Henry R. Black, MD; Domenic A. Sica, MD


July 20, 2012

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Henry R. Black, MD: Hi. I'm Dr. Henry Black. I'm Clinical Professor of Internal Medicine at the New York University School of Medicine, past President of the American Society of Hypertension, and a member of the Center for the Prevention of Cardiovascular Disease at New York University. I'm here today with my friend and colleague, Dr. Domenic Sica. Dom?

Domenic A. Sica, MD: Hello. I'm Dr. Domenic Sica, Professor of Medicine and Pharmacology and Eminent Scholar at Virginia Commonwealth University Health System in the fine city of Richmond.

Dr. Black: One of the things that Dom and I have talked and written about is the comparison between angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors. One particular concern is the tolerability of ARBs and whether they cause angioedema. In my opinion, they don't, and that is what we have written. What do you think?

Dr. Sica: It is a little bit of an elusive target. We know that ACE inhibitors cause angioedema of varying severity. It is somewhat more common in women than in men and much more common in African Americans and blacks in general than in Caucasians. It may be about 2-3 times higher in women than men. The ARB storyline is interesting because when angioedema occurred with ACE inhibitors and people were challenged with an ARB, presuming that a renin-angiotensin system blocker was going to be used, a small portion of patients developed angioedema of lesser severity.

Dr. Black: Can you predict which patients will have this?

Dr. Sica: No. There is no phenotypic characteristic that you can rely on, but if you had a past episode, you were more likely to get it. However, people got it de novo when just starting an ARB.

Dr. Black: But angioedema happens to a large percentage of the population.

Dr. Sica: Yes, and that takes us to the heart of the matter, which is that sometimes it is difficult to determine what is background noise for angioedema versus a causality. We do know that people who have angioedema with an ACE inhibitor are more likely to get it with an ARB if they are to get it with an ARB, but you cannot neglect the fact that you can still have just background angioedema that doesn't relate per se. I just saw a patient who carried an ACE inhibitor angioedema label who was a high renin hypertensive. He needed something. They were afraid to give him an ARB. They were afraid to give him aliskiren. In reality, after I delved into the case as a new patient, it turned out that he had aspirin-related angioedema. We were able to rechallenge him with an ACE inhibitor with no problem.

Dr. Black: Are you concerned about giving an ARB to someone who had angioedema from an ACE inhibitor?

Dr. Sica: I provide a precaution because the package label for all of them says that you shouldn't, but if there is a clinical indication, such as proteinuric renal disease, a systolic form of heart failure, or a high renin hypertension state that is only responsive to ARBs, then I cautiously proceed.

Dr. Black: Has there been any angioedema reported due to aliskiren or other renin inhibitors?

Dr. Sica: Random. We don't know. We don't have a mechanistic basis. It may be just background noise. If we subtract what we see in the population, the frequency with which it occurs in patients treated with aliskiren is not very different.

Dr. Black: I recall the LIFE (Losartan Intervention for Endpoint reduction in hypertension) study[1] in which the atenolol group had more angioedema reported and adjudicated than the losartan group. Do I have that right?

Dr. Sica: Yes, you have that right. There was another trial called the CHARM-Alternative trial,[2] in which people with ACE inhibitor complications -- predominantly cough, but with a reasonable cohort of patients with angioedema -- were rechallenged with candesartan. About 4% of patients who previously had angioedema redeveloped it. That is the number that resides in the literature. If you have a reason to use the ARB, feel free to use it with a precautionary note to the patient. However, if you don't need the ARB -- it is just randomly being added and you don't see any benefit -- then why rock the boat?

Dr. Black: I agree. Thank you very much.

Dr. Sica: You're welcome.


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