Angiotensin II receptor antagonist

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In pharmacology, Angiotensin II receptor antagonists, also called Angiotensin II Type 1 receptor blockers ('ARBs) are "agents that antagonize angiotensin II type 1 receptor. Included are angiotensin II analogs such as saralasin and biphenylimidazoles such as losartan. Some are used as antihypertensive agents."[1]

Inhibition of the renin-angiotensin system is used to treat hypertension, heart failure, and chronic kidney disease.

Mechanism of action

Angiotensin II receptor antagonists block angiotensin II AT1 receptors, in contrast to angiotensin-converting enzyme inhibitors, which block the conversion of angiotensin I to the hypertensive angiotensin II. Along with Angiotensin-converting enzyme inhibitors. Randomized controlled trials have investigated the use of the two classes together for a synergistic effect, but have found increased adverse effects with no added benefit from their combination.[2]

Applications

Hypertension

A meta-analysis by the Cochrane Collaboration concluded:[3]

  • The blood pressure "lowering effect of ARBs is modest and similar to ACE inhibitors as a class; the magnitude of average trough BP lowering for ARBs at maximum recommended doses and above is -8/-5 mmHg. Furthermore, 60 to 70% of this trough BP lowering effect occurs with recommended starting doses."
  • "There are no clinically meaningful BP lowering differences between available ARBs."

Heart failure

Two meta-analyses have review the role of adding ARBs to ACE inhibitors:

  • "ARBs should not routinely be added to ACEI therapy for left ventricular dysfunction."[4]
  • "Combination ARB plus ACE inhibitor therapy in subjects with symptomatic left ventricular dysfunction was accompanied by marked increases in adverse effects."[5]

Clinical practice guidelines state:

  • 2011 The National Institute for Health and Clinical Excellence[6]
    • Consider adding an ARB, but the guideline lists the option of adding an aldosterone antagonist first
  • 2008 European Society of Cardiology:[6]
    • "Unless contraindicated or not tolerated, an ARB is recommended in patients with HF and an LVEF ≤40% who remain symptomatic despite optimal treatment with an ACEI and β-blocker, unless also taking an aldosterone antagonist."
  • 2009 update of ACC/AHA guidelines:[7]
    • "Addition of an aldosterone antagonist is recommended in selected patients with moderately severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal function and normal potassium concentration. Creatinine should be 2.5 mg per dL or less in men or 2.0 mg per dL or less in women and potassium should be less than 5.0 mEq per liter."
    • "potassium should be reassessed within 1 to 2 weeks after initiation and followed closely after changes in dose"

Chronic kidney disease

ARBs may also be used to protect the kidneys.

Adverse effects

Hyperkalemia

Angiotensin II receptor antagonists can cause hyperkalemia. The rise in potassium has been reported to be both similar to[8] and less that occurs with angiotensin-converting enzyme inhibitors.[9] A newer factorial randomized controlled trial has compared these drugs.[10]

Angioedema

Patients who previously had angioedema (a hypersensitivity reaction) with angiotensin-converting enzyme inhibitors may be at increased risk of angioedema with angiotensin II receptor antagonists.[11]

Cancer

ARBs may increase the rate of cancer.[12]

References

  1. Anonymous (2015), Angiotensin II Type 1 Receptor Blockers (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. McMurray JJ (April 2008). "ACE inhibitors in cardiovascular disease--unbeatable?". N. Engl. J. Med. 358 (15): 1615–6. DOI:10.1056/NEJMe0801925. PMID 18378521. Research Blogging.
  3. Heran BS, Wong MM, Heran IK, Wright JM (2008). "Blood pressure lowering efficacy of angiotensin receptor blockers for primary hypertension". Cochrane database of systematic reviews (Online) (4): CD003822. DOI:10.1002/14651858.CD003822.pub2. PMID 18843650. Research Blogging.
  4. Lakhdar R, Al-Mallah MH, Lanfear DE (2008). "Safety and tolerability of angiotensin-converting enzyme inhibitor versus the combination of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker in patients with left ventricular dysfunction: a systematic review and meta-analysis of randomized controlled trials.". J Card Fail 14 (3): 181-8. DOI:10.1016/j.cardfail.2007.11.008. PMID 18381180. Research Blogging.
  5. Phillips CO, Kashani A, Ko DK, Francis G, Krumholz HM (2007). "Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials.". Arch Intern Med 167 (18): 1930-6. DOI:10.1001/archinte.167.18.1930. PMID 17923591. Research Blogging. Review in: ACP J Club. 2008 Mar-Apr;148(2):35
  6. 6.0 6.1 Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA et al. (2008). "ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).". Eur Heart J 29 (19): 2388-442. DOI:10.1093/eurheartj/ehn309. PMID 18799522. Research Blogging.
  7. Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG et al. (2009). "2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation.". J Am Coll Cardiol 53 (15): e1-e90. DOI:10.1016/j.jacc.2008.11.013. PMID 19358937. Research Blogging.
  8. The ONTARGET Investigators. 2008. Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events. N Engl J Med 358, no. 15:1547-1559.
  9. Bakris GL, Siomos M, Richardson D, et al (2000). "ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. VAL-K Study Group". Kidney Int. 58 (5): 2084–92. DOI:10.1111/j.1523-1755.2000.00381.x. PMID 11044229. Research Blogging.
  10. Mann et al. 2008. Lancet. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial
  11. Haymore BR, Yoon J, Mikita CP, et al. 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 November;101:495-9.
  12. Sipahi I, Debanne SM, Rowland DY, Simon DI, Fang JC (2010). "Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials.". Lancet Oncol 11 (7): 627-36. DOI:10.1016/S1470-2045(10)70106-6. PMID 20542468. Research Blogging.