Use of microsomal triglyceride transfer protein inhibitors in patients with homozygous familial hypercholesterolemia: translating clinical trial experience into clinical practice.
Homozygous familial hypercholesterolemia (HoFH) is associated with severe hypercholesterolemia and premature cardiovascular morbidity and mortality. The most frequent cause of HoFH is loss of function mutations in the gene for the low-density lipoprotein receptor, resulting in reduced clearance of low-density lipoprotein (LDL) cholesterol from the circulation. Patients with HoFH have attenuated responsiveness to lipidlowering therapies such as statins, cholesterol absorption inhibition, and bile acid binding resins because of impaired LDL receptor expression. Lomitapide is a novel microsomal triglyceride transfer protein inhibitor that does not depend on the ability to upregulate LDL receptors on the surface of hepatocytes. Lomitapide reduces production of apolipoprotein B-containing lipoproteins, significantly reduces serum levels of LDL cholesterol, and is approved for use in patients with HoFH in the United States and the European Union.
CGH Medical Center, Sterling, IL, and University of Illinois College of Medicine, Peoria, IL.
Peter P
PP
Toth
Division of Cardiology and Oppenheimer Atherosclerosis Research Center, Cedars Sinai Heart Institute, Los Angeles, CA.
Prediman K
PK
Shah
Michael J
MJ
Wilkinson
Department of Medicine, University of Chicago, Chicago, IL.
Michael H
MH
Davidson
St. John Providence Health System, Warren, MI, and Providence Hospitals and Medical Centers, Southfield and Novi, MI.
Peter A
PA
McCullough
D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D002986:Clinical Trials as Topic; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009154:Mutation; D011973:Receptors, LDL / Q000097:blood / Q000235:genetics*; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; C473731:BMS201038; D001562:Benzimidazoles; D015415:Biomarkers; D002352:Carrier Proteins; D008078:Cholesterol, LDL; C573412:LDLR protein, human; D011973:Receptors, LDL; C106092:microsomal triglyceride transfer protein