title: Baseline cholesterol absorption and the response to ezetimibe/simvastatin therapy: a post-hoc analysis of the ENHANCE trial.
abstract: Subjects with increased cholesterol absorption might benefit more from statin therapy combined with a cholesterol absorption inhibitor. We assessed whether baseline cholesterol absorption markers were associated with response to ezetimibe/simvastatin therapy, in terms of LDL-cholesterol (LDL-C) lowering and cholesterol absorption inhibition, in patients with familial hypercholesterolemia (FH). In a posthoc analysis of the two-year ENHANCE trial, we assessed baseline cholesterol-adjusted campesterol (campesterol/TC) and sitosterol/TC ratios in 591 FH patients. Associations with LDL-C changes and changes in cholesterol absorption markers were evaluated by multiple regression analysis. No association was observed between baseline markers of cholesterol absorption and the extent of LDL-C response to ezetimibe/simvastatin therapy (beta = 0.020, P = 0.587 for campesterol/TC and beta<0.001, P = 0.992 for sitosterol/TC). Ezetimibe/simvastatin treatment reduced campesterol levels by 68% and sitosterol levels by 62%; reductions were most pronounced in subjects with the highest cholesterol absorption markers at baseline, the so-called high absorbers (P < 0.001). Baseline cholesterol absorption status does not determine LDL-C lowering response to ezetimibe/simvastatin therapy in FH, despite more pronounced cholesterol absorption inhibition in high absorbers. Hence, these data do not support the use of baseline absorption markers as a tool to determine optimal cholesterol lowering strategy in FH patients. However, due to the exploratory nature of any posthoc analysis, these results warrant further prospective evaluation in different populations.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Jakulj
authors.forename: M N
authors.initials: MN
authors.lastname: Vissers
authors.forename: A K
authors.initials: AK
authors.lastname: Groen
authors.forename: B A
authors.initials: BA
authors.lastname: Hutten
authors.forename: D
authors.initials: D
authors.lastname: Lutjohann
authors.forename: E P
authors.initials: EP
authors.lastname: Veltri
authors.forename: J J P
authors.initials: JJ
authors.lastname: Kastelein
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000145:classification / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000097:blood; D019821:Simvastatin / Q000627:therapeutic use*; D012855:Sitosterols / Q000097:blood; D013223:Statistics as Topic
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D015415:Biomarkers; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010840:Phytosterols; D012855:Sitosterols; C021273:campesterol; C025473:gamma-sitosterol; C001521:lathosterol; D002784:Cholesterol; D019821:Simvastatin; D000069438:Ezetimibe