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Nov 17, 2009

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A fourth possibility is that niacin adds a small cardiovascular benefit *and* ezetimibe adds a small cardiovascular harm.

Question: you seem to be saying that ARBITER was a secondary prevention trial. Yet some of the patients did not have known vascular disease. The trial included patients with a calcium score over 200 for women or 400 for men or Framingham risk scores over 20%. (There were also patients with diabetes who did not have known vascular disease, although diabetes is usually classified as a coronary risk equivalent.) Admittedly the primary prevention patients were *very* high risk. Still, if someone is totally asymptomatic but either has multiple risk factors giving them a high FRS or known extensive atherosclerosis as indicated by a high calcium score, isn't that still primary prevention?

In my view, the issue of whether ezetimibe promotes cancer and/or cancer death is still unresolved, although I know you are a skeptic on that issue. This trial does not tell us anything about that.

David, I am inclined to agree with your analysis. The only non-statin lipid-lowering agent that has shown event reduction in the primary prevention setting is gemfibrozil.

Having said this, drugs which prevent events in secondary prevention, usually also prevent events in primary prevention, although the NNTs are inflated. Again another reason why I rely on my atherosclerosis imaging to determine if a "primary prevention" patient is truly "primary", or rather actually a secondary prevention patient whose disease has not yet been unmasked by an event (worryingly, >30% of first MI are fatal).

I guess we'll have to wait for AIM-HIGH, HPS2-THRIVE, and IMPROVE-IT before we really know the truth on this.

Great blog.

Marilyn Mann's point is of course correct about the possibility of some harm from ezetimibe plus some benefit from niacin.

The "secondary prevention" issue is really just one of terminology. Since the definitions in ATP-III, a lot of people writing about lipids have called things "secondary prevention" if the patients have cardiac risk equivalents -- that is, if they have a condition or combination of conditions that gives them as high an event rate as if they had known CHD. This isn't truly secondary prevention, but it has become an acceted shorthand.

From my point of view it works because the relative risk reductions with statins are essentially the same whether patients are being treated for primary or secondary prevention, and so combining very high risk primary prevention patients with secondary prevention patients doesn't really alter the meaning of the discussion.

Dan is referring to the Helsinki Heart Study, I assume, which did show a decrease in cardiac events, but had no mortality benefit and had a concerning trend toward more cancers. I remain nervous about rates of noncardiac deaths in trials of nonstatin lipid lowering agents.

David Rind

interesting... i just got to know about all these now, thanks to your post... I'll say this is really informative

Like in all drug trials for "treating" cholesterol, the patients in ARBITER 6 had obviously self-destructive atherogenic lifestyles, BMI 31, 40% with diabetes, WC 41 inches. Such trials are unethical and should never be approved by any institutional review board. All patients in any drug trial for a disease of lifestyle, like CAD, must be done only after all subjects have a BMI of less than 25 and/or a waste circumference of less than half their height and be eating a low-fat Mediterranean type diet, proven by Ornish to reverse CAD.
http://medicalmyths.wordpress.com/drugs/statins/

It seems extremely unlikely that niacin really reduces events by 80%, since this should have been obvious in prior trials of niacin.

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