title: Ezetimibe + simvastatin versus doubling the dose of simvastatin in high cardiovascular risk diabetics: a multicenter, randomized trial (the LEAD study).
abstract: BACKGROUND
  The primary goal of therapy in patients with hypercholesterolemia and coronary heart disease (CHD) is reducing low-density lipoprotein cholesterol (LDL-C). This was a multicenter, randomized, double-blind, double-dummy study in patients with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  Adult patients with T2DM and CHD (N = 93) on a stable dose of simvastatin 20 mg with LDL-C >or= 2.6 mmol/L (100 mg/dL) and <or= 4.1 mmol/L (160 mg/dL) were randomized to ezetimibe 10 mg plus simvastatin 20 mg (EZ + simva 10/20 mg) or simvastatin 40 mg for 6 weeks. Percent change in LDL-C, high-density lipoprotein cholesterol, and triglycerides was assessed.
  
  
  RESULTS
  EZ + simva 10/20 mg produced a significantly greater change from treated baseline compared with simvastatin 40 mg in LDL-C (-32.2% vs -20.8%; p < 0.01) and total cholesterol (-20.6% vs -13.2%; p < 0.01). A greater proportion of patients achieved LDL-C < 2.6 mmol/L with EZ + simva 10/20 mg than with simvastatin 40 mg, but this was not statistically significant (78.4% vs 60%; odds ratio = 2.81; p = 0.052). Changes in high-density lipoprotein cholesterol and triglycerides were similar between treatments. Both treatments were generally well-tolerated.
  
  
  CONCLUSIONS
  These results demonstrate that EZ + simva 10/20 mg may provide a superior alternative for LDL-C lowering vs doubling the dose of simvastatin to 40 mg in hyperlipidemic patients with T2DM and CHD. In addition, the combination therapy may provide an alternative treatment for patients who require further LDL-C reduction than they can achieve with simvastatin 20 mg alone.
authors.affiliation: Department of Clinical Pathophysiology, University of Florence, Florence, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Bardini
authors.forename: Carlo B
authors.initials: CB
authors.lastname: Giorda
authors.forename: Antonio E
authors.initials: AE
authors.lastname: Pontiroli
authors.forename: Cristina
authors.initials: C
authors.lastname: Le Grazie
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Rotella
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001384:Azetidines / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D007558:Italy; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D019821:Simvastatin / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D014280:Triglycerides; C517652:hemoglobin A1c protein, human