title: Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients.
abstract: OBJECTIVE
  To investigate the effects on cardiovascular outcomes of drug interventions that increase high density lipoprotein levels.
  
  
  METHODS
  Meta-analysis.
  
  
  METHODS
  Therapeutic benefit of niacin, fibrates, and cholesteryl ester transfer protein (CETP) inhibitors on cardiovascular events (all cause mortality, coronary heart disease mortality, non-fatal myocardial infarction, and stroke).
  
  
  RESULTS
  117,411 patients were randomised in a total of 39 trials. All interventions increased the levels of high density lipoprotein cholesterol. No significant effect was seen on all cause mortality for niacin (odds ratio 1.03, 95% confidence interval 0.92 to 1.15, P=0.59), fibrates (0.98, 0.89 to 1.08, P=0.66), or CETP inhibitors (1.16, 0.93 to 1.44, P=0.19); on coronary heart disease mortality for niacin (0.93, 0.76 to 1.12, P=0.44), fibrates (0.92, 0.81 to 1.04, P=0.19), or CETP inhibitors (1.00, 0.80 to 1.24, P=0.99); or on stroke outcomes for niacin (0.96, 0.75 to 1.22, P=0.72), fibrates (1.01, 0.90 to 1.13, P=0.84), or CETP inhibitors (1.14, 0.90 to 1.45, P=0.29). In studies with patients not receiving statins (before the statin era), niacin was associated with a significant reduction in non-fatal myocardial infarction (0.69, 0.56 to 0.85, P=0.0004). However, in studies where statins were already being taken, niacin showed no significant effect (0.96, 0.85 to 1.09, P=0.52). A significant difference was seen between these subgroups (P=0.007). A similar trend relating to non-fatal myocardial infarction was seen with fibrates: without statin treatment (0.78, 0.71 to 0.86, P<0.001) and with all or some patients taking statins (0.83, 0.69 to 1.01, P=0.07); P=0.58 for difference.
  
  
  CONCLUSIONS
  Neither niacin, fibrates, nor CETP inhibitors, three highly effective agents for increasing high density lipoprotein levels, reduced all cause mortality, coronary heart disease mortality, myocardial infarction, or stroke in patients treated with statins. Although observational studies might suggest a simplistic hypothesis for high density lipoprotein cholesterol, that increasing the levels pharmacologically would generally reduce cardiovascular events, in the current era of widespread use of statins in dyslipidaemia, substantial trials of these three agents do not support this concept.
authors.affiliation: International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London W2 1LA, UK drkeene@doctors.org.uk.
authors.forename: Daniel
authors.initials: D
authors.lastname: Keene
authors.affiliation: International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London W2 1LA, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Price
authors.affiliation: International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London W2 1LA, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Shun-Shin
authors.affiliation: International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London W2 1LA, UK.
authors.forename: Darrel P
authors.initials: DP
authors.lastname: Francis
mesh_terms: D000577:Amides; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D003327:Coronary Disease / Q000097:blood / Q000401:mortality / Q000517:prevention & control; D004952:Esters; D058607:Fibric Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008075:Lipoproteins, HDL / Q000097:blood*; D009203:Myocardial Infarction / Q000097:blood / Q000401:mortality / Q000517:prevention & control; D009525:Niacin / Q000627:therapeutic use*; D023303:Oxazolidinones / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000097:blood / Q000401:mortality / Q000517:prevention & control; D013438:Sulfhydryl Compounds / Q000627:therapeutic use
chemical_list: D000577:Amides; D000924:Anticholesteremic Agents; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D004952:Esters; D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D023303:Oxazolidinones; D011804:Quinolines; D013438:Sulfhydryl Compounds; D009525:Niacin; C411602:dalcetrapib; C483909:torcetrapib; C530884:anacetrapib