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Effects of ezetimibe/simvastatin on lipoprotein subfractions in patients with primary hypercholesterolemia: an exploratory analysis of archived samples using two commercially available techniques.
Clin Ther 2007; 29(11):2419-32CT

Abstract

BACKGROUND

Cholesterol-rich lipoproteins, including low-density lipoprotein cholesterol (LDL-C), intermediate-density lipoprotein cholesterol (IDL-C), and very-low-density lipoprotein cholesterol (VLDL-C), are known to promote atherosclerosis. Ezetimibe/simvastatin (E/S) is an efficacious lipid-lowering treatment that inhibits both the intestinal absorption and biosynthesis of cholesterol.

OBJECTIVE

The aim of the current analysis was to compare the effects of ezetimibe and simvastatin monotherapy and E/S treatment on lipoprotein subfractions and LDL particle size in patients with primary hypercholesterolemia.

METHODS

This was an exploratory (hypothesis generating) analysis of archived plasma samples drawn from patients in a multicenter, randomized, double-blind, placebo-controlled, parallel-arm study. After a washout and diet/placebo run-in, patients with hypercholesterolemia (LDL-C, > or =145- < or =250 mg/dL; triglycerides, < or =350 mg/dL) were randomized equally to 1 of 10 daily treatments for 12 weeks: E/S (10/10, 10/20, 10/40, or 10/80 mg), simvastatin monotherapy (10, 20, 40, or 80 mg), ezetimibe monotherapy (10 mg), or placebo. A subset of patients had lipid subfraction measurements taken at baseline (week 0) and postrandomization (week 12). Plasma samples were used to quantify cholesterol associated with VLDL subfractions (VLDLI+2 and VLDL3), IDL, and 4 LDL subfractions (LDL1-4) via the Vertical Auto Profile II method. LDL-C particle size was determined using segmented gradient gel electrophoresis. The primary end point was median percent change in subfraction cholesterol for E/S versus ezetimibe or simvastatin monotherapy, pooled across doses.

RESULTS

Of the 1528 patients randomized in the original study, 1397 (91%) had lipid subfraction measurements taken. E/S was associated with significant reductions in VLDL-CI+2, VLDL-C3, IDL-C, LDL-C1, LDL-C2, and LDL-C3 versus ezetimibe, simvastatin, and placebo. E/S resulted in near-additive reductions in VLDL-CI+2, VLDL-C3, IDL-C, LDL-C1, LDL-C2, and LDL-C3 versus ezetimibe and simvastatin monotherapy. Of the subfractions examined, with regard to E/S, the greatest reductions were observed in IDL-C and LDL-C1, LDL-C2, and LDL-C3. When compared with placebo, ezetimibe, simvastatin, and E/S did not shift the distribution of LDL particles toward a larger, more buoyant LDL subclass pattern.

CONCLUSION

E/S was more effective than ezetimibe and simvastatin monotherapy in reducing atherogenic lipoprotein subfractions in these patients with primary hypercholesterolemia.

Authors+Show Affiliations

Lipid Clinic, Medical Department, Rikshospitalet, Oslo, Norway. leiv.ose@rikshospitalet.noNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18158082

