RAAS Inhibitors | September 2021 | Clinical Corner

September 15, 2021

Renin Angiotensin Aldosterone System Inhibitors (ACE-I and ARB)


ACE cleaves C-terminal peptides on angiotensin I, converting it to angiotensin II, and thus increases blood pressure in two ways: vasoconstriction and stimulation of the release of aldosterone, which increases the retention of water and sodium. ACE-I, ARB’s and DRI’s block this process.

ACE Inhibitors

Angiotensin II Receptor Blockers (ARBs)

benazepril (Lotensin)

candesartan (Atacand)

captopril (Capoten)

eprosartan (Tevetan)

enalapril (Vasotec)

irbesartan (Avapro)

fosinopril (Monopril)

losartan (Cozaar)

lisinopril (Prinivil, Zestril)

olmesartan (Benicar)

perindopril (Aceon)

telmisartan (Micardis)

quinapril (Accupril)

valsartan (Diovan)

ramipril (Altace)

trandolapril (Mavik)

Direct Renin Inhibitor: aliskiren (Tekturna)



  • Experimental and clinical studies have demonstrated RAAS inhibitors prevent proteinuria, kidney fibrosis and slow decline of renal function and thus play a protective role in both early and end stages of kidney disease.
  • No significant benefit for ARB’s and ACE-I used concurrently.
  • RAAS Inhibitors have demonstrated reduction in CV mortality and myocardial infarction, stroke, and heart failure in patients with diabetes.2
  • ACE inhibitors are indicated as an option for initial management of hypertension in patients who are not black, and it is recommended that either an ACE inhibitor or an ARB be prescribed in patients with chronic kidney disease.3
  • The National Institute for Health and Care Excellence recommends ACE inhibitors as first-line therapy for reducing blood pressure in patients with type 2 diabetes, but clinicians may substitute an ARB if the patient cannot tolerate ACE inhibitors (except if there is hyperkalemia or renal dysfunction).4



Considering that angiotensin receptor blockers and ACE inhibitors (ACEIs) are purported to upregulate the expression of ACE2 in animal studies, there may be a concern about whether these drugs may increase COVID-19 susceptibility and severity. ACE inhibitors and ARBs do not act on ACE2, the protein that acts as a SARS-CoV-2 receptor, and treatment with ACE inhibitors or ARBs does not appear to result in increased ACE2 expression.1



  1. Milne S, Yang CX, Timens W, Bossé Y, Sin DD. SARS-CoV-2 receptor ACE2 gene expression and RAAS inhibitors. Lancet Respir Med 2020;8(6):e50-e51
  2. Expert Rev Cardiovasc Ther. 2009 Nov;7(11):1363-71. doi: 10.1586/erc.09.115.
  3. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8) [published correction appears in JAMA. 2014;311(17):1809]. JAMA. 2014;311(5):507–520.
  4. National Institute for Health and Care Excellence. Type 2 diabetes: the management of type 2 diabetes. NICE clinical guideline 87. http://www.nice.org.uk/guidance/cg87/resources/guidance-type-2-diabetes-pdf. Accessed September 15, 2014.