Vytorin® Crash and Burn? Is cholesterol dead?

Even worse, heterozygous hypercholesterolemia, and thereby LDL cholesterol, may not be the driver of plaque growth in this population. It is probably the number of small LDL particles, a factor which is not revealed by LDL cholesterol. For this reason, heterozygous hypercholesterolemia by itself is insufficient to cause heart disease and plaque growth is attributable to something beyond just LDL cholesterol. Some other factor(s) needs to be present. I would propose that it is the number of small LDL particles that determine whether or not plaque growth is impacted: When many small particles are present, atherosclerotic plaque progresses; when large particles are present, atherosclerotic plaque is less likely to develop. This issue was not addressed by this study. Instead, they relied on this flawed measure, LDL cholesterol.

So, there are substantial uncertainties in the Enhance Study, contrary to the absolute certainty expressed by people like Dr. Steve Nissen (who, by the way, has no expertise in lipoprotein disorders). It is premature to reach any firm conclusions from this study. The only conclusions that I personally reach are to ask 1) Is this yet another reason to question the entire lipid hypothesis as it stands? and 2) What would the results have been had LDL particle number and LDL particle size been examined, not just LDL?

I would not automatically conclude that Zetia causes carotid plaque. In my view, this is absurd. And I am definitely not one to come to the rescue of a drug or drug manufacturer. I am simply after understanding and truth.

I am always uncomfortable when put in the position of defending a drug or drug company. However, it is silly that this study has generated such attention. I suspect the media is waiting for another Vioxx-like debacle, with memories of concealed or suppressed data that suggested heightened heart attack risk that was dismissed by the drug manufacturer. (That's not to say that the company hasn't been trying to delay or modify the endpoint of the study, which they apparently have, much to the objections of the FDA.)

However, at this point, there is no reason to believe that this question possesses any parallels to the Vioxx fiasco.

Is LDL cholesterol an entirely worthless measure? Is the lipid hypothesis now defunct? I don't think so, but I do believe that our thinking is way overdue for a major overhaul, a revision of the hypothesis. More on that to come.