The prerequisites under which ‘novel’ compounds have to show cardiovascular benefit on top of statin therapy have raised the bar for clinical endpoint studies. B-mode ultrasound measurement of the carotid intima media thickness (cIMT) is the best validated imaging modality and most widely used surrogate endpoint in intervention studies to evaluate treatment efficacy in the progression of athero...

Intensive treatment of hyperlipidemia is an important factor in the prevention of cardiovascular disease. Among several therapies, statins are well recognized as playing a central role, although low density lipoprotein bound cholesterol-apheresis can be used to treat very severe cases of familial hypercholesterolemia. However, statins are not always effective on their own and, recently, ezetimi...

As health care budgets are under pressure, evaluation of cost-effectiveness is of increasing importance to provide arguments to insurance companies to pay for diagnostic procedures or for specific treatments. Methodology for cost-effectiveness analyses has been evolving over the last years but is still complex and based on various assumptions. In their study, Van Nooten et al. evaluated the cos...

Hyperlipidemia is associated with an increased risk of cardiovascular events; reducing low-density lipoprotein cholesterol (LDL-C), the primary target for cholesterol-lowering therapy, lowers the risk for such events. Although bile acid sequestrants were the first class of drugs to show a mortality benefit related to LDL-C lowering, statins are now considered first-line pharmacological therapy ...

INTRODUCTION Absorption of both dietary cholesterol and cholesterol cleared from the liver through biliary secretion contributes substantially to tight control of cholesterol homeostasis. This process is mediated by a specific transporter – Niemann-Pick C1-Like 1 (NPC1L1) protein – localized to the brush border membrane of jejunal enterocytes (Figure 1, Table 1). NPC1L1 was first described by D...

OBJECTIVE We examined the effect of ezetimibe, a cholesterol absorption (CA) inhibitor, and genetic determinants of CA on reverse cholesterol transport (RCT) from subcutaneously injected macrophages using a new dual isotope label technique. METHODS AND RESULTS Treatment of C57BL/6J mice with ezetimibe decreased dietary CA by 86% and increased RCT from peripheral tissue macrophages (PTM) by 6-...

CONTEXT Despite current standard of care, many patients at high risk of cardiovascular disease (CVD) still have elevated low-density lipoprotein cholesterol (LDL-C) levels. Alirocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9. OBJECTIVE The objective of the study was to compare the LDL-C-lowering efficacy of adding alirocumab vs other comm...

AIMS Ezetimibe reduces plasma levels of low-density lipoprotein (LDL) cholesterol by inhibiting Niemann-Pick C1-Like protein 1 (NPC1L1), the transporter responsible for cholesterol uptake from the intestine into enterocytes and from the bile into hepatocytes. We tested the hypothesis that genetic variation in NPC1L1, mimicking the effect of ezetimibe, was associated with reduced risk of ischaem...