Novel Therapies for Low-Density Lipoprotein Cholesterol Reduction.
Although many clinical trials and meta-analyses have demonstrated that lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with proportionately greater reductions in the risk of cardiovascular disease events, not all patients with hypercholesterolemia are able to attain risk-stratified LDL-C goals with statin monotherapy. Elucidation of the pathophysiology of genetic disorders of lipid metabolism (e.g., familial hypercholesterolemia) has led to the development of several novel lipid-lowering strategies, including blocking the degradation of hepatic LDL-C receptors that are important in LDL-C clearance, or the inhibition of apoprotein synthesis and lipidation. Mipomersen and lomitapide are highly efficacious new agents available for the treatment of patients with homozygous familial hypercholesterolemia. The recent introduction of PCSK9 inhibitors (alirocumab and evolocumab) have made it possible for many patients to achieve very low LDL-C concentrations (e.g., <40 mg/dl) that are usually not attainable with statin monotherapy. Ongoing clinical trials are examining the impact of very low LDL-C levels on cardiovascular disease event rates and the long-term safety of this approach.
Community General Hospital Medical Center, Sterling, Illinois; University of Illinois School of Medicine, Peoria, Illinois; Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: Peter.Toth@cghmc.com.
Peter P
PP
Toth
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy*; D009841:Oligonucleotides / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D018570:Risk Assessment; D012307:Risk Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; C473731:BMS201038; D001562:Benzimidazoles; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009841:Oligonucleotides; C524142:mipomersen; C577155:evolocumab; C571059:alirocumab