In 2002 the Food and Drugs Administration (FDA) in the US licensed the cholesterol-lowering drug ezetimibe (Zetia). This medication reduces ‘unhealthy’ LDL-cholesterol levels by about 20 per cent. The assumption here is that this will reduce the risk of heart attacks and strokes. When ezetimibe was licensed, all of a sudden doctors had a new toy to play with and many rushed to prescribe it.
Then in 2008 came the release of results from the so-called ENHANCE study. This tested the effect of adding a ezetimibe to a statin on build-up of plaque on the inside of the body’s arteries, compared with taking a stain alone. The results of this study needed to be prised from its drug company sponsor, and no wonder: the results showed no benefit from the addition of ezetimibe and the additional cholesterol reduction it brought.
This, one might argue, would have sounded some sort of death knell for the drug in the ears of doctors. But a new study published in the American Heart Journal  suggests that this ‘bad news’ for ezetimibe was not precisely reflected in the prescribing practises of doctors.
For example, in Canada, it appears that prescriptions for ezetimibe increased steadily over from 2002 to 2009, with no let-up post-publication of the damning ENHANCE study. In the US, the situation was different, with prescription rates falling by about half after ENHANCE was published. However, rates of prescriptions in the US remained higher, overall, than in Canada.
We doctors like to believe ourselves to practice ‘evidence-based medicine’. But, in reality, we sometimes seem to have the capacity to ignore the evidence. There are plenty of reasons why this might be so, certainly one of which includes the fact that, historically, doctors have been encouraged to treat cholesterol levels down to a certain level. This means, in effect, that doctors have been encouraged to focus on cholesterol and their attention has been somewhat diverted from what is truly important (health outcomes). The fact is this: not one single study ever published has provided evidence that ezetimibe benefits health outcomes.
Late last year, the American College of Cardiology and the American Heart Association issued new guidelines on the management of cardiovascular disease. Here is one of the edicts from this set of guidelines:
Nonstatin therapies do not provide acceptable ASCVD [cardiovascular disease due to the clogging-up process known as ‘athersclerosis’] risk reduction benefits compared to their potential for adverse effects in the routine prevention of ASCVD.
If doctors act on this advice, then ezetimibe prescriptions should drop to precisely zero.
Should a doctor prescribe ezetimibe, then I don’t think it’s unreasonable for their patient to enquire about the evidence for this recommendation. This request may not get the best reaction, but I’d suggest that only through this sort of question may some doctors get to review their knowledge and practice, and offer truly evidence-based care.
1. Lu L, et al. Impact of the ENHANCE Trial on the use of ezetimibe in the United States and Canada. Am H J published on-line 27 February 2014