How do doctors come to recommend and prescribe cholesterol medications for which there are no proven benefits?

Traditionally, cholesterol management has been based on the concept that blood cholesterol levels should be below a certain level. Sometimes, taking a statin drug may be adjudged to have not reduced cholesterol sufficiently. Some people do not tolerate statin drugs. In these sorts of circumstances, someone may be offered another drug to reduce their cholesterol to an ‘acceptable level’, and that drug is quite likely to be ezetimibe.

Ezetimibe blocks cholesterol absorption from the gut, and therefore can reduce levels of cholesterol in the bloodstream. The usual recommended dosage of ezetimibe is 10 mg a day. However, a new study just published in the Canadian Journal of Cardiology (CJC) shows that 20 mg of ezetimibe taken daily produces statistically significant reductions in total cholesterol and LDL-cholesterol compared to the 10 mg dose [1].

Here’s the summary of this study:

20 mg daily reduced total and LDL cholesterol further in patients receiving statin therapy compared with 10 mg daily. Prospective studies are required to show whether the higher plasma levels of ezetimibe and its active metabolite in patients taking the 20-mg dose have any detrimental effects. Increasing the ezetimibe dose to 20 mg daily might be an interesting potential approach for patients who fail to reach lipid targets on ezetimibe 10 mg daily along with maximally tolerated doses of statin.

The focus here is on people reaching their cholesterol ‘target’. Implicit here, is the promise that getting cholesterol down to a particular level will confer protection from cardiovascular events such as heart attack and stroke. However, whether this works in practice has never been tested.

The thing doctors and researchers should be focused on is not the impact ezetimibe (or anything else) has on cholesterol levels, but its effects on health. Does ezetimibe, say, reduce the risk of heart attack, or dying from heart attack, or overall risk of death, say?

The sad reality is that not one single study demonstrates any ‘clinical’ benefits such as these.

I noticed on twitter that the CJC study has been highlighted by Dr Thomas Dayspring, as US-based ‘expert’ on blood fats (his twitter name is ‘DrLipid’). Via twitter, I asked him if he was aware of evidence for the clinical benefits of ezetimibe.

He pointed me to trials of ‘surrogate’ markers (e.g. blood cholesterol levels). There could be 100 of ‘positive’ studies, but they don’t tell us what we need to know. For ‘clinical’ evidence he offered up two trials, the so-called ‘SEAS’ and SHARP’ trials, which I have written about elsewhere on this site.

In both of these studies a combination of ezetimibe and a statin was found to improve certain clinical outcomes. Dr Dayspring can put this up of evidence for the benefits of ezetimibe, but it would not stand up in court. Why, because the benefits were seen with a combination ezetimibe and a statin. How do we know if the benefits were due to the statin, or ezetimibe, or both? We don’t.

It seems to me that either Dr Dayspring either has a fundamental inability to understand the relevance of research findings, or is somehow hopelessly biased towards ezetimibe (or both).

Ezetimibe is licenced and prescribed purely on the basis of its cholesterol-reducing properties. The idea that cholesterol reduction is necessarily healthy has been thoroughly disproved by a wealth of evidence that shows, for instance, that cholesterol reduction through diet and through the use of some other drugs simply fails to deliver on its promise in terms of saving lives (the clearest and most important endpoint of all).

I do not blame the public for not realising the importance of this distinction, so effective has been the ‘mind control’ in this area. However, I have to say I think that doctors should really know better. Front and centre in a doctor’s thinking process when managing patients should be whether the proposed is likely to improve the condition of their patient. We actually have zero evidence that this is the case for ezetimibe, and I therefore believe there is zero justification for prescribing it.

References:

1. Ziada A, et al. Incremental Lowering of Low-Density Lipoprotein Cholesterol With Ezetimibe 20 mg vs 10 mg Daily in Patients Receiving Concomitant Statin Therapy. Can J Cardiol. 2013;29(11):1395-9.

5 Responses to How do doctors come to recommend and prescribe cholesterol medications for which there are no proven benefits?

