title: Comparative efficacy of the addition of ezetimibe to statin vs statin titration in patients with hypercholesterolaemia: systematic review and meta-analysis.
abstract: OBJECTIVE
  To systematically review and analyse evidence for cholesterol-lowering efficacy of at least 4 weeks of add-on ezetimibe vs doubling statin dose, in adults with primary hypercholesterolaemia.
  
  
  METHODS
  MEDLINE, EMBASE and Cochrane databases were searched to identify randomised controlled trials of ezetimibe-statin combination vs statin titration (January 1993 - March 2010). Studies were selected using predefined criteria. Two reviewers conducted screening of articles, critical appraisal and data extraction; a third reviewer resolved disagreements. The difference between treatments was analysed for four co-primary outcomes: mean percentage change from baseline in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC); and proportion of patients achieving LDL-C treatment goal. Data were combined by two sets of direct comparison fixed and random effects meta-analysis: (1) compared data in the same treatment period between groups; (2) compared the incremental change in lipid levels of add-on ezetimibe vs doubling statin dose. Heterogeneity was assessed using the I(2) statistic.
  
  
  RESULTS
  Thirteen studies including 5080 patients were included in the meta-analyses. Data on simvastatin, atorvastatin and rosuvastatin were analysed. Results for primary and secondary outcomes were in favour of the ezetimibe-statin combination. A significantly greater percentage reduction in LDL-C levels was achieved in patients treated with ezetimibe-statin vs statin monotherapy (weighted mean difference [WMD]: -14.1% [-16.1, -12.1], p < 0.001). Reduction in LDL-C levels attributed to add-on ezetimibe was significantly greater than that for statin dose doubling (WMD: -15.3% [-19.1, -11.4], p < 0.001). Achievement of LDL-C goal favoured add-on ezetimibe over statin titration and was statistically significant (odds ratio: LDL-C treatment goal 2.45 [1.95, 3.08], p = 0.007).
  
  
  CONCLUSIONS
  Meta-analyses were restricted by the limited number of studies with similar trial design and method of statin titration. Results indicate that add-on ezetimibe is significantly more effective in reducing LDL-C levels than doubling statin dose, enabling more patients to achieve LDL-C goal.
authors.affiliation: Department of Clinical Biochemistry (Vascular Disease Prevention Clinics), University College London (UCL) Medical School, London, UK. mikhailidis@aol.com
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
authors.forename: Richard W
authors.initials: RW
authors.lastname: Lawson
authors.forename: Anna-Louise
authors.initials: AL
authors.lastname: McCormick
authors.forename: Gillian C
authors.initials: GC
authors.lastname: Sibbring
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tershakovec
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Davies
authors.forename: Kaan
authors.initials: K
authors.lastname: Tunceli
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001384:Azetidines / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy*
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe