Trusted medical expertise in seconds.

Access 1,000+ clinical and preclinical articles. Find answers fast with the high-powered search feature and clinical tools.

Try free for 5 days
Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer.

Renin-angiotensin-aldosterone system inhibitors

Last updated: September 19, 2021

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.

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

Direct renin inhibitors

ACE inhibitors


Direct renin inhibitors

aLESkiREN: LESS RENin with aliskiren.

ACE inhibitors

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


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.

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.

ACE inhibitors and ARBs [12]

Direct renin inhibitors [15]

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

  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. Karlberg BE. Cough and inhibition of the renin-angiotensin system.. J Hypertens Suppl. 1993; 11 (3): p.S49-52.
  7. 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
  8. 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
  9. 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
  10. Use of angiotensin converting-enzyme inhibitors and angiotensin receptor blockers in CKD. Updated: January 1, 2004. Accessed: April 11, 2018.
  11. Bicket DP. Using ACE inhibitors appropriately. Am Fam Physician. 2002; 66 (3): p.461-469.
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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