Today the official results of the ENHANCE trial were finally presented, simultaneously, at the American College of Cardiology Scientific Sessions in Chicago, and in print in the New England Journal of Medicine. While some were half expecting the sponsors to pull a rabbit out of the hat at the last minute, and show that Vytorin actually does provide some measurable benefit to patients with high cholesterol levels, that did not happen.

There were no surprises of note.

As I have previously described, despite the significant reduction in LDL cholesterol in study patients who took Vytorin (a combination of ezetimibe and simvastatin) as compared to patients who took generic simvastatin alone, there was no benefit in the endpoint measured. (That endpoint, a measure of wall thickness in the carotid artery, generally reflects the amount of coronary artery disease that is present.) There appears to be no benefit to taking Vytorin (or its cousin, Zetia, which consists of just ezetimibe) instead of a statin alone.

Indeed, the fact that carotid artery wall thickness actually increased more in patients taking Vytorin than those taking simvastatin alone (though the difference was not statistically significant) raises at least the possibility that Vytorin and Zetia ought to be avoided unless they are really necessary to achieve target cholesterol levels.

In general, for patients whose cardiac risk dictates that they need to use drugs for cholesterol reduction, the order of drug therapy generally ought to be: 1) statins alone, up to maximum recommended doses as necessary; 2) if needed, add those drugs that have been shown to improve clinical outcomes when added to statins (nicotinic acid, bile sequestrants, and fibrates); 3) only when all else fails, consider Vytorin or Zetia.

Patients currently taking Vytorin or Zetia should not stop the drugs before talking with their doctors, but they ought to discuss with their doctors whether the drugs were begun appropriately, in light of what now has been officially reported.

Read here a summary of what we know about statins and cholesterol.

_Sources:

Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008; 358:1431-1443.

Brown GB, Taylor AJ. Does ENHANCE diminish confidence in lowering LDL or in ezetimibe? N Engl J Med 2008; 358:1504-1507.