ESPITE HIGHLY EFFECTIVEcontemporary treatment regimens, the majority of vascular events are not prevented, particularly in high-risk individuals. 1,2 Therefore, further strategies to decrease atherosclerosis burden and improve cardiovascular outcomes are needed. There is a strong inverse association between high-density lipoprotein (HDL) cholesterol and risk of coronary heart disease in epidemiological studies. 3,4 Efforts to increase HDL cholesterol levels have included administration of oral compounds that interfere with lipid metabolic pathways and result in sustained increase in HDL levels over time or short-term infusion of reconstituted HDL to take advantage of its potent biological properties. 5 A provocative clinical study has suggested that short-term infusions of HDL containing a naturally occurring variant of apolipoprotein A-I (Milano) can induce regression of coronary atherosclerosis. 6 However, interpretation of Author Affiliations are listed at the end of this article. Investigators of the Effect of rHDL on Atherosclerosis-Safety and Efficacy (ERASE) Trial are listed at the end of this article.

Background-Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may prevent excess accumulation of cholesteryl esters in macrophages. The ACAT inhibitor avasimibe was shown to reduce experimental atherosclerosis. This study was designed to investigate the effects of avasimibe on human coronary atherosclerosis. Methods and Results-This randomized, double-blind, placebo-controlled trial assessed the effects of avasimibe at dosages of 50, 250, and 750 mg QD on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients received background lipid-lowering therapy if necessary to reach a target baseline LDL level Ͻ125 mg/dL (3.2 mmol/L). IVUS and coronary angiography were performed at baseline and repeated after up to 24 months of treatment. Approximately equal percentages of patients across groups received concurrent statin therapy (87% to 89%). The mean total plaque volume at baseline was Ϸ200 mm 3 , and the least squares mean change at end of treatment was 0.7 mm 3 for placebo and 7.7, 4.1, and 4.8 mm 3 for the avasimibe 50, 250, and 750 mg groups, respectively (adjusted Pϭ0.17 [unadjusted Pϭ0.057], 0.37, and 0.37, respectively). Percent atheroma volume increased by 0.4% with placebo and by 0.7%, 0.8%, and 1.0% in the respective avasimibe groups (PϭNS). LDL cholesterol increased during the study by 1.7% with placebo but by 7.8%, 9.1%, and 10.9% in the respective avasimibe groups (PϽ0.05 in all groups). Conclusions-Avasimibe did not favorably alter coronary atherosclerosis as assessed by IVUS. This ACAT inhibitor also caused a mild increase in

Inclacumab appears to reduce myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction. (A Study of RO4905417 in Patients With Non ST-Elevation Myocardial Infarction [Non-STEMI] Undergoing Percutaneous Coronary Intervention; NCT01327183).

Abstract-Cardiovascular biomarker research efforts have resulted in the identification of new risk factors and novel drug targets, as well as the establishment of treatment guidelines. Government agencies, academic research institutions, diagnostic industries, and pharmaceutical companies all recognize the importance of biomarkers in advancing therapies to improve public health. In drug development, biomarkers are used to evaluate early signals of efficacy and safety, to select dose, and to identify the target population. The United States Food and Drug Administration has relied on biomarkers to support clinical applications in many therapeutic fields, including cardiovascular disease. The appropriate application of cardiovascular biomarkers requires an understanding of disease natural history, the mechanism of the intervention, and the characteristics and limitations of the biomarker. Channels of communication among researcher, developer, and regulator must remain open to maximize the success of future biomarker efforts. In