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Renin-angiotensin-aldosterone system inhibitors

Last updated: November 30, 2020

Summary

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 (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, certain types of chronic kidney disease, and patients who have suffered 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 in 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.

Overview

The renin-angiotensin-aldosterone system (RAAS)

Types of RAAS inhibitors

Drug names Indications
ACE inhibitors Enalapril, lisinopril, ramipril, captopril, benazepril
ARBs

Valsartan, candesartan, losartan, irbesartan

Direct renin inhibitors Aliskiren

References:[1][2][3][4][5][6][7][7][8][9]

Pharmacodynamics

Mechanism of action and effect
ACE inhibitors
ARBs (sartans)
Direct renin inhibitors

References:[2][9][10]

Adverse effects

ACE inhibitors

ARBs

  1. Angioedema
  2. Hyperkalemia

Direct renin inhibitors

  1. Rash
  2. Diarrhea

Acute kidney injury is a potential side effect of all types of RAAS inhibitors, especially in patients with pre-existing kidney disease or in combination with NSAIDs!
References:[8][11][12]

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

Contraindications

Contraindications for ACE inhibitors and ARBs

Contraindications for direct renin inhibitors

Normally, angiotensin II constricts efferent vessels and thereby increases the GFR. ACE inhibitors antagonize the conversion of angiotensin I to angiotensin II, thereby reducing the GFR!
References:[2][8][13][14][15][16]

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

Interactions

Do not combine direct renin inhibitors with ACE inhibitors or ARBs, especially in patients with diabetes or pre-existing kidney disease!
References:[17][18][19][20][21]

Additional considerations

References:[2][16]

References

  1. Standards of Medical Care in Diabetes 2016. http://care.diabetesjournals.org/content/suppl/2015/12/21/39.Supplement_1.DC2/2016-Standards-of-Care.pdf. Updated: January 1, 2016. Accessed: February 22, 2017.
  2. Mann JF, Hilgers KF. Renin-Angiotensin System Inhibition in the Treatment of Hypertension. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/renin-angiotensin-system-inhibition-in-the-treatment-of-hypertension.Last updated: July 5, 2016. Accessed: February 22, 2017.
  3. Fischer C. Master the Boards USMLE Step 2 CK. Kaplan Publishing ; 2017
  4. Renin-Angiotensin-Aldosterone System. http://www.cvphysiology.com/Blood%20Pressure/BP015. Updated: August 16, 2012. Accessed: April 11, 2018.
  5. 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
  6. Roett MA, Liegl S, Jabbarpour Y. Diabetic nephropathy - the family physician's role. Am Fam Physician. 2012; 85 (9): p.883-889.
  7. 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
  8. UpToDate. Aliskiren: Drug Information. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/aliskiren-drug-information.Last updated: January 1, 2018. Accessed: April 11, 2018.
  9. Reeder GS. Angiotensin Converting Enzyme Inhibitors and Receptor Blockers in Acute Myocardial Infarction: Clinical Trials. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/angiotensin-converting-enzyme-inhibitors-and-receptor-blockers-in-acute-myocardial-infarction-clinical-trials.Last updated: March 12, 2018. Accessed: April 11, 2018.
  10. Cagnoni F, Njwe CA, Zaninelli A, et al. Blocking the RAAS at different levels: an update on the use of the direct renin inhibitors alone and in combination. Vasc Health Risk Manag. 2010; 6 : p.549-59.
  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. Townsend RR. Major Side Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/major-side-effects-of-angiotensin-converting-enzyme-inhibitors-and-angiotensin-ii-receptor-blockers.Last updated: October 3, 2017. Accessed: April 11, 2018.
  13. Cooper WO, Hernandez-diaz S, Arbogast PG, et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006; 354 (23): p.2443-2451. doi: 10.1056/NEJMoa055202 . | Open in Read by QxMD
  14. August P. Angiotensin Converting Enzyme Inhibitors and Receptor Blockers in Pregnancy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/angiotensin-converting-enzyme-inhibitors-and-receptor-blockers-in-pregnancy.Last updated: January 4, 2017. Accessed: February 22, 2017.
  15. Use of angiotensin converting-enzyme inhibitors and angiotensin receptor blockers in CKD. https://www2.kidney.org/professionals/kdoqi/guidelines_bp/guide_11.htm. Updated: January 1, 2004. Accessed: April 11, 2018.
  16. Bicket DP. Using ACE inhibitors appropriately. Am Fam Physician. 2002; 66 (3): p.461-469.
  17. 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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  19. 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
  20. 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
  21. 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