Effect of coadministration of ezetimibe and simvastatin on high-sensitivity C-reactive protein.
This study assessed the effect of ezetimibe coadministered with simvastatin on high-sensitivity C-reactive protein (hs-CRP) in patients with primary hypercholesterolemia. After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol > or =145 and < or =250 mg/dl and triglycerides < or =350 mg/dl were randomized to one of these daily treatments for 12 consecutive weeks: ezetimibe 10 mg; simvastatin monotherapy (10, 20, 40, or 80 mg); ezetimibe 10 mg plus simvastatin (10, 20, 40, or 80 mg); or placebo. The primary analysis was the change in hs-CRP for the pooled ezetimibe plus simvastatin versus simvastatin monotherapy groups. Ezetimibe plus simvastatin significantly reduced median hs-CRP levels compared with simvastatin monotherapy (-34.8% vs -18.2%, p<0.01), and incremental reductions were observed at each simvastatin dose level. Combination therapy-induced significant changes in individual lipid parameters did not explain the observed decreases in hs-CRP. Thus, ezetimibe coadministered with simvastatin resulted in significant incremental decreases in hs-CRP, possibly consistent with an additional anti-inflammatory effect compared with simvastatin monotherapy.
Sager
Philip T
PT
Schering-Plough Research Institute, Kenilworth, New Jersey 07033-1300, USA. Philip.Sager@spcorp.com
Melani
Lorenzo
L
Lipka
Leslie
L
Strony
John
J
Yang
Bo
B
Suresh
Ramachandran
R
Veltri
Enrico
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001055:Apolipoproteins B / Q000097:blood; D001384:Azetidines / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000032:analysis / Q000187:drug effects*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D001384:Azetidines; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; D002097:C-Reactive Protein; D019821:Simvastatin; D000069438:Ezetimibe