title: Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin.
abstract: BACKGROUND
  In the setting of stable coronary artery disease (CAD), it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alone.
  
  
  OBJECTIVE
  We sought to compare the anti-inflammatory and antiplatelet effects of ezetimibe 10mg/simvastatin 20mg (E10/S20) with simvastatin 80 mg (S80).
  
  
  RESULTS
  CAD patients (n=83, 63 ± 9 years, 57% men) receiving S20, were randomly allocated to receive E10/S20 or S80, for 6 weeks. Lipids, inflammatory markers (C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, soluble CD40 ligand and oxidized LDL), and platelet aggregation (platelet function analyzer [PFA]-100) changes were determined. Baseline lipids, inflammatory markers and PFA-100 were similar between groups. After treatment, E10/S20 and S80 patients presented, respectively: (1) similar reduction in LDL-C (29 ± 13% vs. 28 ± 30%, p=0.46), apo-B (18 ± 17% vs. 22 ± 15%, p=0.22) and oxidized LDL (15 ± 33% vs. 18 ± 47%, p=0.30); (2) no changes in inflammatory markers; and, (3) a higher increase of the PFA-100 with E10/S20 than with S80 (27 ± 43% vs. 8 ± 33%, p=0.02).
  
  
  CONCLUSIONS
  These data suggest that among stable CAD patients treated with S20, (1) both E10/S20 and S80 were equally effective in further reducing LDL-C; (2) neither treatment had any further significant anti-inflammatory effects; and (3) E10/S20 was more effective than S80 in inhibiting platelet aggregation. Thus, despite similar lipid lowering and doses 4× less of simvastatin, E10/S20 induced a greater platelet inhibitory effect than S80.
authors.affiliation: Heart Institute, University of Sao Paulo, Av. Enéas de C. Aguiar, 44, Building II, 2nd Floor, Room 12, Sao Paulo, SP 05403-901, Brazil. eduardopesaro@hotmail.com
authors.forename: Antonio Eduardo P
authors.initials: AE
authors.lastname: Pesaro
authors.forename: Carlos V
authors.initials: CV
authors.lastname: Serrano
authors.forename: Juliano L
authors.initials: JL
authors.lastname: Fernandes
authors.forename: Alexandre B
authors.initials: AB
authors.lastname: Cavalcanti
authors.forename: Alexandre H
authors.initials: AH
authors.lastname: Campos
authors.forename: Herlon S
authors.initials: HS
authors.lastname: Martins
authors.forename: Raul C
authors.initials: RC
authors.lastname: Maranhão
authors.forename: James A
authors.initials: JA
authors.lastname: de Lemos
authors.forename: Heraldo P
authors.initials: HP
authors.lastname: Souza
authors.forename: José C
authors.initials: JC
authors.lastname: Nicolau
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001055:Apolipoproteins B / Q000097:blood; D001384:Azetidines / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D019821:Simvastatin / Q000008:administration & dosage*
chemical_list: D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D001384:Azetidines; D015415:Biomarkers; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D019821:Simvastatin; D000069438:Ezetimibe