Here's an article on ACE and ARB!
There are angiotensin converting enzyme (ACE) inhibitors drugs and angiotensin receptor blockers (ARB).
Cardiovascular Disorders Ask The Expert
Rationale for Combining ACE Inhibitors and Angiotensin Receptor Blockers
Posted 10/23/2002
from Medscape Primary Care
Question
What is the rationale behind combining angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)?
Stephen George, MD
Response
from Ken Grauer, MD, 10/23/2002
At first glance, one might question the concept of using the combination of an ACE inhibitor and an ARB in the same patient. Both classes of drugs work to inhibit the renin-angiotensin-aldosterone (RAA) system. Combined use would therefore seem redundant.
In actuality, the mechanism of action of ACE inhibitors and ARBs is not exactly the same. Although it is true that the end result of each agent is angiotensin-II inhibition, the site of action of ARBs is more distal than that of ACE inhibitors. ACE inhibitors block the action of the ACE. As a result, angiotensin-I is no longer converted to angiotensin-II. ACE is also responsible for breakdown of bradykinin, which is an inflammatory mediator and vasodilator. ACE inhibition therefore leads to accumulation of bradykinin, which serves to augment the amount of vasodilatation produced by ACE-inhibitor drugs. Just how potent the vasodilatory effect produced by bradykinin will be in any given patient is uncertain. Bradykinin is also important because it may be responsible for the adverse effects of cough and angioedema that occur with ACE inhibitors, but which are rare with ARBs.
In contrast to ACE inhibitors, ARBs do not affect ACE, and therefore do not result in bradykinin accumulation. Instead, ARB drugs produce a more distal (end-receptor blockade) effect that inhibits angiotensin-II. Because enzyme systems other than ACE are involved in angiotensin production, this more distal effect of ARB drugs may actually produce a greater overall angiotensin-II inhibitory effect than ACE inhibitors. However the effect of bradykinin on various vascular beds may counteract the somewhat lesser overall inhibition of angiotensin-II, so that the clinical potency of ACE inhibitors and ARBs for blood pressure reduction is comparable in most studies.
Use of ACE inhibitors is usually preferred initially for treatment of heart failure if there are no contraindications, because of the much greater body of supportive literature on the use of this class of drugs compared with the ARBs. However, when bothersome cough or other idiosyncratic reaction prevents use of ACE inhibitors, substitution of an ARB is usually recommended.
With this background, I offer the following rationale for considering use of both an ACE inhibitor and ARB in the same patient: an augmented clinical effect might be seen in selected patients because the mechanism of action of these 2 classes of drugs, while similar, is not identical. Clinically, combined use is most often contemplated in the treatment of heart failure. Support for this concept was seen in the Val-HeFT Trial, in which the addition of an ARB to either an ACE inhibitor or a beta-blocker had a beneficial effect on morbidity and mortality.[1,2] However, post-hoc analysis of this trial failed to show additional benefit from use of an ARB if both an ACE inhibitor and a beta-blocker were already being used. That stated, it should be remembered that results from evidence-based trials represent statistical likelihood of benefit of a drug (ie, "average effect") in a large population, but does not rule out potential for benefit in an individual patient. In view of Val-HeFT results, however, it is likely that if a patient with chronic heart failure is already on full doses of an ACE inhibitor and a beta-blocker, addition of an ARB will probably not exert a large beneficial effect. However, given our direction as clinicians to individualize patient care in the practice of the "art" of medicine, it is clearly reasonable to consider adding an ARB to the regimen of an individual with heart failure who is already taking an ACE inhibitor and beta-blocker (as well as an optimal diuretic dose and other standard therapy) if he has not optimally responded to previous treatment. This is especially relevant if persistent hypertension remains problematic.
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References
Cohn JN. Cardiology. Improving outcomes in congestive heart failure: Val-HeFT. Valsartan in Heart Failure Trial. 1999;91(suppl 1):19-22.
Cohn JN, Tognoni G, for the Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667-1675.
About the Panel Members
Ken Grauer, MD, Professor of Community Health and Family Medicine and Assistant Director, Family Practice Residency Program, College of Medicine, University of Florida, Gainesville.
Medscape Primary Care 4(2), 2002. © 2002 Medscape
