A few months back I mentioned a study called ENHANCE from the makers of Vytorin and Zetia that showed these drugs had no effect. That study has again entered the spotlight thanks to the release of the results and a pair of commentaries in the New England Journal of Medicine. The published results are essentially as was previously reported: addition of ezetimibe to an existing simvastatin regimen was of no benefit to patients, either in terms of reducing a measure of atherosclerosis or in the frequency of adverse events. The article (citation below) is worth checking out if you are interested.
As I mentioned in the previous post, these results are not definitive. The group under study was a high-risk group, but the fact that most of the participants were taking statins already significantly complicates the interpretation of the results. Is the lack of improvement with the addition of ezetimibe simply a case of diminishing marginal returns?
The really curious thing here is that ezetimibe did what it was supposed to do. Patients who took it had lower LDL levels than patients who didn't. Yet this reduction in LDL did not improve the measured outcomes. Does this mean that the measurement (intima-media thickness) was not appropriate? Or do these results imply that there are deficits in our understanding of the interplay between LDL, statins, and arterial disease? Additional studies using other observables are underway, but will not be completed until 2011. Until those results come in, the American College of Cardiology recommends that ezetimibe be used only when other approaches (notably statins) have failed to control LDL. I want to reinforce that these results do not mean that ezetimibe is dangerous, or even that it does not help prevent cardiovascular disease. The present situation is one of uncertainty. If you are presently taking ezetimibe as Vytorin or Zetia, continue to do so until you have a chance to discuss your medications with your doctor.
You can read the study here:
Kastelein, J.J., Akdim, F., Stroes, E.S., Zwinderman, A.H., Bots, M.L., Stalenhoef, A.F., Visseren, F.L., Sijbrands, E.J., Trip, M.D., Stein, E.A., Gaudet, D., Duivenvoorden, R., Veltri, E.P., Marais, A.D., de Groot, E. (2008). Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia. New England Journal of Medicine, 358(14), 1431-1443. DOI: 10.1056/NEJMoa0800742 OPEN ACCESS
The commentaries have DOIs 10.1056/NEJMe0801608 and 10.1056/NEJMe0801842. Both are open access.
PalMD of the Denialism Blog has another commentary on this issue.
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