Emerging drugs for hyperlipidemia.
BACKGROUND
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.


METHODS
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 A(2) inhibitors (varespladib, darapladib)).


RESULTS
A review of the most recent data on emerging drugs in the treatment of hyperlipidemia.


CONCLUSIONS
With these medications, we will achieve more effective reductions in cardiovascular morbidity and mortality than achieved with current lipid lowering therapies.
Paras
Christos
C
SUNY Downstate Medical Center, Brooklyn, NY, USA.
Hussain
M Mahmood
MM
Rosenson
Robert S
RS
D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D012307:Risk Factors
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents