(Some) doctors suggest that lower cholesterol levels may not be better after all

About a month ago, I reported on a study (known as the ENHANCE trial) which found that two cholesterol agents (simvastatin and ezetimibe) were no better than one (simvastatin) in terms of reducing the narrowing of arteries in the body. This blog post was based on data that had to be, it seems, forced out of the manufacturers of these drugs by a congressional hearing in the US. The results finally came to light a full two years after the study had been completed. And on Sunday the study results were formally published on-lined in the New England Journal of Medicine [1]. Bearing in mind the fact that some ‘negative’ studies are not even published, I suppose we should be thankful for small mercies and at say ‘better late than never’.

The results of the study were also discussed last weekend at a meeting of the American College of Cardiology meeting in Chicago, US. The conclusion of an expert panel was, in essence, that there is no evidence that simvastatin and ezetimibe is better than taking a statin alone, so doctors should ‘turn back to statins’ [alone] in their management of raised cholesterol.

Rather predictably, I suppose, the manufacturers of ezetimibe ” Schering-Plough – went on the offensive. Dr. Robert Spiegel, chief medical officer at Schering-Plough told Reuters news agency: “We were very disappointed in the ACC panel. We had expected a balanced discussion and we really didn’t think the panel today served patients well”. I’m wondering how patients could have been better served than to be told that the addition of one drug to another doesn’t seem to work. And also, how did it ‘serve’ individuals to take ezetimibe for two years while its manufacturer sat on the results of a negative study?

Schering Plough issued a joint statement with Merck (manufacturers of simvastatin) in which it is claimed that the most likely explanation for why individuals on double-barrelled therapy did not do any better than those on simvastatin alone was because the patients in the study had already been aggressively treated with statins, and there are limits to how much more they could improve.

Of course, this ‘explanation’ (if that’s what it is) seems to neatly dodge the fact that the two drugs led to a significantly lower cholesterol level than simvastatin alone. So, if cholesterol causes a gumming up of the arteries, how come lower cholesterol did nothing to help in this respect.

In my first post about this I put forward theory that one explanation for this finding is that cholesterol doesn’t actually ’cause’ cardiovascular disease. This may seem a rather radical stance, but it is supported by the results of this study. And consistent with this notion is that fact that statins may lower cholesterol, but also have a number of mechanisms of action that may explain the fact that they reduce the risk of cardiovascular disease.

Now, I’m not expecting a big rush of doctors and scientists denouncing the cholesterol hypothesis and suggesting that cholesterol does not cause cardiovascular disease. Such a move would, I dare say, cause the sky to fall in. However, the ENHANCE study has at least led to some interesting murmurings. The ENHANCE trial is accompanied by an editorial in which the cholesterol mantra ‘lower is better’ is at least questioned, and that can only be a good thing, I think.

However, the authors of this editorial would not be the first to suggest that current vogue to drive cholesterol levels ever lower may be flawed: a review published in the Annals of Internal Medicine in 2006 concluded that achieving the current cholesterol targets has not proven to be either ‘beneficial or safe’.


1. Kastelein JJP, et al. Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia NEJM [epub 30th March 2008]

2. Brown G, et al. Does ENHANCE Diminish Confidence in Lowering LDL or in Ezetimibe? NEJM [epub 30th March 2008]

3. Hayward RA, et al. Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem. Ann Int Med 2006;145:520-530

12 Responses to (Some) doctors suggest that lower cholesterol levels may not be better after all

  1. bob 2 April 2008 at 8:36 am #

    as a lay person why is everyone taking this in isolation surely if you stack up the odds and include cholesterol, with being overwt , high blood pressure, smoking etc then surely it is relevant!

  2. Dr John Briffa 2 April 2008 at 12:25 pm #

    Generally speaking, risk factors need to be assessed in isolation if we’re going to be able to discern whether something is a true risk factor, or a risk ‘marker’ (something that is associated with a disease but doesn’t ’cause’ it).
    You can assert that cholesterol is ‘surely’ relevant, but perhaps you could expand on why you take that view. Maybe you might even quote some science too.
    Your lay status doesn’t necessarily give you the luxury of making statements and assertions without offering anything to support them whatsoever.

  3. Susan 3 April 2008 at 8:31 pm #

    Re. the information about statins and the doubtfulness of their benefits Dr Briffa has raised periodically. Todays Radio 4 Investigation prog. about the use of statins in Primary Health Care prevention confirms what you have been saying, and what is of particular concern is that GP’s are financially incentivised / penalised if they “fail” ot “suceed” with individuals in their care and the government cholesterol target. Its medicine by crude target and financial pressure. This applies in many ways, as there is now a discriminatory blanket restriction to 28 days for those of us entitled to free NHS repeat prescriptions. No doubt statins will be made exempt, as is HRT, but not medication for hypthyroidism.

  4. Susan 3 April 2008 at 8:33 pm #

    the url for this prog is http://news.bbc.co.uk/1/hi/help/3681938.stm

  5. Vitallywell 5 April 2008 at 9:03 pm #

    The combo drug not only not effective but has it’s own potential side effects which are not completely studied or known.

