title: Clinical benefit from pharmacological elevation of high-density lipoprotein cholesterol: meta-regression analysis.
abstract: BACKGROUND
  Epidemiological evidence that the risk of coronary heart disease is inversely associated with the level of high-density lipoprotein cholesterol (HDL-C) has motivated several phase III programmes with cholesteryl ester transfer protein (CETP) inhibitors.
  
  
  OBJECTIVE
  To assess alternative methods to predict clinical response of CETP inhibitors.
  
  
  METHODS
  Meta-regression analysis on raising HDL-C drugs (statins, fibrates, niacin) in randomised controlled trials.
  
  
  RESULTS
  51 trials in secondary prevention with a total of 167,311 patients for a follow-up >1 year where HDL-C was measured at baseline and during treatment. The meta-regression analysis showed no significant association between change in HDL-C (treatment vs comparator) and log risk ratio (RR) of clinical endpoint (non-fatal myocardial infarction or cardiac death). CETP inhibitors data are consistent with this finding (RR: 1.03; P5-P95: 0.99-1.21). A prespecified sensitivity analysis by drug class suggested that the strength of relationship might differ between pharmacological groups. A significant association for both statins (p<0.02, log RR=-0.169-0.0499*HDL-C change, R(2)=0.21) and niacin (p=0.02, log RR=1.07-0.185*HDL-C change, R(2)=0.61) but not fibrates (p=0.18, log RR=-0.367+0.077*HDL-C change, R(2)=0.40) was shown. However, the association was no longer detectable after adjustment for low-density lipoprotein cholesterol for statins or exclusion of open trials for niacin.
  
  
  CONCLUSIONS
  Meta-regression suggested that CETP inhibitors might not influence coronary risk. The relation between change in HDL-C level and clinical endpoint may be drug dependent, which limits the use of HDL-C as a surrogate marker of coronary events. Other markers of HDL function may be more relevant.
authors: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: F
authors: F
authors: Hourcade-Potelleret
authors: University Hospital of Saint-Etienne-Hospital Nord, Saint-Etienne, France.
authors: S
authors: S
authors: Laporte
authors: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: V
authors: V
authors: Lehnert
authors: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: P
authors: P
authors: Delmar
authors: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: Renée
authors: R
authors: Benghozi
authors: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: U
authors: U
authors: Torriani
authors: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors: R
authors: R
authors: Koch
authors: University Hospital of Saint-Etienne-Hospital Nord, Saint-Etienne, France.
authors: P
authors: P
authors: Mismetti
mesh_terms: D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000187:drug effects*; D003327:Coronary Disease / Q000517:prevention & control*; D058607:Fibric Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D009525:Niacin / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009525:Niacin