Statins, on the other hand, have little effect on HDL. Given the risk for adverse cardiovascular events that remains despite statin treatment,142,151 several research groups have focused their attention on the evaluation of therapies to increase HDL and to possibly improve clinical outcomes in patents already treated with preventative medications.143 147 Many clinical trials have confirmed that HDL levels can be increased through pharmacological intervention, including the use of niacin,143,144,154,155 fenofi- Although some studies have demonstrated modest biological effects such as the reduction of either carotid artery intimal thickness144,154 or angiographic the majority of the studies in the field have produced negative clinical results.143,145,155,159,160 Focusing on non-CABG populations, 2 large, placebo- controlled, clinical trials have evaluated the use of fenofi- brate therapy for the prevention of cardiac events in patients with diabetes mellitus. Fenofibrate, with or without concur- rent statin therapy, led to significant increases in HDL levels in both studies but failed to significantly reduce the primary clinical end points of fatal or nonfatal MI in either trial.159,160 Most recently, 2 large clinical trials received much atten- tion by evaluating the impact of niacin treatment to reduce vascular events among statin-treated patients with well- controlled LDL levels. In Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes (AIM-HIGH), 3414 patients with a history of cardiovascular disease were ran- domized to receive high-dose extended-release niacin or placebo. Niacin increased HDL levels by 20% but failed to reduce the rate of cardiovascular events over the 5-year trial duration (5.8% versus 5.6%, niacin versus placebo; P=NS). 