title: Most appropriate animal models to study the efficacy of statins: a systematic review.
abstract: BACKGROUND
  In animal models and clinical trials, statins are reported as effective in reducing cholesterol levels and lowering the risk of cardiovascular diseases. We have aggregated the findings in animal models - mice, rats and rabbits - using the technique of systematic review and meta-analysis to highlight differences in the efficacy of statins.
  
  
  METHODS
  We searched Medline and Embase. After examining all eligible articles, we extracted results about total cholesterol and other blood parameters, blood pressure, myocardial infarction and survival. Weighted and standard mean difference random effects meta-analysis was used to measure overall efficacy in prespecified species, strains and subgroups.
  
  
  RESULTS
  We included in systematic review 161 animal studies and we analysed 120 studies, accounting for 2432 animals. Statins lowered the total cholesterol across all species, although with large differences in the effect size: -30% in rabbits, -20% in mice and -10% in rats. The reduction was larger in animals fed on a high-cholesterol diet. Statins reduced infarct volume but did not consistently reduce the blood pressure or effect the overall survival. Few studies considered strains at high risk of cardiovascular diseases or hard outcomes.
  
  
  CONCLUSIONS
  Although statins showed substantial efficacy in animal models, few preclinical data considered conditions mimicking human pathologies for which the drugs are clinically indicated and utilized. The empirical finding that statins are more effective in lowering cholesterol derived from an external source (i.e. diet) conflicts with statin's supposed primary mechanism of action.
authors: Clinical Epidemiology Unit, IRCCS Orthopedic Institute Galeazzi, Milan, Italy.
authors: Valentina
authors: V
authors: Pecoraro
authors: Lorenzo
authors: L
authors: Moja
authors: Luigi
authors: L
authors: Dall'Olmo
authors: Glauco
authors: G
authors: Cappellini
authors: Silvio
authors: S
authors: Garattini
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051379:Mice; D009203:Myocardial Infarction / Q000517:prevention & control; D011817:Rabbits; D051381:Rats; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; D002784:Cholesterol
keywords: Animal models; hydroxymethylglutaryl-CoA reductase inhibitors; meta-analysis; statins; translational medical research