Influence of metabolic syndrome factors and insulin resistance on the efficacy of ezetimibe/simvastatin and atorvastatin in patients with metabolic syndrome and atherosclerotic coronary heart disease risk.
BACKGROUND
Metabolic syndrome (MetS) and insulin resistance (IR) are increasing in prevalence, are associated with higher risk for coronary heart disease (CHD), and may potentially influence the responses to lipid-altering drug therapy. This study evaluated the effects of MetS factors (abdominal obesity, depleted high-density lipoprotein cholesterol [HDL-C], and elevated triglycerides, blood pressure, and fasting glucose) and IR on ezetimibe/simvastatin and atorvastatin treatment efficacy in patients with MetS.


METHODS
This post-hoc analysis of a multicenter, 6-week, double-blind, randomized, parallel group study of 1128 subjects with hypercholesterolemia, MetS, and moderately high/high CHD risk evaluated the effects of baseline MetS factors/IR on percent change from baseline in lipids, apolipoproteins, and high-sensitivity C-reactive protein (hs-CRP), after treatment with the usual starting doses of ezetimibe/simvastatin (10/20 mg) versus atorvastatin (10 mg, 20 mg) and next higher doses (10/40 mg versus 40 mg).


RESULTS
Ezetimibe/simvastatin and atorvastatin efficacy was generally consistent across MetS factor/IR subgroups. Ezetimibe/simvastatin produced greater incremental percent reductions in LDL-C, non-HDL-C, apolipoprotein B, total cholesterol, and lipoprotein ratios for all subgroups, and larger percent increases in HDL-C and apolipoprotein AI for all but non-obese and HDL-C ≥ 40 mg/dL subgroups than atorvastatin at the doses compared. Triglycerides, very-LDL-C, and hs-CRP results were more variable but similar between treatment groups.


CONCLUSIONS
The magnitude of lipid-altering effects produced by each treatment regimen was generally similar across all MetS and IR subgroups. Ezetimibe/simvastatin produced greater percent reductions in most lipid fractions than atorvastatin at the dose comparisons studied, and all treatments were generally well tolerated. (Registered at clinicaltrials.gov: NCT00409773).
Clinical Research of South Florida, Coral Gables, FL, USA. jrosen@crsouthflorida.com.
Jeffrey B
JB
Rosen
Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. cmb@bcm.tmc.edu.
Christie M
CM
Ballantyne
Wexner Medical Center, The Ohio State University, Columbus, Ohio, USA. willa.hsueh@osumc.edu.
Willa A
WA
Hsueh
Merck & Co., Inc., Kenilworth, NJ, USA. jianxin_lin@merck.com.
Jianxin
J
Lin
Merck & Co., Inc., Kenilworth, NJ, USA. arvind_shah@merck.com.
Arvind K
AK
Shah
Merck & Co., Inc., Kenilworth, NJ, USA. lowero12@verizon.net.
Robert S
RS
Lowe
Merck & Co., Inc., Kenilworth, NJ, USA. andrew_tershakovec@merck.com.
Andrew M
AM
Tershakovec
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000473:pathology; D003327:Coronary Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D000069438:Ezetimibe / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007333:Insulin Resistance; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood / Q000150:complications / Q000473:pathology; D012307:Risk Factors; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001786:Blood Glucose; D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL; D014280:Triglycerides; D002097:C-Reactive Protein; D000069059:Atorvastatin; D019821:Simvastatin; D000069438:Ezetimibe