TY - JOUR
T1 - LDL-C-lowering therapy: current and future therapeutic targets
AU - Visser, Maartje E.
AU - Jakulj, Lily
AU - Kastelein, John J. P.
AU - Stroes, Erik S. G.
PY - 2008
Y1 - 2008
N2 - Recent trials have emphasized that more intensive low-density lipoprotein cholesterol (LDL-C) lowering results in a further reduction in cardiovascular disease risk. Uptitration of statins has limited incremental LDL-C-lowering effects and leads to an increased incidence of side effects. Therefore, attention has shifted toward alternative LDL-C-lowering modalities. Several promising compounds have entered the clinical trial arena, although with mixed results. Acyl-coenzyme A: cholesterol O-acyltransferase (ACAT) inhibitors failed to show benefit. Microsomal triglyceride transfer protein and squalene synthase inhibitors, in spite of beneficial lipid profile changes, have shown adverse event profiles. In contrast, inhibitors of intestinal cholesterol absorption have shown LDL-C-lowering efficacy associated with few side effects. The inhibition of apolipoprotein B100 synthesis by antisense oligonucleotides has now been tested in phase 2 clinical trials, with promising results. Finally, compounds modifying protein convertase subtilisin/kexin type 9 levels are currently in the preclinical phase. In the present article, we discuss these LDL-C-lowering strategies
AB - Recent trials have emphasized that more intensive low-density lipoprotein cholesterol (LDL-C) lowering results in a further reduction in cardiovascular disease risk. Uptitration of statins has limited incremental LDL-C-lowering effects and leads to an increased incidence of side effects. Therefore, attention has shifted toward alternative LDL-C-lowering modalities. Several promising compounds have entered the clinical trial arena, although with mixed results. Acyl-coenzyme A: cholesterol O-acyltransferase (ACAT) inhibitors failed to show benefit. Microsomal triglyceride transfer protein and squalene synthase inhibitors, in spite of beneficial lipid profile changes, have shown adverse event profiles. In contrast, inhibitors of intestinal cholesterol absorption have shown LDL-C-lowering efficacy associated with few side effects. The inhibition of apolipoprotein B100 synthesis by antisense oligonucleotides has now been tested in phase 2 clinical trials, with promising results. Finally, compounds modifying protein convertase subtilisin/kexin type 9 levels are currently in the preclinical phase. In the present article, we discuss these LDL-C-lowering strategies
M3 - Article
C2 - 18950563
SN - 1523-3782
VL - 10
SP - 512
EP - 520
JO - Current Cardiology Reports
JF - Current Cardiology Reports
IS - 6
ER -