Angiotensin Ii Receptor Antagonist

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Contents 1 More Specific Terms 2 Indications 3 Contraindications 4 Monitor 5 Adverse-effects 6 Drug-interactions 7 Mechanism-of-action 8 More General Terms 9 Additional Terms 10 References

More Specific Terms

• azilsartan (Edarbi)
• candesartan (Atacand)
• eprosartan (Teveten)
• irbesartan (Avapro)
• losartan (Cozaar)
• olmesartan (Benicar)
• telmisartan (Micardis)
• valsartan (Diovan)

Indications

• an ACE inhibitor is indicated, but not tolerated

• heart failure
• diabetes mellitus*
• stroke prevention [2]
• migraine prophylaxis# [4]

• ischemic stroke risk reduction

• diminished risk of cognitive decline likely through diminished risk of ischemic stroke [14]
  

• * No reduction in mortality. [8]
  
• # only candesartan shown to have beneficial effects [4]

Contraindications

• pregnancy, trimesters 2 & 3, probably 1 as well [13]
• angioedema with ACE inhibitor* [3,7]
  

• * 8% of patients with angioedema from ACE inhibitor will experience angioedema with ARB [7]

Monitor

• serum creatinine & serum urea nitrogen every 6 months
• serum electrolytes every 6 months
  
• monitor with ARBs

Adverse-effects

• well tolerated
• similar to placebo
• reduced incidence of cough relative to ACE inhibitors
• urticaria & angioedema (rare)
• increased renal fibrosis? [9]
• no increased risk of myocardial infarction in high-risk patients [11]
• hyperkalemia, may not be a problem with losartan
• increased risk of cancer, RR = 1.1-1.2 [16]
  
• drug adverse effects of angiotensin II receptor antagonists

Drug-interactions

• use in cominbation with beta-blocker & ACE inhibitor is controversial
• ARBs potentiate the effect of diuretics via hypertrophy of the loop of Henle.
  
• drug interaction(s) of renin-angiotensin inhibitors with trimethoprim-sulfamethoxazole
• drug interaction(s) of ACE inhibitors with angiotensin II receptor antagonists
• drug interaction(s) of diuretics with angiotensin II receptor antagonists
• drug interaction(s) of NSAIDs with ARBs
• drug interaction(s) of ACE inhibitors, angiotensin II receptor antagonists & beta-blockers
• drug interaction(s) of NSAIDs, diuretics & angiotensin II receptor antagonists

Mechanism-of-action

• antagonism of angiotensin II receptor type 1 but not type 2 [9]
• comparable to ACE inhibitors in antihypertensive efficacy
• benficial effects on symptoms & hemodynamic/ neurohumoral surrogate markers in patients with heart failure
• antiproteinuric effect; may not prevent microalbuminuria or its progression to proteinuria in diabetic nephropathy
• no inhibitory effect on angiotensin converting enzyme (ACE)
• do not inhibit breakdown of bradykinin
• reduced antihypertensive effect in African Americans (similar to ACE inhibitors)
• may slow progression of atherosclerosis [2]
• may improve insulin sensitivity [10]
• may slow progression to end-stage-renal-disease [12]

More General Terms

• vasodilator agent
• receptor antagonist

Additional Terms

• ACE inhibitors vs angiotensin receptor blockers (ARB)
• angiotensin II
• angiotensin-2 receptor
• angiotensin-converting enzyme [ACE] inhibitor
• CHARM program (clinical trials)
• combination of ACE inhibitor/angiotension 2 receptor antagonist

References

1. Kaiser Permanente Northern California Regional Drug Formulary, Update 9/99
2. Prescriber's Letter 9(4):19 2002
3. Prescriber's Letter 9(11):61 2002
4. Journal Watch 23(4):34, 2003 Tronvik E et al, JAMA 289:65, 2003
5. Prescriber's Letter 10(10):59 2003
6. Journal Watch 23(21):165, 2003
7. Prescriber's Letter 11(7):37 2004
8. Journal Watch 24(23):173, 2004 Strippoli GF, Craig M, Deeks JJ, Schena FP, Craig JC. Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review. BMJ. 2004 Oct 9;329(7470):828. Epub 2004 Sep 30. Review. <PubMed> PMID: [1] <Internet> [2]
9. Prescriber's Letter 12(6): 2005 Comparison of Outcomes Between Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers Detail-Document#: [3] (subscription needed) [4]
10. Prescriber's Letter 12(7): 2005 Evidence for Preventing Type 2 Diabetes Detail-Document#: [5] (subscription needed) [6]
11. Demers C, McMurray JJ, Swedberg K, Pfeffer MA, Granger CB, Olofsson B, McKelvie RS, Ostergren J, Michelson EL, Johansson PA, Wang D, Yusuf S; CHARM Investigators. Impact of candesartan on nonfatal myocardial infarction and cardiovascular death in patients with heart failure. JAMA. 2005 Oct 12;294(14):1794-8. PMID: [7]
    - McDonald MA, Simpson SH, Ezekowitz JA, Gyenes G, Tsuyuki RT. Angiotensin receptor blockers and risk of myocardial infarction: systematic review. BMJ. 2005 Oct 15;331(7521):873. Epub 2005 Sep 23. Review. PMID: [8]
12. Casas JP, Chua W, Loukogeorgakis S, Vallance P, Smeeth L, Hingorani AD, MacAllister RJ. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet. 2005 Dec 10;366(9502):2026-33. Review. PMID: [9]
13. FDA Medwatch [10]
14. Li NC et al Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis BMJ 2010;340:b5465 <PubMed> PMID: [11] <Internet> [12]
15. Prescriber's Letter Comparison of Angiotensin Receptor Blockers Detail-Document#: [13] (subscription needed) [14]
    - Prescriber's Letter 17(3): 2010 CHART: Comparison of Angiotensin Receptor Blockers CHART: Angiotensin Receptor Blocker (ARB) Antihypertensive Dose Comparison CHART: Target Doses of Heart Failure Medications Detail-Document#: [15] (subscription needed) [16]
16. Sipahi I et al Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials Lancet Oncol. 2010 Jul;11(7):627-36. Epub 2010 Jun 11. PMID: [17] doi:10.1016/S1470-2045(10)70106-6 [18]
    - FDA MedWatch, 07/15/2010 Angiotensin Receptor Blockers (ARBs): Ongoing Safety Review for Cancer Risk [19]
17. Prescriber's Letter 18(4): 2011 Comparison of Angiotensin Receptor Blockers Detail-Document#: [20] (subscription needed) [21]
18. National Guideline Clearinghouse Annual monitoring for patients on persistent medications: percentage of health plan members 18 years of age and older who received at least a 180-days supply of ambulatory medication therapy for angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) during the measurement year and at least one serum potassium and either a serum creatinine or a blood urea nitrogen therapeutic monitoring test in the measurement year. National Committee for Quality Assurance ngc-guideline: [22]

angiotensin II receptor antagonist (ARB)