A health research company just released a list of the 100 top drugs in America according to sales. 29th on the list, with sales of over $1.8 billion, is the cholesterol lowering drug ezetimibe, brand name Zetia.
This drug was released over 10 years ago because it worked really well in combination with statin drugs such as Zocor (simvastatin) to lower LDL cholesterol levels. It was released as a single agent and combined with simvastatin as Vytorin. The only problem was that in 2008 a study of the ezetimibe/simvastatin combination compared to simvastatin alone showed the combination did not improve measurements of arterial wall thickness which correlates with things like heart attacks and strokes.
Although cholesterol levels were lower in the combination arm, simvastatin was just as effective in achieving the more meaningful outcome. Ezetimibe appeared to increase cancer risk in another study, evaluating patients with aortic stenosis. A study which compared adding niacin or ezetimibe to statin therapy in patients with coronary heart disease in 2009 showed that, even though ezetimibe was very effective in reducing LDL cholesterol levels, it also increased the thickness of the arterial walls when compared to niacin. Niacin wasn’t nearly as good at reducing cholesterol levels as ezetimibe, but there were more cardiovascular deaths in the ezetimibe group.
This drug, whose only claim to fame is that it reduces a number on a chemistry panel, continues to be popular in both the US and Canada. An editorial in the Journal of the American Medical Association in 2014 wondered at the failure of very convincing evidence to make us stop prescribing it. The author concluded that it must be that the manufacturer (Merck) has been very effective at marketing ezetimibe and that patients’ and doctors’ fixation on reducing the cholesterol numbers has made it attractive in defiance of its lack of efficacy. Statin drugs, which also are not immune to controversy, may reduce the risk of heart attacks by reducing inflammation, not by reducing cholesterol levels per se. Since ezetimibe acts to reduce absorption of cholesterol from the gut, it may have no effect at all on inflammation or vascular health despite lowering cholesterol levels.
There are further studies still in the pipeline which may clarify the situation a bit more. It seems right now, though, that there is enough evidence that this is a bad drug for the Food and Drug Administration to rescind its approval. It would be nice to believe that physicians would take the initiative to change their prescribing habits, removing $1.8 billion dollars from our health care bill while reducing our patients’ pill burden, but apparently we are not stepping up to the plate.
Janice Boughton is a physician who blogs at Why is American health care so expensive?