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Diabetes, Cardio-Metabolic Newsletter
AACE/ARB
1/6/2014
A new study in older men, has shown that those with testosterone levels in the mid-range had the lowest rates of death from any cause.This
Pharmacotherapy targeting the renin-angiotensin system is one of the most effective means of reducing hypertension and
cardiovascular morbidity. We know that renin is a protease that cleaves angiotensin to produce angiotensin I, which is then
cleaved by angiotensin converting enzyme to angiotensin II. Angiotensin II binds to multiple receptors, with the AT1 and AT2
receptors being the best studied and most abundant in the vasculature. Drugs that selectively inhibit the AT1 receptor are
termed angiotensin receptor blockers.1
There are many evidence based indications for use of ACE inhibitors and ARBs as well as guidelines that recommend
treatment with them for a number of chronic conditions including hypertension, chronic kidney disease with proteinuria, and
heart failure with left ventricular dysfunction. These drugs are commonly prescribed and represent a high percentage of all
prescriptions from primary care in the US and Europe.2In addition to their positive effects on the cardiovascular system, these
agents have been linked to positive outcomes in COPD, pneumonia, primary breast cancer, and dementia.1– 5 A retrospective
study using Veteran’s Affair administrative data found the use of statins and ACE inhibitors prior to admission was associated
with decreased mortality in subjects hospitalized with COPD exacerbations.3 Another population-based case-controlled study
in the UK found that statins and ACE inhibitors were associated with a lower risk of pneumonia. 4 It has been long suspected
that ACE inhibitors and ARBs may have anti-tumor properties as angiotensin II is now regarded as a tumor growth promoter
via angiogenesis from activation of the vascular endothelial growth factor (VEGF) pathway. However, a recent study of 1,449
patients with invasive primary breast cancer published in the Journal of Cancer, found no differences in complete response
rates and survival outcomes between the ACEI/ARB users and non users.5 A 2010 study from the British Medical Journal
found that angiotensin blockers were associated with a significant reduction in the incidence and progression of Alzheimer’s
disease and dementia in a predominantly male population.1Other therapeutic areas where ACE inhibitors and/or ARBs have
shown less than positive results include their effect on abdominal aneurysms and acute kidney injury. A 2006 study using
Canadian administrative data showed that for patients admitted to the hospital with a diagnosis of abdominal aortic aneurysm,
those taking an ACE inhibitor were less likely to present with a ruptured aneurysm. However, a more recent study by Sweeting
et al reported in the Journal of Vascular Surgery found that patients taking ACE inhibitors have faster aneurysm growth,
contrary to the Canadian study results.6A new study by Tomlinson et al published in November 2013, looked at the effect of
ACE inhibitors and ARBs on hospital admissions for patients with acute kidney injury (AKI). AKI is a common problem
implicated in a substantial proportion of hospital admissions with increasing incidence. While AKI has many multifocal
etiologies, one important cause is the use of ACE inhibitors and ARBs. They concluded that up to 15% of the increase in AKI
admissions in England over a 4-year time period is potentially attributable to increased prescribing of ACE inhibitors and
ARBs. The study was limited however, due to a lack of patient level data such as indication for prescribing and patient
characteristics.2It seems most apparent that further research is needed to determine the effects of these valuable drugs
outside of their use in hypertension and cardiovascular disease, and the benefit to risk ratio is as always in the hands of the
practitioner. I DON’T USE IN COMBINATION ANY MORE
References
1. Nien-Chen L, Lee A, Whitmer RA, et al. Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort
analysis. Brit Med Journ. 2010;340:b5465. 2. Tomlinson LA, Abel GA, Chaundhry AN, et al. Ace inhibitor and angiotensin receptor-II antagonist prescribing and
hospital admissions with acute kidney injury: A longitudinal ecological study. PLOS ONE. 2013;8(11)e78465. 3. Mortensen EM, Copeland LA, V Pugh MJ, et al.
Impact of statins and ACE inhibitors on mortality after COPD exacerbations. Resp Res. 2009; Accessed online at Respiratory Research | Full text | Impact of
statins and ACE inhibitors on mortality after COPD exacerbations. 4. Myles PR, Hubbard RB, McKeever TM, et al. Risk of community-acquired pneumonia and the
use of statins, ace inhibitors and gastric acid suppressants: a population-based case-control study. 2009; Accessed online at Risk of community-acquired
pneumonia and the use of statins, ace inhibitors and gastric acid suppressants: a population-based case-control study - Myles - 2009 - Pharmacoepidemiology
and Drug Safety - Wiley Online Library. 5. Young KC, Brown EN, Xiudong L, et al. Use of ACE inhibitors and angiotensin receptor blockers and primary breast
cancer outcomes. J Cancer. 2013;4:549556. 6. Sweeting MJ, Thompson SG, Brown LC, et al. Use of angiotensin converting enzyme inhibitors is associated with
increased growth rate of abdominal aneurysms. J Vasc Surg. 2010;52:1-4.