title: Increasing doses of simvastatin versus combined ezetimibe/simvastatin: effect on circulating endothelial progenitor cells.
abstract: BACKGROUND
  Patients with coronary artery disease (CAD) should be treated with statins to attain very low cholesterol levels, in order to reduce cardiovascular adverse events. More than 70% of these patients do not reach the appropriate cholesterol goal despite moderate statin doses. However, it is not known whether therapeutic uptitration with different lipid-lowering strategies has a similar "pleiotropic" effect on atherosclerotic endothelial dysfunction evaluated by measurement of endothelial progenitor cells (EPCs).
  
  
  OBJECTIVE
  We sought to compare, in patients with stable CAD and with a low-density lipoprotein cholesterol (LDL-C) >70 mg/dL on treatment with simvastatin 20 mg, the effects on EPCs by increasing simvastatin to 80 mg versus adding ezetimibe 10 mg.
  
  
  METHODS
  Patients (n = 68, 63 ± 9 years, 39% men) were randomly allocated to receive ezetimibe 10/simvastatin 20 mg or simvastatin 80 mg for 6 weeks. Circulating EPCs were measured by flow cytometry before and after the treatment.
  
  
  RESULTS
  Both strategies presented similar effects on metabolic parameters. The LDLs were equally reduced by ezetimibe 10/simvastatin 20 mg and simvastatin 80 mg (28.9% ± 13% vs 21.1% ± 33%; P = .46, respectively). The levels of EPCs were unaffected by ezetimibe 10/simvastatin 20 mg (median [25th, 75th]: pre- vs posttreatment, 7.0 [2.3; 13.3] vs 3.1 [0.1; 13.2] EPCs/10(4) mononuclear cells; P = .43) or simvastatin 80 mg (pre- vs posttreatment, 6.1 [2.9; 15.2] vs 4.0 [1.4; 10.7] EPCs/10(4) mononuclear cells; P = .5), and there were no differences between the groups on treatment effects (P = .9).
  
  
  CONCLUSIONS
  Among stable patients with CAD and with an LDL-C >70 mg/dL on simvastatin 20 mg, increasing simvastatin dose to 80 mg or adding ezetimibe 10 mg promoted similar further cholesterol reduction but did not have incremental effects on circulating EPCs. These data suggest that the effects of simvastatin moderate doses on EPCs are not increased by intensive lipid-lowering strategies (clinicaltrials.gov: NCT00474123).
authors.affiliation: Hospital Israelita Albert Einstein, Av Albert Einstein, Paulo-SP, Brazil. antonioepp@einstein.br
authors.forename: Antonio Eduardo P
authors.initials: AE
authors.lastname: Pesaro
authors.forename: Carlos V
authors.initials: CV
authors.lastname: Serrano
authors.forename: Marcelo
authors.initials: M
authors.lastname: Katz
authors.forename: Luciana
authors.initials: L
authors.lastname: Marti
authors.forename: Juliano L
authors.initials: JL
authors.lastname: Fernandes
authors.forename: Paulo R G
authors.initials: PR
authors.lastname: Parra
authors.forename: Alexandre H
authors.initials: AH
authors.lastname: Campos
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D000069499:Ezetimibe, Simvastatin Drug Combination; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin
keywords: coronary artery disease; endothelial progenitor cells; ezetimibe; simvastatin