Renin-angiotensin-aldosterone system inhibitors

Last updated: November 6, 2023

Summarytoggle arrow icon

Renin-angiotensin-aldosterone system (RAAS) inhibitors are a group of drugs that act by inhibiting the renin-angiotensin-aldosterone system (RAAS) and include angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin-receptor blockers (ARBs), and direct renin inhibitors. ACE inhibitors and ARBs are commonly used in the treatment of patients with hypertension, heart failure with reduced ejection fraction, and certain types of chronic kidney disease, as well as patients who have had a myocardial infarction. They are particularly important in the treatment of hypertensive diabetic patients, as they prevent the development of diabetic nephropathy. A common side effect of ACE inhibitors is a bradykinin-induced cough, which may necessitate switching to an alternative therapy (e.g., ARBs), while angioedema and hyperkalemia may occur with both ARBs and ACE inhibitor use. Direct renin inhibitors may be considered in hypertensive patients if ACE inhibitors or ARBs are not well tolerated; however, they should never be used in combination with other RAAS inhibitors.

Overviewtoggle arrow icon

The renin-angiotensin-aldosterone system (RAAS)

Types of RAAS inhibitors

Angiotensin-converting enzyme inhibitors (ACE inhibitors)

Angiotensin-receptor blocker (ARBs, sartans)

  • Drug names: valsartan, candesartan, losartan, irbesartan
  • Indications: same as ACE inhibitors, mostly used as second-line treatment if ACE inhibitors are not tolerated
    • Angioedema: can be tried under close surveillance if no adequate alternative is available [5]
    • Non-life-threatening side effects (e.g., dry cough) : commonly used [6]

Angiotensin receptor-neprilysin inhibitors (ARNIs)

  • Drug names: sacubitril/valsartan
  • Indication: Stage C or D HFrEF (preferred initial agent for RAAS inhibition) [7]

Direct renin inhibitors

Pharmacodynamicstoggle arrow icon

ACE inhibitors



Direct renin inhibitors

aLESkiREN: LESS RENin with aliskiren.

Adverse effectstoggle arrow icon

ACE inhibitors

Side effects of CAPTOPRIL: Cough, Angioedema, Pemphigus vulgaris, Teratogenicity, hypOtension, high Potassium, Renal failure, Increased creatinine, Low GFR.



ARNIs have the same contraindications as ACEIs.

Direct renin inhibitors

Acute kidney injury is a potential side effect of all types of RAAS inhibitors, especially in patients with preexisting kidney disease or in combination with NSAIDs

We list the most important adverse effects. The selection is not exhaustive.

Contraindicationstoggle arrow icon

Contraindications for ACE inhibitors and ARBs

Normally, angiotensin II constricts efferent vessels, increasing the GFR. ACE inhibitors antagonize the conversion of angiotensin I to angiotensin II, reducing the GFR.

Contraindications for direct renin inhibitors

We list the most important contraindications. The selection is not exhaustive.

Interactionstoggle arrow icon

ACE inhibitors and ARBs [14]

Direct renin inhibitors [17]

Do not combine direct renin inhibitors with ACE inhibitors or ARBs, especially in patients with diabetes or preexisting kidney disease.

Additional considerationstoggle arrow icon

Referencestoggle arrow icon

  1. Standards of Medical Care in Diabetes 2016. Updated: January 1, 2016. Accessed: February 22, 2017.
  2. Roett MA, Liegl S, Jabbarpour Y. Diabetic nephropathy - the family physician's role. Am Fam Physician. 2012; 85 (9): p.883-889.
  3. Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN. Effect of Enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991; 325 (5): p.293-302.doi: 10.1056/nejm199108013250501 . | Open in Read by QxMD
  4. Franzosi MG, Santoro E, Zuanetti G, et al. Indications for ACE inhibitors in the early treatment of acute myocardial infarction : systematic overview of individual data from 100 000 Patients in randomized trials. Circulation. 1998; 97 (22): p.2202-2212.doi: 10.1161/01.cir.97.22.2202 . | Open in Read by QxMD
  5. Haymore BR, Yoon J, Mikita CP, Klote MM, DeZee KJ. Risk of angioedema with angiotensin receptor blockers in patients with prior angioedema associated with angiotensin-converting enzyme inhibitors: a meta-analysis. Ann Allergy Asthma Immunol .. 2008; 101 (5): p.495-499.doi: 10.1016/s1081-1206(10)60288-8 . | Open in Read by QxMD
  6. Mackay FJ, Pearce GL, Mann RD. Cough and angiotensin II receptor antagonists: cause or confounding?. Br J Clin Pharmacol. 1999; 47 (1): p.111-4.doi: 10.1046/j.1365-2125.1999.00855.x . | Open in Read by QxMD
  7. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2017; 136 (6).doi: 10.1161/cir.0000000000000509 . | Open in Read by QxMD
  8. Karlberg BE. Cough and inhibition of the renin-angiotensin system.. J Hypertens Suppl. 1993; 11 (3): p.S49-52.
  9. Yılmaz İ. Angiotensin-Converting Enzyme Inhibitors Induce Cough.. Turkish thoracic journal. 2019; 20 (1): p.36-42.doi: 10.5152/TurkThoracJ.2018.18014 . | Open in Read by QxMD
  10. Navis G, Faber HJ, de Zeeuw D, de Jong PE. ACE Inhibitors and the Kidney. Drug Saf. 1996; 15 (3): p.200-211.doi: 10.2165/00002018-199615030-00005 . | Open in Read by QxMD
  11. Ayatollahi A, Toossi P, Younespour S, Robati R. Serum angiotensin converting enzyme in pemphigus vulgaris. Indian J Dermatol. 2014; 59 (4): p.348.doi: 10.4103/0019-5154.135478 . | Open in Read by QxMD
  12. Use of angiotensin converting-enzyme inhibitors and angiotensin receptor blockers in CKD. Updated: January 1, 2004. Accessed: April 11, 2018.
  13. Bicket DP. Using ACE inhibitors appropriately. Am Fam Physician. 2002; 66 (3): p.461-469.
  14. Shionoiri H. Pharmacokinetic drug interactions with ACE inhibitors. Clin Pharmacokinet. 1993; 25 (1): p.20-58.doi: 10.2165/00003088-199325010-00003 . | Open in Read by QxMD
  15. Polónia J. Interaction of antihypertensive drugs with anti-inflammatory drugs. Cardiology. 1997; 88 (3): p.47-51.doi: 10.1159/000177507 . | Open in Read by QxMD
  16. Stamp LK, Chapman PT. Gout and its comorbidities: implications for therapy. Rheumatology. 2012; 52 (1): p.34-44.doi: 10.1093/rheumatology/kes211 . | Open in Read by QxMD
  17. Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP. Clinical pharmacokinetics and pharmacodynamics of Aliskiren. Clin Pharmacokinet. 2008; 47 (8): p.515-531.doi: 10.2165/00003088-200847080-00002 . | Open in Read by QxMD
  18. Harel Z, Gilbert C, Wald R, et al. The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis. BMJ. 2012; 344: p.e42.doi: 10.1136/bmj.e42 . | Open in Read by QxMD

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