title: Comparison of effects of high (80 mg) versus low (20 mg) dose of simvastatin on C-reactive protein and lipoproteins in patients with angiographic evidence of coronary arterial narrowing.
abstract: Although previous studies have demonstrated that various "statins" decrease levels of high-sensitivity C-reactive protein (hs-CRP), the dose-response relation for lowering hs-CRP by the clinically important drug simvastatin compared with lipid lowering is unclear. A 16-week, randomized, double-blind study was performed in patients with stable coronary artery disease and high hs-CRP levels (>3 mg/L). Subjects were randomized to placebo, 20 mg of simvastatin, or 80 mg of simvastatin for 12 weeks. Those currently on a statin first underwent a 4-week washout. Of the 107 total patients randomized, 96 completed the trial, and 89 were able to be evaluated for efficacy. Changes in hs-CRP differed across simvastatin and placebo groups (change score +1.6 vs -0.6 mg/L, p = 0.004), but no dose response was observed when comparing 80 with 20 mg/day (-0.6 vs -0.5 mg/L, respectively). A strong dose response was observed for changes in total (p <0.01) and low-density lipoprotein (p <0.001) cholesterol. hs-CRP changes did not correlate with low-density lipoprotein changes. In conclusion, this randomized trial in patients with chronic stable coronary artery disease showed a strong dose response for simvastatin for total and low-density lipoprotein cholesterol lowering but not for hs-CRP.
authors.affiliation: Cardiovascular Department, LDS Hospital, Division of Cardiology, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Kent G
authors.initials: KG
authors.lastname: Meredith
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Horne
authors.forename: Robert R
authors.initials: RR
authors.lastname: Pearson
authors.forename: Chloe Allen
authors.initials: CA
authors.lastname: Maycock
authors.forename: Donald L
authors.initials: DL
authors.lastname: Lappe
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Anderson
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Muhlestein
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism*; D017023:Coronary Angiography; D023921:Coronary Stenosis / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D008074:Lipoproteins / Q000097:blood* / Q000187:drug effects; D008297:Male; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D002097:C-Reactive Protein; D019821:Simvastatin