Robert W. Morrow, MD: Thanks, Henry. I'm Bob Morrow, Associate Professor of Family and Social Medicine at the Albert Einstein College of Medicine. I have been in general family practice for 30 some-odd years -- mostly odd years. That's why we call it the borderline medical practice. I am also the Associate Director of Interventional Continuing Medical Education at the Center for Continuing Medical Education at Albert Einstein College of Medicine.

The question I'm posing to you is one that has been puzzling to me. Having been brought up in the generation before calcium channel blockers (CCBs) got their big push as the expensive new guys on the block that weren't any better, I'm used to sticking with beta-blockers, thiazides, and angiotensin-converting enzyme (ACE) inhibitors before going to CCBs as the second- or third-line drug, particularly in diabetic patients. Now we have a resurgence of the use of amlodipine. This is a drug that, in a good number of my patients, makes ankles swell. One of the reasons we treat blood pressure is to prevent heart failure and to prevent renal failure. Where does amlodipine fit in with all of that?

Dr. Black: Excellent question, and one that involves a little history. The first CCB or calcium antagonist was released in 1967, and it was verapamil. Over the years, CCBs have been lumped together because they block the entry of calcium into cells. In fact, every antihypertensive drug does that, directly or indirectly. We ought to view calcium antagonists as existing in 2 different flavors: non-dihydropyridines such as verapamil and diltiazem, and dihydropyridines, which are just about everything else. Verapamil and diltiazem slow heart rate, maybe improve insulin sensitivity, are not diabetogenic, and are pretty much metabolically neutral.

Dihydropyridines came along later, and they are very powerful antihypertensive drugs. In fact, amlodipine was originally in a study [in which it was administered at] 2.5 mg to 20 mg. At 20 mg, edema is invariable, so only 2.5 mg, 5 mg, and 10 mg are now currently available, but someone could take 2 if they wished. This is especially an issue for women, but not so much for men. I rarely go beyond 5 mg, but for women, I will often go to 10 mg.

Amlodipine has been the comparator drug in a large number of studies, including the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Amlodipine does very well when it comes to preventing problems, but it seems to cause heart failure, reasonably commonly. If a patient has heart failure, clearly you are not going to be using amlodipine. In the ALLHAT study, when it came to any number of issues, especially for stroke prevention, amlodipine was almost as good as chlorthalidone was.

The British recently stated in their National Institute for Clinical Excellence (NICE) guidelines that, for individuals over 55 years of age or of any age if of African or Caribbean descent, either a thiazide-like diuretic or a CCB is the first drug of choice, and the second drug is an ACE inhibitor or an angiotensin receptor blocker, with a diuretic after that. The NICE group's recommendation is probably the most evidence-based that we can see. They have the ability to look at enormous numbers of records through the National Health Service in Britain, and they have the ability to look at billions of bits of data, and that was their recommendation.

Amlodipine is an excellent drug for preventing strokes. In ALLHAT, glomerular filtration rates went up a little bit and stayed there, but people with renal disease didn't do worse. In the African American Study of Kidney Disease and Hypertension (AASK) study, which compared amlodipine with metoprolol and ramipril, patients did fine on amlodipine if they did not have proteinuria. If they did have proteinuria with amlodipine, they stopped the treatment. Therefore, when somebody asks what I would give to a patient, what my first-choice drug would be, my question is always, "Tell me about the patient."

Dr. Morrow: Exactly.

Dr. Black: If the patient is an older African American who does not have heart failure or who might have angina or something else that a CCB would help, that's one thing. If the patient is a young, white individual who is asymptomatic, I'm not going to pick something like [amlodipine]. I think that's how we should approach each case.

Dr. Morrow: The New York State Medicaid Program's take on this, particularly the analytics from the State University of New York, is that we can't really distinguish between races. In some studies, race may have been poorly controlled. Also, you can't look at a person's degree of melanin and say that he is of this race, that race, or some other race. It becomes complex, and they don't suggest that you use it for your decision-making. I tend to agree with that. I will say that I frequently get into more trouble practically than I expect with the drug in terms of edema and development of what appears to be a decreased ejection fraction. I'm not convinced that it has a renal-protective mechanism that you would see over many years with an ACE inhibitor. Even knowing this new stuff, I tend to use amlodipine as number 3, and it would be good if we had more guidance from a national guideline. Do you know what is holding that up, or should we talk about that next time?

Dr. Black: We can talk about that next time. Thanks very much.

# posted by roodbont @ 5:14 AM