Abstract
Importance of the field: Elevated concentrations of low-density lipoprotein (LDL) cholesterol are associated with increased risk of coronary atherosclerosis, and morbidity and mortality from coronary heart disease (CHD). Lowering of LDL cholesterol leads to a reduction in cardiovascular morbidity and all-cause mortality in individuals at risk for cardiovascular events and patients with established CHD. The mainstays of lipid lowering therapy today are the HMG-CoA reductase inhibitors (statins); however, the residual risk of cardiovascular events amongst individuals treated with statins remains a major healthcare concern.Areas covered in this review: Emerging targets for lipid lowering therapy target pathways that regulate lipoprotein assembly, lipoprotein clearance and pro-atherogenic lipoprotein modification. These emerging drugs have novel mechanisms that include inhibition of lipoprotein assembly (antisense mRNA inhibitors of apolipoprotein B and microsomal transfer protein inhibitors), enhanced lipoprotein clearance (proprotein convertase subtilisin kexin type 9, thyroid hormone analogues), inhibition of pro-atherogenic lipoprotein remodeling (cholesterol ester transfer protein inhibitors (dalcetrapib, anacetrapib) and peroxisome proliferator activator agents (GFT-505, aleglitazar)) and inhibition of lipoprotein modification (heme oxygenase-1 inhibitor (succinobucol), phospholipase A2 inhibitors (varespladib, darapladib)).What the reader will gain: A review of the most recent data on emerging drugs in the treatment of hyperlipidemia.Take home message: With these medications, we will achieve more effective reductions in cardiovascular morbidity and mortality than achieved with current lipid lowering therapies.
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