Preventive cardiology
Meta-Analysis of Comparison of Effectiveness of Lowering Apolipoprotein B Versus Low-Density Lipoprotein Cholesterol and Nonhigh-Density Lipoprotein Cholesterol for Cardiovascular Risk Reduction in Randomized Trials

https://doi.org/10.1016/j.amjcard.2012.07.007Get rights and content

This study evaluated the relation between apolipoprotein B (apoB) decrease and coronary heart disease, stroke, and cardiovascular disease risk. Bayesian random-effects meta-analysis was used to evaluate the association of mean absolute apoB decrease (milligrams per deciliter) with relative risk of coronary heart disease (nonfatal myocardial infarction and coronary heart disease death), stroke (nonfatal stroke and fatal stroke), or cardiovascular disease (coronary heart disease, stroke, and coronary revascularization). Analysis included 25 trials (n = 131,134): 12 on statin, 4 on fibrate, 5 on niacin, 2 on simvastatin–ezetimibe, 1 on ileal bypass surgery, and 1 on aggressive versus standard low-density lipoprotein (LDL) cholesterol and blood pressure targets. Combining the 25 trials, each 10-mg/dl decrease in apoB was associated with a 9% decrease in coronary heart disease, no decrease in stroke, and a 6% decrease in major cardiovascular disease risk. Non-high-density lipoprotein (non-HDL) cholesterol decrease modestly outperformed apoB decrease for prediction of coronary heart disease (Bayes factor [BF] 1.45) and cardiovascular disease (BF 2.07) risk decrease; apoB decrease added to non-HDL cholesterol plus LDL cholesterol decrease slightly improved cardiovascular disease risk prediction (1.13) but did not improve coronary heart disease risk prediction (BF 1.03) and worsened stroke risk prediction (BF 0.83). In the 12 statin trials, apoB and non-HDL cholesterol decreases similarly predicted cardiovascular disease risk; apoB improved coronary heart disease prediction when added to non-HDL cholesterol/LDL cholesterol decrease (BF 3.33) but did not improve stroke risk prediction when added to non-HDL cholesterol/LDL cholesterol decrease (BF 1.06). In conclusion, across all drug classes, apoB decreases did not consistently improve risk prediction over LDL cholesterol and non-HDL cholesterol decreases. For statins, apoB decreases added information to LDL cholesterol and non-HDL cholesterol decreases for predicting coronary heart disease but not stroke or overall cardiovascular disease risk decrease.

Section snippets

Methods

Articles were identified by a literature search of the MEDLINE database (1966 to December 1, 2010), English-language journals, a manual search of the authors' reference files, and reference lists of original articles, reviews, and meta-analyses using methods previously described4 to identify randomized controlled trials. Two abstractors independently extracted information using a standardized protocol and reporting form. Disagreements were resolved by consensus. For inclusion in meta-analyses,

Results

Analysis included 25 trials (n = 131,134). For statin trials, 12 met inclusion criteria (n = 101,957); all used statins as monotherapy and 7 were placebo controlled (Table 1) (LaRosa JC, Personal communication, 2010).6, 7, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 For fibrate trials, 4 met inclusion criteria (n = 12,908) and all used a fibrate as monotherapy compared to placebo: 1 used gemfibrozil (n = 2,531), 2 used fenofibrate (n = 10,213), and 1

Discussion

In clinical trials of different lipid-modifying treatments including surgery, magnitude of apoB decrease was associated with magnitude of decrease in coronary heart disease and total cardiovascular disease events, although there was no association with stroke risk decrease. For all types of treatment combined, each 10-mg/dl decrease in apoB was associated with a 9% decrease in coronary heart disease risk and a 6% decrease in major cardiovascular disease risk. In the statin trials a 10-mg/dl

References (57)

  • P. Amarenco et al.

    High-dose atorvastatin after stroke or transient ischemic attack

    N Engl J Med

    (2006)
  • C. Baigent et al.

    Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials

    Lancet

    (2010)
  • T.C. Smith et al.

    Bayesian approaches to random-effects meta-analysis: a comparative study

    Stat Med

    (1995)
  • D.J. Spiegelhalter et al.

    Methods in health service researchAn introduction to bayesian methods in health technology assessment

    BMJ

    (1999)
  • S. Chib

    Marginal likelihood from the Gibbs output

    J Am Stat Assoc

    (1995)
  • R. Kass et al.

    Bayes factors

    J Am Stat Assoc

    (1995)
  • D. Spiegelhalter et al.

    Bayesian measures of model complexity and fit (with discussion)

    J R Stat Soc B Stat Methodol

    (2002)
  • G. Schwarzer

    Meta-AnalysisR Package Version 0.8–2. 2007

  • Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)

    Lancet

    (1994)
  • J. Shepherd et al.

    Prevention of coronary heart disease with pravastatin in men with hypercholesterolemiaWest of Scotland Coronary Prevention Study Group

    N Engl J Med

    (1995)
  • Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levelsThe Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group

    N Engl J Med

    (1998)
  • J.R. Downs et al.

    Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPSAir Force/Texas Coronary Atherosclerosis Prevention Study

    JAMA

    (1998)
  • MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial

    Lancet

    (2002)
  • T.R. Pedersen et al.

    High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial

    JAMA

    (2005)
  • C.P. Cannon et al.

    Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction 22 InvestigatorsIntensive versus moderate lipid lowering with statins after acute coronary syndromes

    N Engl J Med

    (2004)
  • P.M. Ridker et al.

    Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein

    N Engl J Med

    (2008)
  • J. Armitage et al.

    Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial

    Lancet

    (2010)
  • The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass graftsThe Post Coronary Artery Bypass Graft Trial Investigators

    N Engl J Med

    (1997)
  • Cited by (105)

    • Preventive Cardiology

      2022, Practical Cardiology: Principles and Approaches
    View all citing articles on Scopus

    Dr. Robinson has received research grants from the Institution from Amgen, Thousand Oaks, California, Daiichi-Sankyo, Parsippany, New Jersey, Esperion, Plymouth, Michigan, GlaxoSmithKline, Pittsburgh, Pennsylvania, and Merck & Co., West Point, Pennsylvania. Dr. Jacobson has served as a consultant for Abbott, Abbott Park, Illinois, Amarin, Groton, Connecticut, AstraZeneca, Wilmington, Delaware, GlaxoSmithKline, Merck & Co., and Pfizer, New York, New York.

    View full text