After much speculation, to the point of congressional involvement, regarding the reasons for the delay in reporting the results of a relatively small trial of carotid-artery imaging in patients with familial hypercholesterolemia (FH), a brief top-line synopsis was released this year on January 14(1). The study, called ENHANCE (Effect of Combination Ezetimibe and High-Dose Simvastatin versus Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia), was designed to determine if an anticipated additional reduction in LDL-cholesterol (LDLc) of 18% when ezetimibe 10 mg was added to 80 mg of simvastatin (Vytorin 10/80 mg) versus 80 mg simvastatin alone would result in either less progression or more regression of carotid atherosclerosis as measured by intima-media thickening (cIMT). The study was conducted over a 2-year period and enrolled 720 FH patients, with roughly equal numbers of men and women, mean age 45 years. Although patients had very high LDLc concentrations of nearly 320 mg/dL (8.32 mmol/L) after all lipid-lowering agents were washed out, more than 80% had been on prior statin treatment, including high-dose treatment, for many years before entry into the trial. The changes in cIMT after 2 years did not significantly differ from baseline for either treatment group or from one treatment group to the other. The popular press contacted selected “experts” who gave flamboyant, misleading, and sometimes self-serving or agenda-driven comments(2) interpreting the results either as a failure of the mechanism by which LDLc was decreased, or as evidence that LDLc reduction itself was not an effective way to ameliorate the course of atherosclerosis. The complete details of ENHANCE have now been published(3), and a more complete evaluation is possible. A number of critical flaws in the trial are apparent. The most important determinant of any clinical trial such as ENHANCE is the …