    My wife just received a letter from our health plan that a particular combination of her meds are KNOWN to cause seizures (from a Harvard computerized database). One doctor prescribed them, another doctor just did a review of her meds and neither was aware of the seizure danger when combining Tramadol and another prescribed med!

    My wife used to think I was a conspiracy nut when it came to my view of most pharmaceuticals (not all). She is becoming wary of the pharmaceutical pushing doctors as I am. Do your own research people(in addition to professional advice), it may save your life.

  6. Sue 6 April 2008 at 12:34 am #

    Isn’t it true that most patients that had heart disease or died of heart disease had low cholesterol levels?

  7. helen 7 April 2008 at 1:47 am #

    Its not the cholesterol that gums up the arteries from all I have read on the subject & there is lots of information out there, simplistically – cholesterol is the substance sent out by the body to repair the damage done to the artery walls by inflamation & cell destruction caused in part to sugar & a lack of various vitamins & minerals in our diets. So how does it cause anything if it is an normal part of our bodies maybe we should be looking at the real causes like smoking, sugar(carbohydrate consumption) etc It is pretty obvious once you begin to investigate the claims of cholesterol causing heart disease to see that this is not the case at all high cholesterol is being caused by a whole lot of things that actually contribute to heart disease it, in itself is not the cause of the heart disease. It would seem that poor nutrition is one of the major causes. It would appear that the cutting out of saturated fat & the consumption of high levels of carbohydrate in the diet is more of the cause of heart disease than cholesterol could ever conceivably be.

  8. Hilda 8 April 2008 at 7:25 pm #

    Years ago Adele Davis wrote that just because cholesterol iis found in the blocked arteries this does not mean that it CAUSES the blocking. There may not be an association between the AMOUNT in the BLOOD and the amount in the arteries. If cholesterol rushes to a site in the artery that has been damaged by free radicals then it is not cholesterol per se but the free rad damage that is the problem.

    An analogy : Fluid retention means that we are storing too much water but water is the not the CAUSE of fluid retention.

  9. Mo 11 April 2008 at 11:30 pm #

    The interesting thing is that according to WHO MONICA figures there is no correlation between high cholesterol and cardiac incidences. There are countries with populations who on average have higher cholesterol values and much less heart disease than the UK. It is of note that those with low cholesterol are just as susceptible, if not more, to heart problems.

    Our skins contain a precursor chemical that becomes vitamin D in sunlight, in absence of sunlight the precursor accumulates as – I assume – LDL cholesterol. Since vitamin D is an anti-inflammatory, and indeed a Spanish trial (can’t find link off hand) found that the biggest selling drug in the world Lipitor/atorvastatin raises levels of D to some degree, as well as having other effects that might be of little extra use.
    D3 (natural D/cholecalciferol) also does something to the particle size of LDL cholesterol, which is much more important than the quantity. It also reduces trigylcerides.

    This is also challenges the mainstream notion. While we have an understanding of HDL, LDL and trigylcerides to a best degree, we see ads for products with tag lines like “lower your cholesterol” which is laughably basic. Low total cholesterol will kill you for sure.

    Furthermore, eating a McD’s doesn’t add to a landfill of sludge in your arteries; on examination it makes you laugh. What is the concern is arterial calcification. That is calcium in the arteries.

    Humans are the only animals to consume another animal’s milk and then after childhood continue to consume dairy in order to keep our bones healthy. Yet vitamin D is the director, without which D is sloppily pasted to the bones. Most of us don’t get enough D as again we’re the only animals to wear clothes and live indoors – and year round. D not only directs calcium where to go, it also tells it where not to go.

    I’m heartened by developments. It’ll take time but the cholesterol myth will go. We’ve had statins in our midst for 20yrs and they didn’t give us the expected revolution. Bring back nature!

  10. Susan 11 July 2008 at 7:49 pm #

    If you haven’t seen this already, you might be interested in the latest insanity from the US. Recommendations for children that include cutting fat in the diets of children under 2 and prescribing statins to 8-year-olds. (http://www.proteinpower.com/drmike/statins/nominees-for-the-reckless-award/)

    To my mind some of the greatest contributors to children’s obesity are sugared drinks and cereals. I’m over 50, and in my day soft drinks were a special treat and sweeted cereal was considered too expensive.

  11. Fed-up 4 August 2008 at 4:25 pm #

    This may seem random and unrelated but….I think the problem here is that as with all medical problems in life, people are quick to try to blame cholesterol or other medical problems for their health issue. When you should in fact be blaming yourself. Educate yourself on what your genetic weaknesses are and then adjust your daily life including diet and activity levels to achieve the results you need. Too many fat people have medical issues and try to treat them with drugs, when if they would just get up off their fat bottoms and exercise and cook a healthy meal, many of their issues would melt away with the fat. SO….what I am saying is not that while this article states that lower cholesterol levels are also bad for you and therefore you are buggared, what you should do is you should educate yourself and eat food as medicine for your body. Children particulalry should not be given medicine for cholesterol and ADD and all that stuff, they should be encouraged to play outside and eat right and TURN OFF THE TV AND PUT DOWN THE PLAYSTATION CONTROLLER. Stop listening to the media and listen to your body….Sheesh!


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