Current strategies and recent advances in the therapy of hypercholesterolemia

Abstract

Lipid therapy is an option for preventing atherosclerotic vascular disease that has been intensively studied and proved to be effective independent of the underlying risk factors. Since the optimal LDL-cholesterol appears to lie well below 100 mg/dl most potent lipid lowering drugs and adjunctive HDL-raising therapeutics are mandatory. Inhibition of cholesterol synthesis and absorption is currently the preferred measure. However, new developments may substantially increase the efficacy of lipid therapy. One is add-on colesevelam, a synthetic bile-acid sequestrant with increased binding affinity which allows smaller dosages for better tolerability. Alternatively HDL-cholesterol may be increased by 25% using niacin with improved tolerability due to the combination with laropiprant, an inhibitor of the receptor for prostaglandin D2-receptor, which minimizes flushing close to placebo level. Mipomersen, a specific oligonucleotide capable to reduce apolipoprotein B-100 up to 70%, is certainly the most advanced approach to challenge even apheresis as the most effective measure to lower exceptionally elevated cholesterol levels.