Angiotensin II Receptor Blockers

The Angiotensin II Receptor Blockers (ARBs) are a newer class of drugs being studied and sometimes used to treat Coronary Heart Disease (CHD). Angiotensin II is a hormone released into the blood which causes the blood vessels to constrict (or tighten or close). When blood vessels constrict, it makes it difficult for the heart to pump blood through them. ARBs block Angiotensin II from binding to its receptors allowing the blood vessels to relax and dilate (or open), lowering blood pressure and reducing how hard the heart has to work to pump blood.

Currently ACE-Inhibitors are often used as the first-line therapy to treat CHD. The effects of ACE-Inhibitors and ARBs are similar given that both classes block Angiotensin II as their primary action. This has led investigation into the possible role of ARBs in the treatment of CHD, especially because some individuals cannot tolerate ACE-Inhibitors. Additionally, ARBs may provide more complete suppression of angiotensin II.

Drugs in this Class
Telmisartan (Micardis)
Olmesartan Tablets (Benicar Tablets, Olmesartan Medoxomil Tablets)
Irbesartan (Avapro)
Valsartan (Diovan)
Candesartan (Atacand)
Losartan (Cozaar)
Eprosartan Tablets (Eprosartan Mesylate Tablets, Teveten Tablets)

Summarizing the Evidence

  • Currently, no large, head-to-head, randomized controlled trials have been published that compare the ARBs to each other for the treatment of CHD. However, some ARBs have been compared to other CHD therapies (mainly the ACE-inhibitors) for the treatment of CHD.

  • Based on the results of a large randomized, controlled study, called the Valsartan, Captopril, or Both in Myocardial Infarction Complicated by Heart Failure, Left Ventricular Dysfunction, or Both (VALIANT) trial, valsartan was shown to be just as effective as the first-line agent ACE-inhibitors (such as captopril) in the reduction of death, further heart attacks, strokes, and other cardiovascular (heart-related) events. While the study showed that valsartan is just as effective as captopril, it also showed that the combination of the two agents together does not produce additional reductions in death or cardiovascular events.

  • The Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan (OPTIMAAL) trial, a large randomized controlled trial, compared the use of losartan to captopril (an ACE-inhibitor) to prove that losartan was either just as good as or better than captopril for reducing death and additional heart-related events after a heart attack. The study investigators found no difference in the number of deaths from heart attack, stroke, or other cardiovascular causes, nor was there a difference between the losartan and captopril groups in the number of second heart attacks or hospital admissions. It also found that patients were more likely to continue taking losartan than captopril because losartan does not cause as many side effects as captopril.

  • A small study performed in Japan looked at the effects of candesartan on the prevention of heart attack and death from cardiovascular events in patients who have CHD. This study showed that addition of candesartan to current CHD therapy decreased the risk of heart attack and death due to cardiovascular reasons. When the treatment groups were broken down to see if any significant differences existed based on the other CHD therapies participants were on, the findings were similar to those of other studies in that addition of candesartan to standard therapy including an ACE-inhibitor showed no additional decrease in risk of events.

  • The Val-PREST trial, was a small study conducted in 200 patients who had cardiac stents (a short narrow metal or plastic tube that is inserted into a blocked blood vessel in the heart to keep the blood vessel open). The study compared valsartan to placebo in terms of ability to maintain stent functionality. The Val-PREST study showed that fewer patients required replacement of their stents after 6 months of receiving valsartan as compared to placebo. Additionally, in those patients who did not need a new stent placed during the study, their arteries were not as narrowed in the valsartan group as compared to those in the placebo group.

  • Given the information currently available, ARBs are most likely as effective as ACE-I, but should only be considered second line therapy in those patients who are unable to tolerate ACE-I. Also when you take into consideration cost, ARBs are a more expensive treatment option as they are only available in brand name (no generic is available).

Dosing and Administration

*Exact dosing can only be determined for valsartan as it is currently the only FDA-approved ARB for the treatment of CHD. Doses for the other ARBs listed are general doses currently used in hypertension.

  • Valsartan is usually taken two times a day after an individual has experienced a heart attack.

  • Irbesartan, olmesartan, and telmisartan are all generally taken once a day.

  • Candesartan, eprosartan, and losartan can all be taken once or twice a day.

Generic Availability

  • No drugs in this class are currently available in generic formulations.

  • Losartan (brand name: Cozaar) is the oldest ARB and will most likely be the first drug in this class to become available generically. The patent is expected to expire in late 2010; however, there is no guarantee as to exactly when this will happen or how long it will take before a generic formulation is approved.

Drug Interactions

Some interactions between medications can be more severe than others. The best way for you to avoid harmful interactions is to tell your doctor and/or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals. For specific information on how the drugs interact and the severity of the interaction, please use our Drug Interactions Checker.

Side Effects

To view specific side effect information, please use our Side Effect Checker.

Additional Information
References

  1. Cozaar [package insert]. Whitehouse Station, NJ: Merck & Co, Inc.; December 2005.
  2. Diovan [package insert]. East Hanover, NJ: Novartis Pharmaceutical Co; June 2007.
  3. Avapro [package insert]. New York, NY: Sanofi-Synthelabo; October 2005.
  4. Atacand [package insert]. Wilmington, DE: AstraZeneca; February 2007.
  5. Micardis [package insert]. Ridgefield, CT: Boehringer Ingelheim; May 25, 2006.
  6. Teveten [package insert]. Morrisville, NC: Biovail Pharmaceuticals; September 2005.
  7. Benicar [package insert]. New York, NY: Sankyo Pharmaceuticals. October 2006.
  8. Hyzaar [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; December 2005.
  9. Pfeffer MA, McMurray JJV, et al. Valsartan, Captopril, or Both in Myocardial Infarction Complicated by Heart Failure, Left Ventricular Dysfunction, or Both (VALIANT) trial. New England Journal of Medicine. 2003;349(20):1893-1906.
  10. Dunlap ME. New Studies Influencing Treatment of Heart Failure: 2006 update. Pharmacotherapy Supplement. 2007; 27: 3S-11S.
  11. Dickstein K, Kjekshus J, and the OPTIMAAL steering committee. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomized trial. The Lancet 2002; 360 752-60.
  12. Kondo J, Sone T, et al. Effects of low-dose angiotensin II receptor blocker candesartan on cardiovascular events in patients with coronary artery disease. American Heart Journal. 2003 Dec; 146(6):1-6.
  13. Talbert RL. Ischemic Heart Disease. In: Dipiro JT, Talbert RL, Yee GC et.al (Eds). Pharmacotherapy: a pathophyisologic approach. 6th ed. New York: McGraw-Hill, 2005:261-290.
  14. Lithell H, Hansson L, Skoog I, et al. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. Journal of Hypertension 2003 Feb 20; 21: 875-86.
  15. Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomized trial. Lancet 2007 Jun 19; 363: 2022-31.
  16. Peters S, Gotting B, Trummel M, et al. Valsartan for Prevention of Restenosis After Stenting of Type B2/C Lesions: The Val-PREST trial. Journal of Invasive Cardiology 2001 Feb; 13(2): 93-97.
  17. Krumholz HM, Anderson JL, Brooks NH, et al. ACC/AHA Clinical Performance Measures for Adults With ST-Elevation and Non ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/ American Heart Association Task Force on Performance Measures. Journal of American College of Cardiology 2006; 47: 236-65.

Last Updated: April 2008

Note: The above information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist, or other healthcare professional. It should not be construed to indicate that the use of the product is safe, appropriate, or effective for you. Consult your healthcare professional before taking any medication.

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