Cholesterol-lowering combination found to have limited benefit (again) and now is linked with increased risk of cancer

Back in January I wrote about the long-awaited results of the so-called ENHANCE trial in which two cholesterol reducing drugs (ezetimibe and simvastatin) were pitted against just one (simvastatin) in terms of their ability to slow the progression of the gumming up of the arteries known as atherosclerosis. Even though the dual-therapy was more effective in reducing so-called ‘bad cholesterol’ (LDL cholesterol), it did nothing to improve the condition of the arteries. If anything, the progression of atherosclerosis was worse in those taking two medications rather than one (though this was not statistically significant). The fact that these results were disappointing (to say the least) might be why it took a couple of years for the manufacturers of ezetimibe and simvastatin cough them up.

In the USA, the combination of ezetimibe and simvastatin is sold under the name of Vytorin. There, this product has been passed by the regulatory authorities on the basis of its ability to reduce cholesterol levels. The assumption here, of course, is that reduced cholesterol levels will translate into meaningful improvements in terms of things like heart attack rates (both fatal and non-fatal) and overall risk of death. However, while the ENHANCE study did assess this specifically, the fact that Vytorin brought no improvements in the extent of atherosclerosis as measured in the study suggests that ‘clinical’ endpoints such as heart attack risk might not have been improved either.

This week saw the announcement of another study of Vytorin. This 4-year study assessed the effect of Vytorin (or placebo) in individuals suffering from a narrowing of the aortic valve in the heart (this valve is found at the junction of the heart and the main artery in the body ” the aorta). The medical term for narrowing of this valve is aortic stenosis. The study is known as the SEAS (simvastatin and ezetimibe in aortic stenosis). You can read about the results of this study here.

There was some good news from this study in that the drug, compared to placebo, reduced the overall risk of ischemic events such as non-fatal MI heart attack, bypass surgery and risk of the most common form of stroke. However, Vytorin did not bring benefits (compared to placebo) in terms of events relating to problems with the aortic-valve, valve-replacement surgery, hospitalisation because of heart failure, and risk of death due to cardiovascular events (e.g. heart attacks and strokes). Overall, Vytorin was no better than placebo in reducing the main (primary) end points it was designed to assess, namely, aortic-valve and cardiovascular events.

Like the results of the ENHANCE trial, the results of this one I think would be described as disappointing. But actually the news gets worse when one considers that the group taking Vytorin were found to be at statistically significantly increased risk of dying from cancer compared to the group taking the placebo.

Against this, though, two ongoing trials (known as SHARP and IMPROVE-IT) have failed to find such an association, apparently. However, cancer takes some time to develop and be significant enough to be diagnosed and cause death. While the SEAS trial lasted 4 years, the participants of the SHARP and IMPROVE-IT trials have typically been followed for 1-2 years, which may well not be long enough to properly assess the effect of Vytorin on cancer risk.

9 Responses to Cholesterol-lowering combination found to have limited benefit (again) and now is linked with increased risk of cancer

  1. cynic 23 July 2008 at 1:18 pm #

    This is a horribly unscientific point. I know someone who (overweight, middle-aged male) who had a very minor heart attack 15years ago. A couple of years of weight reduction and improved diet followed as person was anxious to avoid the need for bypass surgery (which they did avoid)
    Cholesterol (at the time up near 9) was targetted by all as the most important measure. This person is still on cholesterol lowering medication (chol below 6) and all the effort with diet, exercise and weight quickly faded.
    Still overweight, diet still not great, still doesn’t exercise. In fact recently has been diagnosed with type2 diabetes but these magical drugs are keeping the all-important cholesterol number below 6, so “the heart-disease is under control”

    i.e. maybe statins can help, but like a teeny-tiny bit with one tiny mechanism and only really affect outcomes if one makes and maintains major lifestyle changes.
    But what is going on is vast number of people thinking these cholesterol lowering drugs are like some kind of magic drug taking care of things.
    Do you see this behaviour in your clinical practice at all Dr B?

  2. Dr John Briffa 23 July 2008 at 3:23 pm #

    cynic

    “Do you see this behaviour in your clinical practice at all Dr B?”

    Not really, because, generally speaking, my patients are motivated to make (sometimes considerable) lifestyle changes in an effort to improve their health/wellbeing/longevity. But I do take your point.

  3. Cybertiger 23 July 2008 at 6:21 pm #

    The statins make no difference to all cause mortality in women. If they are saving women from fatal heart attacks then they are killing them from something else. So, why women are bothering to take statins?

  4. Biker 24 July 2008 at 6:15 pm #

    I have been taking Simvastatin (as well as other drugs) for several years. I was told Simvastatin was a life saver but now I am told it’s a killer. WHO DO I BELEIVE?

  5. Neil 24 July 2008 at 9:50 pm #

    Biker,
    you need to read pro and anti statin literature on the web, apply it to your own health and medical history and make a decision for yourself.
    Personally, I have found the work of Dr Malcolm Kendrick and the website http://www.thincs.org to be very useful. But thats me, ultimately it’s your body and your choice (informed). Sorry if you find this unhelpful, but we only have one shot at a life (IMHO) so I feel you have to do some reading and make yor own choice. You can’t read everything available, but try to cover both sides.

    Best wishes,
    Neil

  6. James H 26 July 2008 at 11:29 am #

    There is food people can eat that have been proven to lower Cholesterol e.g.

    Oatmeal
    Walnuts + almonds
    Olive oil
    Fish + Omega 3 (ground flaxseed + rapeseed oil)
    Do I dare say soya too ? ;)

    And of course some exercise. So why take medication?

  7. Cybertiger 26 July 2008 at 3:54 pm #

    @James H

    But is it the lowering of cholesterol that does you good? I certainly don’t believe it.

    PS. Malcolm Kendrick has also written a book called ‘The Great Cholesterol Con’.

    PPS. I understand that the absurd ‘war on cholesterol’ indulged in by the cholesterol-industrial-complex now costs the British taxpayer £2 billion per year. I should be on Prozac for my weepiness over this fact – but I’ve tried it and it doesn’t work.

    PPPS. The statins drugs do lower cholesterol but their modest benefits to the CHD sufferer are likely to be independent of this.

  8. Hilda 26 July 2008 at 4:41 pm #

    As Dr Briffa says it is about changing your whole lifestyle. Foods mentioned by James (apart from soya) can help lower cholesterol but the whole diet needs to be looked at. Fish oil is good but will need to compete with any processed oils such as margerine (all), fried foods, sunflower oil, mayonnaise, salad cream in the diet. All these oils need to be removed.

    All processed foods such as boxed cereals, cakes, biscuits need removing as well. Processed rapeseed oil is not good.

    Friends tell me that they ‘tried diet’ to reduce cholesterol but it didn’t work. This is because they trued the WRONG DIET given by the health service. Cutting out fats but not sugar! Eating a Paleo diet although the way our animals are reared is very different from Paleo animals.

  9. Hilda 26 July 2008 at 4:44 pm #

    Dr Briffa,

    Could you write something about vegetable oil as this is , with sugar, one of the worst problems with the modern diet.

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