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Cardiovascular disease (CVD) is the leading cause of death worldwide, and its prevalence is expected to increase further, which will be associated with a substantial economic burden. High-risk or vulnerable plaques and, indirectly, the burden of atherosclerotic disease, are responsible for most major cardiovascular events. Most of the current prevention strategies are focused on identifying and managing the established risk factors (smoking, hypertension, hypercholesterolemia, diabetes, obesity, physical inactivity) for atherosclerosis. Another opportunity for further characterizing the population at high CVD risk would be to measure the occurrence and progression of subclinical (asymptomatic) atherosclerotic burden. The detection of subclinical atherosclerosis and high-risk plaques, if proven to predict cardiovascular events, may enable the establishment of earlier control of CVD risk factors and help preventing CVD. In this Review, we address the potential progress in CVD prevention brought about by the use of noninvasive imaging techniques to identify subclinical atherosclerosis.

Ezetimibe is a lipid-lowering drug that inhibits the intestinal absorption of dietary and biliary cholesterol by blocking passage across the intestinal wall. The efficacy and safety of adding ezetimibe to ongoing statin therapy in patients with primary hypercholesterolemia was evaluated in a randomized, double-blind, placebo-controlled study. The study group included 769 adults (aged > or =18 years) with primary hypercholesterolemia who had not achieved National Cholesterol Education Program (NCEP) Adult Treatment Panel II goals with dietary alteration and statin monotherapy. Patients receiving a stable dose of a statin for > or =6 weeks were randomized to receive concurrent treatment with placebo (n = 390) or ezetimibe (n = 379), 10 mg/day, in addition to continuing their open-label statin for 8 weeks. The primary efficacy variable was the percent change in low-density lipoprotein (LDL) cholesterol from baseline with statin monotherapy to end point after intervention (secondary variables: high-density lipoprotein [HDL] cholesterol and triglycerides). Ongoing statin therapy plus ezetimibe led to changes of -25.1% for LDL cholesterol (HDL cholesterol +2.7%; triglycerides -14.0%) compared with LDL cholesterol -3.7% (p <0.001), HDL cholesterol +1.0% (p <0.05), and triglycerides -2.9% (p <0.001) for placebo added to ongoing statin therapy. Among patients not at LDL cholesterol goal at on-statin baseline, 71.5% receiving statin plus ezetimibe versus 18.9% receiving statin plus placebo reached goal at end point (odds ratio 23.7; p <0.001). The co-administration of statin and ezetimibe was generally well tolerated. Adding ezetimibe to ongoing statin therapy led to substantial additional reduction in LDL cholesterol levels, facilitating attainment of NCEP goals. Ezetimibe offers a new therapeutic option for patients receiving statins who require further reduction in LDL cholesterol.