Citation

Ose, Leiv, et al. "Effects of Ezetimibe/simvastatin On Lipoprotein Subfractions in Patients With Primary Hypercholesterolemia: an Exploratory Analysis of Archived Samples Using Two Commercially Available Techniques." Clinical Therapeutics, vol. 29, no. 11, 2007, pp. 2419-32.
Ose L, Reyes R, Johnson-Levonas AO, et al. Effects of ezetimibe/simvastatin on lipoprotein subfractions in patients with primary hypercholesterolemia: an exploratory analysis of archived samples using two commercially available techniques. Clin Ther. 2007;29(11):2419-32.
Ose, L., Reyes, R., Johnson-Levonas, A. O., Sapre, A., Tribble, D. L., & Musliner, T. (2007). Effects of ezetimibe/simvastatin on lipoprotein subfractions in patients with primary hypercholesterolemia: an exploratory analysis of archived samples using two commercially available techniques. Clinical Therapeutics, 29(11), pp. 2419-32.
Ose L, et al. Effects of Ezetimibe/simvastatin On Lipoprotein Subfractions in Patients With Primary Hypercholesterolemia: an Exploratory Analysis of Archived Samples Using Two Commercially Available Techniques. Clin Ther. 2007;29(11):2419-32. PubMed PMID: 18158082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of ezetimibe/simvastatin on lipoprotein subfractions in patients with primary hypercholesterolemia: an exploratory analysis of archived samples using two commercially available techniques. AU - Ose,Leiv, AU - Reyes,Robert, AU - Johnson-Levonas,Amy O, AU - Sapre,Aditi, AU - Tribble,Diane L, AU - Musliner,Thomas, PY - 2007/07/02/accepted PY - 2007/12/26/pubmed PY - 2008/2/21/medline PY - 2007/12/26/entrez SP - 2419 EP - 32 JF - Clinical therapeutics JO - Clin Ther VL - 29 IS - 11 N2 - BACKGROUND: Cholesterol-rich lipoproteins, including low-density lipoprotein cholesterol (LDL-C), intermediate-density lipoprotein cholesterol (IDL-C), and very-low-density lipoprotein cholesterol (VLDL-C), are known to promote atherosclerosis. Ezetimibe/simvastatin (E/S) is an efficacious lipid-lowering treatment that inhibits both the intestinal absorption and biosynthesis of cholesterol. OBJECTIVE: The aim of the current analysis was to compare the effects of ezetimibe and simvastatin monotherapy and E/S treatment on lipoprotein subfractions and LDL particle size in patients with primary hypercholesterolemia. METHODS: This was an exploratory (hypothesis generating) analysis of archived plasma samples drawn from patients in a multicenter, randomized, double-blind, placebo-controlled, parallel-arm study. After a washout and diet/placebo run-in, patients with hypercholesterolemia (LDL-C, > or =145- < or =250 mg/dL; triglycerides, < or =350 mg/dL) were randomized equally to 1 of 10 daily treatments for 12 weeks: E/S (10/10, 10/20, 10/40, or 10/80 mg), simvastatin monotherapy (10, 20, 40, or 80 mg), ezetimibe monotherapy (10 mg), or placebo. A subset of patients had lipid subfraction measurements taken at baseline (week 0) and postrandomization (week 12). Plasma samples were used to quantify cholesterol associated with VLDL subfractions (VLDLI+2 and VLDL3), IDL, and 4 LDL subfractions (LDL1-4) via the Vertical Auto Profile II method. LDL-C particle size was determined using segmented gradient gel electrophoresis. The primary end point was median percent change in subfraction cholesterol for E/S versus ezetimibe or simvastatin monotherapy, pooled across doses. RESULTS: Of the 1528 patients randomized in the original study, 1397 (91%) had lipid subfraction measurements taken. E/S was associated with significant reductions in VLDL-CI+2, VLDL-C3, IDL-C, LDL-C1, LDL-C2, and LDL-C3 versus ezetimibe, simvastatin, and placebo. E/S resulted in near-additive reductions in VLDL-CI+2, VLDL-C3, IDL-C, LDL-C1, LDL-C2, and LDL-C3 versus ezetimibe and simvastatin monotherapy. Of the subfractions examined, with regard to E/S, the greatest reductions were observed in IDL-C and LDL-C1, LDL-C2, and LDL-C3. When compared with placebo, ezetimibe, simvastatin, and E/S did not shift the distribution of LDL particles toward a larger, more buoyant LDL subclass pattern. CONCLUSION: E/S was more effective than ezetimibe and simvastatin monotherapy in reducing atherogenic lipoprotein subfractions in these patients with primary hypercholesterolemia. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/18158082/Effects_of_ezetimibe/simvastatin_on_lipoprotein_subfractions_in_patients_with_primary_hypercholesterolemia:_an_exploratory_analysis_of_archived_samples_using_two_commercially_available_techniques_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(07)00328-1 DB - PRIME DP - Unbound Medicine ER -