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 .
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.
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.