Ezetimibe is an effective cholesterol-reducing drug (it works by blocking cholesterol absorption from the gut). I came across a study this week from a group of researchers based in Michigan in the US which concluded that ezetimibe appeared to have a ‘protective effect on major AD [atherosclerotic disease] events and all-cause mortality…’ [1]. In other words, the authors were suggesting that ezetimibe can reduce the risk of heart attacks, strokes and overall risk of death. I have to admit, I was somewhat surprised by this conclusion, because I was not aware of any good evidence that supports it.
Actually, in trials, ezetimibe has not performed well at all. Not one single study has shown it to have benefits for health. In fact, in one study, there was evidence that it might actually worsen the development of atherosclerosis (the narrowing process in the lining of the arteries). And other evidence shows that the drug can increase the risk of death from cancer.
So, how were the paper’s authors able to put such a positive spin on these results? The answer was to essentially ignore these results, and ‘analyse’ the data is a completely different way. The paper in question is based on what is known as ‘epidemiological’ evidence. This sort of study looks at associations between things. In this study, the health outcomes in people taking ezetimibe and those not taking ezetimibe were compared. Those taking ezetimibe were found to have better outcomes, hence the study’s conclusions.
However, while epidemiological evidence may find associations between things, that does not mean that one thing is causing the other. So, while ezetimibe use and better health outcomes are linked, that does not mean the drug is causing those better outcomes.
It is possible, for instance, that individuals taking ezetimibe may be generally healthier than those not taking it, because they may be more health-conscious and more likely to seek medications they believe will benefit them. Also, sicker individuals may be less likely to be prescribed medication because of fear of side-effects or drug interactions. What this means is that the health benefits linked with ezetimibe may have nothing to do with ezetimibe itself, and everything to do with the general characteristics of people who take this drug.
To really know for sure whether ezetimibe is beneficial to health, we require clinical studies in which ezetimibe is tested against a dummy drug (placebo). But, as we already know (see above) we have no positive studies of this nature. And where ezetimibe has been added in with a statin drug, no added benefits have been found, and in fact some evidence shows worse outcomes.
In short, we have no evidence at all the ezetimibe benefits health, and at least some that suggests it is harmful to health. These are the facts we have based on the best available clinical evidence.
The authors of this recent paper do seem to have effectively junked the best and most reliable evidence we have, in favour of notoriously unreliable epidemiological research. This is another example of what appears to be a desperate attempt by some researchers to attach a benefit to a drug which evidence shows does just not exist in reality.
References:
1. Hayek S, et al. Effect of Ezetimibe on Major Atherosclerotic Disease Events and All-Cause
Mortality. Am J Cardiol. 2012 Dec 4 [Epub ahead of print]
The rationale behind the intended action of ezetimibe seems a little suspect.
Even the most decadent of western diets only supplies about a quarter of the cholesterol the body needs at most. So cholesterol synthesis within the body (generally in the liver) makes up the the deficit. Cholesterol is a valuable constituent of bile, and cholesterol is so valuable and purposeful in the body that a high proportion of the cholesterol in bile is reabsorbed from the gut, recirculated, and recycled.
By the nature of these affairs you’d expect a feedback system. Eat less cholesterol and the liver ramps up synthesis. Eat more cholesterol rich food and (simplistically) you’d expect the call for synthesis to be reduced. But cholesterol is central to the transportation of fats and fat soluble vitamins in various lipoprotein ‘vehicles’ going about legitimate business. We ought not rule out that cholesterol availability is dynamic according to the logistical requirements of ferrying legitimate traffic of fats, phospholipids and fat soluble vitamins around the body.
You wouldn’t really expect something that blocks cholesterol absorption from the gut make a difference to cholesterol counts, but if it did I’d be curious to know if ezetimibe can distinguish between ingested cholesterol and the general cycling of cholesterol involved in the cycling of bile. If ezetimibe alters the results returned from lipoprotein tests (cholesterol) then it is interfering in something, but not necessarily in the interests of greater good.
Another example of ‘cooking the books’ it would seem! Uve Ravnskov also recently came to the conclusion that ‘positive’ epidemiological results for cholesterol-reducing drugs missed (deliberately?) some key characteristics of those prescribed such medication e.g that those with high cholesterol often had ‘better’ health overall due to the protective effect of cholesterol on the body. Keep up the good work Dr Briffa – we need to be aware of real scientific questioning!
I am a 65-year old woman who actually has atherosclerosis and therefore a vested interest in treatment. Statins triggered severe memory loss and muscle pain as well as stabbing pains in the head. Any drug with such side effects should be taken off the market. Doctors need to revisit the cholesterol myth.
@suzy Would be interested to know if you have stopped statins and if so, if you take other natural or prescribed medication instead? Am curious because have been told I have high cholesterol and statins suggested but not taken them due to the issues I have discovered reading on comment sections of health blogs such as this.