  1. Trish Cherry. 15 November 2013 at 1:19 pm #

    Three years ago now, I had a “very strong disagreement” with the Lipid specialist at my local Hospital. I had what was thought to be FH and all my children and grandchildren had tests. Long story short, when I discovered the effects of ezietamibe, which I had looked up because of certain side effects, I wrote to the Lipid specialist complaining that I felt it was wrong to put anyone on a drug that had not been proven safe. Since I had also come across Malcom Kendrick at the time, I told her that I had decided to not worry about my high Cholesterol levels and was stopping all drugs and would not be attending the clinic again.

    Her reaction was best described as comical. She said that she was attending a conference the next week with the British Heart foundation and that she would be reporting my case and briniging up the subject of “these amateurs who were writing books and endangering the lives of the people who read them” She also wrote to my surgery and put in a disclaimer and suggested that they do the same. My GP wrote back to her and said that while she agreed with the Lipid Specialist she has to honour the wishes of her patient “who was very well informed of the subject of Cholesterol!”

    The funny part of it is that while I have been following the Paleo way of eating with Zoe Harcombe, even though I have had numerous routine tests for various reasons, no one ever mentions my Cholesterol levels. So I can only imagine that they must be fairly low. I have yet to bring up the subject sometime, but at the moment I am letting sleeping dogs lie.

    Also I discovered recently that people with kidney problems (poor function) can have high Cholesterol, as it is the body fighting back with the necessary extra Cholesterol , as I have only 30% function in one of my kidneys I imagine that is the reason why my C levels have been high and it is not FH.

    Apart from the kidney problem I am in excellent Health and watch other people my age (69) in such poor health. I put this down to the fact that I watch what I eat and have always had to watch my weight. I did not always get it right and used to binge a starve in my younger days. But that is another story.

    I now run a coaching service for people with weight and food issues as I know enough about these problems to help others and this is my passion in life.

  2. Lynne Smith 15 November 2013 at 1:21 pm #

    I saw the Twitter exchange with @drlipid- his posts send out confusing messages, but @drbriffa has four times more followers so maybe he will listen and come round (?like dr Oz) when challenged.

  3. Z.M. 15 November 2013 at 1:41 pm #

    Dr.Briffa,

    having read the SHARP and SEAS trials I think it’s misleading to suggest as Dr.Dayspring did, that these trials showed benefits.

    In the SEAS trial there was no difference between the simvastatin plus ezetimibe group and placebo group with regard to the primary outcome including no difference with regard to the hard outcomes such as cardiovascular death or overall mortality despite massive cholesterol lowering. This is a failure. Any other conclusion is simply data dredging.

    In the SHARP trial most of the “benefit” was driven by soft endpoints such as “revascularisations”. There was no significant difference in the major coronary events (non-fatal + CHD death) which included no difference whatsoever (not even a trend) in CHD death and no difference whatsoever in overall mortality.

    Also there was controversy with regard to the unclear plan (http://www.trialresultscenter.org/study8081-SHARP.htm):

    “There is a certain incertitude concerning the primary endpoint (apparently changed by the Steering committee before the trial ended but this change was not endorsed by the sponsor) Statistical analysis plan is not clear too, with or without the inclusion of patients initially allocated to simvastatin alone and re-randomized to either combination or placebo for the remainder of the study period”.

  4. NM 16 November 2013 at 12:25 pm #

    Lynne Smith: If you research Dr Dayspring’s sources of funding, you will find he has very little inducement to change his mind.

  5. Isabel Dickens 19 November 2013 at 3:31 pm #

    I had a cholesterol blood test several months ago which gave a reading of 6.7mmol/L ie what my GP called “an unacceptably high cholesterol reading.” She said I would some tablets to bring it down.

    When I asked for a breakdown of the result she told me “your bad cholesterol result is good – at the low end of the normal range at 0.4mmol/L” . She confirmed this was the triglyceride level.

    So I asked her what the “good cholesterol” result was and her response was “it’s not as simple as that”

    I declined the medication.

Leave a Reply to Z.M. Click here to cancel reply.