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Angiotensin 2 Receptor Blocking Agent

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Angiotensin 2 Receptor Blocking Agent, Angiotensin Receptor Blocker, Angiotensin Blocker, Losartan, Cozaar, Irbesartan, Avapro, Candesartan, Atacand, Eprosartan, Teveten, Telmisartan, Micardis, Valsartan, Diovan, Olmesartan, Benicar, Entresto, Exforge, Azor

  • Indications
  1. Intolerance to ACE Inhibitor
  2. See ACE Inhibitor for indications
  • Contraindications
  1. See ACE Inhibitor for contraindications
  2. Angioedema with ACE Inhibitor (relative contraindication)
    1. Bradykinin related reaction that recurs with ARBs in 2% of patients who had Angioedema on ACE Inhibitor
    2. Do not use ARB if ACE inhibitor Induced Angioedema was severe
    3. Precautions given to patient to stop ARB immediately and seak emergency care for signs of Angioedema recurrence
    4. Wait at least 4 weeks between stopping ACE Inhibitor and starting ARB
    5. (2013) J Allergy Clin Immunol 131:1491-3 [PubMed]
  • Preparations
  • ARB alone
  1. Losartan (Cozaar)
    1. Start: 50 mg orally daily or 25 mg daily if volume depleted (MAX 100 mg/day)
    2. Consider twice daily divided dosing
  2. Irbesartan (Avapro)
    1. Start 150 mg orally daily (max 300 mg/day)
  3. Candesartan (Atacand)
    1. Start 8 mg orally daily (maximum 32 mg/day)
  4. Eprosartan (Teveten)
    1. Start 400 mg orally daily (maximum 800 mg/day)
  5. Telmisartan (Micardis)
    1. Start 40 mg orally daily (maximum 80 mg/day)
  6. Valsartan (Diovan)
    1. Start 80 mg orally daily (maximum 320 mg/day)
  7. Olmesartan (Benicar)
    1. Start 20 mg orally daily (maximum 40 mg/day)
  8. Azilsartan (Edarbi)
    1. Start 40 mg orally daily (maximum 80 mg/day)
  • Preparations
  • Combination
  1. Amlodipine (and ARB)
    1. Exforge (Amlodipine and Valsartan)
    2. Azor (Amlodipine and Olmesartan)
  2. Hydrochlorothiazide (and ARB)
    1. Most ARB agents are available in combination with Hydrochlorothiazide (Hctz)
  3. Sacubitril and Valsartan (Entresto)
    1. Indicated in Systolic Dysfunction
    2. Sacubitril (neprilysin inhibitor) increases vasodilation and Sodium excretion
    3. Risk of Hypotension (Number needed to harm 21)
    4. Risk of Angioedema (Number needed to harm 200)
    5. See Systolic Dysfunction for dosing and references
  • Protocol
  • Equivalent dosing (switching between agents)
  1. Losartan (Cozaar) 100 mg daily or divided twice daily
  2. Irbesartan (Avapro) 300 mg daily
  3. Candesartan (Atacand) 16 mg daily
  4. Eprosartan (Teveten) 800 mg daily
  5. Telmisartan (Micardis) 40 mg daily
  6. Valsartan (Diovan) 160 mg daily
  7. Olmesartan (Benicar) 20 mg daily
  8. Azilsartan (Edarbi) 40 mg daily
  • Efficacy
  1. Peak effect may require 4-6 weeks
  2. Proteinuria control is equivalent to ACE Inhibitors
    1. Kunz (2008) Ann Intern Med 148:30-48. [PubMed]
  3. Evidence as of 2015 shows similar efficacy of ARBs as ACE Inhibitors in Myocardial Infarction prevention
    1. (2016) Presc Lett 23(3): 13
  4. Avoid in combination with ACE Inhibitors
    1. No advantage to combinations in Hypertension, vascular disease, Diabetes Mellitus, Coronary Artery Disease
    2. Moderate benefit of combination therapy in Congestive Heart Failure
    3. (2013) Prescr Lett 20(3): 13
  5. Reduce cardiovascular death, Cerebrovascular Accident and Myocardial Infarction risk
    1. Higher level cardiovascular protection than Atenolol
      1. However Atenolol is not the best Beta Blocker for cardiovascular disease prevention
      2. Dahlof (2002) Lancet 359:995-1003 [PubMed]
    2. ARBs do not effect Angiotensin II type 2 receptors
      1. Results in less effect on fibrosis and blood flow
      2. Unlike ACE Inhibitors, ARBs don't effect nitric oxide
      3. (2005) Prescriber's Letter 12:31-2
  • Adverse Effects
  1. Valsartan (Diovan), Irbesartan (Avapro) and Losartan (Cozaar)
    1. N-Nitrosodimethylamine (NMDA) or N-nitrosodiethylamine (NDEA) product contamination (FDA recall 2018)
      1. https://www.fda.gov/Drugs/DrugSafety/ucm613916.htm
      2. https://www.fda.gov/Safety/Recalls/ucm624593.htm
      3. https://www.fda.gov/Safety/Recalls/ucm625492.htm
      4. Product contamination may have been for as long as 4 years
      5. Cancer risk 1 in 8000 patients taking Valsartan for 8 years at 320 mg/day
      6. (2018) Presc Lett 25(9): 49
  2. Olmesartan (Benicar)
    1. Sprue-like Enteropathy
      1. Presents with progressive, severe Chronic Diarrhea, weight loss and sprue-like intestinal changes
      2. May be a delayed Hypersensitivity Reaction (typically months to years after starting Olmesartan)
      3. Rubio-Tapia (2012) Mayo Clin Proc 87(8):732-8 [PubMed]