"Unknown" reason for EHANCE study failure

At another presentation at the 2007 American College of Cardiology conference, the authors of the ENHANCE study provided three theoretical explanations why, despite ezetimibe/simvastatin significantly lowering LDL more than simvastatin (56% versus 39%, p<0.01), there was no significant difference between treatment groups on the primary and four key secondary endpoints.

They noted that lowering of LDL cholesterol with non-statin therapy, such as ezetimibe, might affect carotid artery intima-media thickness differently than statin therapy, while the imaging technology selected was not sensitive enough to detect a difference. They also stated that the 720 patients with heterozygous familial hypercholesterolemia patients who took part in the study were extensively pre-treated with lipid-lowering therapy, thereby limiting the amount that CA IMT could change with further LDL cholesterol-lowering therapy, consequently limiting the ability to detect a differential response to the two treatments. The authors concluded that the reason for the failure to observe an incremental effect on CA IMT thickness in spite of a reduction of level of LDL cholesterol remains unknown.