia risk in patients with diabetes mellitus and hypertension. Int J Cardiol 220, 462-466.
  10. Ho JK, Nation DA, Alzheimer's Disease Neuroimaging I (2017) Memory is preserved in older adults taking AT1 receptor blockers. Alzheimers Res Ther 9, 33.
  11. Group SMIftSR, Williamson JD, Pajewski NM et al. (2019) Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial. JAMA 321, 553-561.
  12. Kehoe PG (2018) The Coming of Age of the Angiotensin Hypothesis in Alzheimer's Disease: Progress Toward Disease Prevention and Treatment? J Alzheimers Dis 62, 1443-1466.
  13. Torika N, Asraf K, Apte RN et al. (2018) Candesartan ameliorates brain inflammation associated with Alzheimer's disease. CNS Neurosci Ther 24, 231-242.
  14. Torika N, Asraf K, Cohen H et al. (2017) Intranasal telmisartan ameliorates brain pathology in five familial Alzheimer's disease mice. Brain Behav Immun 64, 80-90.
  15. Torika N, Asraf K, Danon A et al. (2016) Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies. PLoS One 11, e0155823.
  16. Trigiani LJ, Royea J, Lacalle-Aurioles M et al. (2018) Pleiotropic Benefits of the Angiotensin Receptor Blocker Candesartan in a Mouse Model of Alzheimer Disease. Hypertension 72, 1217-1226.
  17. Shindo T, Takasaki K, Uchida K et al. (2012) Ameliorative effects of telmisartan on the inflammatory response and impaired spatial memory in a rat model of Alzheimer's disease incorporating additional cerebrovascular disease factors. Biol Pharm Bull 35, 2141-2147.
  18. Tsukuda K, Mogi M, Iwanami J et al. (2009) Cognitive deficit in amyloid-beta-injected mice was improved by pretreatment with a low dose of telmisartan partly because of peroxisome proliferator-activated receptor-gamma activation. Hypertension 54, 782-787.
  19. Savaskan E, Hock C, Olivieri G et al. (2001) Cortical alterations of angiotensin converting enzyme, angiotensin II and AT1 receptor in Alzheimer's dementia. Neurobiol Aging 22, 541-546.
  20. Miners JS, Ashby E, Van Helmond Z et al. (2008) Angiotensin-converting enzyme (ACE) levels and activity in Alzheimer's disease, and relationship of perivascular ACE-1 to cerebral amyloid antipathy. Neuropathol Appl Neurobiol 34, 181-193.
  21. Kume K, Hanyu H, Sakurai H et al. (2012) Effects of telmisartan on cognition and regional cerebral blood flow in hypertensive patients with Alzheimer's disease. Geriatr Gerontol Int 12, 207-214.
  22. Kehoe PG, Davies NM, Martin RM et al. (2013) Associations of angiotensin targeting antihypertensive drugs with mortality and hospitalization in primary care patients with dementia. J Alzheimers Dis 33, 999-1008.
  23. Li NC, Lee A, Whitmer RA et al. (2010) Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ 340, b5465.
  24. Hajjar I, Brown L, Mack WJ et al. (2012) Impact of Angiotensin receptor blockers on Alzheimer disease neuropathology in a large brain autopsy series. Arch Neurol 69, 1632-1638.
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  26. Caldeira D, David C, Sampaio C (2012) Tolerability of angiotensin-receptor blockers in patients with intolerance to angiotensin-converting enzyme inhibitors: a systematic review and meta-analysis. Am J Cardiovasc Drugs 12, 263-277.
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