title: Relations of change in plasma levels of LDL-C, non-HDL-C and apoB with risk reduction from statin therapy: a meta-analysis of randomized trials.
abstract: BACKGROUND
  Identifying the best markers to judge the adequacy of lipid-lowering treatment is increasingly important for coronary heart disease (CHD) prevention given that several novel, potent lipid-lowering therapies are in development. Reductions in LDL-C, non-HDL-C, or apoB can all be used but which most closely relates to benefit, as defined by the reduction in events on statin treatment, is not established.
  
  
  RESULTS
  We performed a random-effects frequentist and Bayesian meta-analysis of 7 placebo-controlled statin trials in which LDL-C, non-HDL-C, and apoB values were available at baseline and at 1-year follow-up. Summary level data for change in LDL-C, non-HDL-C, and apoB were related to the relative risk reduction from statin therapy in each trial. In frequentist meta-analyses, the mean CHD risk reduction (95% CI) per standard deviation decrease in each marker across these 7 trials were 20.1% (15.6%, 24.3%) for LDL-C; 20.0% (15.2%, 24.7%) for non-HDL-C; and 24.4% (19.2%, 29.2%) for apoB. Compared within each trial, risk reduction per change in apoB averaged 21.6% (12.0%, 31.2%) greater than changes in LDL-C (P<0.001) and 24.3% (22.4%, 26.2%) greater than changes in non-HDL-C (P<0.001). Similarly, in Bayesian meta-analyses using various prior distributions, Bayes factors (BFs) favored reduction in apoB as more closely related to risk reduction from statins compared with LDL-C or non-HDL-C (BFs ranging from 484 to 2380).
  
  
  CONCLUSIONS
  Using both a frequentist and Bayesian approach, relative risk reduction across 7 major placebo-controlled statin trials was more closely related to reductions in apoB than to reductions in either non-HDL-C or LDL-C.
authors.affiliation: Preventive and Genomic Cardiology, McGill University Health Centre, Department of Medicine, Montreal, Quebec, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Thanassoulis
authors.forename: Ken
authors.initials: K
authors.lastname: Williams
authors.forename: Keying
authors.initials: K
authors.lastname: Ye
authors.forename: Robert
authors.initials: R
authors.lastname: Brook
authors.forename: Patrick
authors.initials: P
authors.lastname: Couture
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Lawler
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Graaf
authors.forename: Curt D
authors.initials: CD
authors.lastname: Furberg
authors.forename: Allan
authors.initials: A
authors.lastname: Sniderman
mesh_terms: D001055:Apolipoproteins B / Q000097:blood*; D001499:Bayes Theorem; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D015536:Down-Regulation; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D023381:Endpoint Determination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001055:Apolipoproteins B; D015415:Biomarkers; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol
keywords: LDL‐C; apoB; meta‐analysis; non‐HDL‐C; statins
references.citation: J Lipid Res. 2007 Nov;48(11):2499-505
references.pmid: 17698856
references.citation: Mayo Clin Proc. 2013 Oct;88(10):1108-14
references.pmid: 24079680
references.citation: Circulation. 2012 May 22;125(20):2469-78
references.pmid: 22539783
references.citation: Circulation. 2000 Feb 8;101(5):477-84
references.pmid: 10662743
references.citation: Circulation. 2004 Nov 2;110(18):2824-30
references.pmid: 15492318
references.citation: J Clin Lipidol. 2012 Jul-Aug;6(4):303-9
references.pmid: 22836065
references.citation: Eur Heart J. 2012 Jul;33(13):1635-701
references.pmid: 22555213
references.citation: Circulation. 2002 Mar 12;105(10):1162-9
references.pmid: 11889008
references.citation: Can J Cardiol. 2013 Feb;29(2):151-67
references.pmid: 23351925
references.citation: Am J Cardiol. 2012 Nov 15;110(10):1468-76
references.pmid: 22906895
references.citation: Clin Chem. 1997 Dec;43(12):2364-78
references.pmid: 9439456
references.citation: Lancet. 2009 Apr 4;373(9670):1175-82
references.pmid: 19329177
references.citation: Circulation. 1998 Apr 21;97(15):1453-60
references.pmid: 9576425
references.citation: N Engl J Med. 2006 Aug 10;355(6):549-59
references.pmid: 16899775
references.citation: N Engl J Med. 1997 Jan 16;336(3):153-62
references.pmid: 8992351
references.citation: J Clin Lipidol. 2008 Feb;2(1):36-42
references.pmid: 21291713
references.citation: Clin Chem. 2012 Jan;58(1):183-9
references.pmid: 22065156
references.citation: Circulation. 2005 Nov 29;112(22):3375-83
references.pmid: 16316964
references.citation: J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2889-934
references.pmid: 24239923
references.citation: Circ Cardiovasc Qual Outcomes. 2011 May;4(3):337-45
references.pmid: 21487090
references.citation: Diabetologia. 2006 May;49(5):937-44
references.pmid: 16525840
references.citation: Lancet. 2004 Aug 21-27;364(9435):685-96
references.pmid: 15325833
references.citation: JAMA. 2012 Mar 28;307(12):1302-9
references.pmid: 22453571
references.citation: Lancet. 2010 Nov 13;376(9753):1670-81
references.pmid: 21067804