I’ll start by mentioning a few of the more thoughtful blog reactions that alerted me to this issue, and with which I partially agree. DB has a series of entries , , ,  and Retired Doc weighs in with two posts , .
Despite claims that drug company marketing hijacks evidence based medicine the larger problem, in my view, is the hijacking of EBM by popular media (as happened after the Avandia meta-analysis). If the pharmaceutical industry sat on the ENHANCE results for almost two years as has been reported, it’s cause for concern. In today’s climate you can hardly blame the drug companies, though, for going slow and painstakingly examining the nuances of a controversial study before releasing the information. Once a study like this is out the media salvo (which tends to be adverse to the drug companies) takes over the discussion, stifling reasoned debate, spreading distortion, ignorance and more heat than light. I would submit that in some cases distorted media coverage is worse than no information at all.
So let’s put aside the New York Times for a moment and go to a reliable source. The American Cardiology had this to say in its commentary on the trial: According to the American College of Cardiology (ACC), this study deserves serious thought and follow-up. Yes indeed. But we’ve seen very little of that in the media reaction. The ACC’s summary of the trial contains essential facts for a proper understanding of the issue, largely ignored by the media. It deserves a careful read. I’ll offer a few observations here.
The study patients had familial hypercholesterolemia (FH) with a mean pre-treatment LDLC of 319mg/dl. LDLC was reduced by 41% in the Zocor group (to 188) and by 58% in the Vytorin group (to 134). That’s significant in view of the apparent “shock” that both treatment groups in ENHANCE showed atherosclerosis progression. But it’s not shocking at all. Although there are some conflicting data, previous studies have generally shown that it takes much lower LDLC levels than 134mg/dl to halt atherosclerosis progression. Although an on-treatment LDLC level above which atherosclerosis progression occurs is not precisely known multiple studies (such as this one) suggest it’s around 100mg/dl. Therefore while post treatment LDLC of 134mg/dl in a patient with FH is quite impressive it would not be expected to halt progression.
Although non-progression of atherosclerosis (or, better yet, regression) should predict favorable clinical outcomes and is thus desirable there is no direct evidence that such results are required in order to produce clinical benefit. Multiple lipid trials, in fact, overwhelmingly suggest otherwise. Many trials which achieved more modest LDLC targets than those associated with non-progression (4S, CARE, WOSCOPS, AFCAPS/TEXCAPS to name a few) have been associated with reduction in clinical events.
A New York Times piece egregiously distorted the results of ENHANCE, quoting one cardiologist as saying the results were “shocking” and implying that Vytorin caused atherosclerotic plaque progression to almost double:
The Enhance trial was meant to prove that Vytorin’s combination of Zetia and Zocor would reduce the growth of fatty plaque in the arteries more than Zocor alone. Instead, the plaque actually grew almost twice as fast in patients taking the combination.
There are many distortions and faulty assumptions in the article. First of all, ENHANCE measured carotid intima-media thickness (IMT), a controversial surrogate for atherosclerosis, not atherosclerotic plaques. Secondly, there was no significant difference in the rate of progression between the two treatment groups. At p=0.29, the results of IMT progression difference didn’t even approach statistical significance.
Do the ENHANCE results negate the value of LDLC reduction? Not by a long shot. The evidence that LDLC reduction matters is convincing and includes diet trials, non-statin drug trials and epidemiologic data.
If an ongoing trial fails to show that Vytorin reduces clinical events, that will be shocking. Given what we know now, if I had FH I would do everything I could to reduce my LDLC. If my treatment options were confined to Zocor and Vytorin I would choose Vytorin hands down.