Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: A meta-analysis of statin trials

S. Matthijs Boekholdt, G. Kees Hovingh, Samia Mora, Benoit J. Arsenault, Pierre Amarenco, Terje R. Pedersen, John C. Larosa, David D. Waters, David A. Demicco, R. John Simes, Antony C. Keech, David Colquhoun, Graham A. Hitman, D. John Betteridge, Michael B. Clearfield, John R. Downs, Helen M. Colhoun, Antonio M. Gotto, Paul M. Ridker, Scott M GrundyJohn J P Kastelein

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322 Scopus citations

Abstract

Background Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented. Objectives The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk. Methods This meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Results Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB. Conclusions The reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.

Original languageEnglish (US)
Pages (from-to)485-494
Number of pages10
JournalJournal of the American College of Cardiology
Volume64
Issue number5
DOIs
StatePublished - Aug 5 2014

Keywords

  • LDL-cholesterol
  • apolipoprotein B
  • meta-analysis
  • non-HDL-cholesterol

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Boekholdt, S. M., Hovingh, G. K., Mora, S., Arsenault, B. J., Amarenco, P., Pedersen, T. R., Larosa, J. C., Waters, D. D., Demicco, D. A., Simes, R. J., Keech, A. C., Colquhoun, D., Hitman, G. A., Betteridge, D. J., Clearfield, M. B., Downs, J. R., Colhoun, H. M., Gotto, A. M., Ridker, P. M., ... Kastelein, J. J. P. (2014). Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: A meta-analysis of statin trials. Journal of the American College of Cardiology, 64(5), 485-494. https://doi.org/10.1016/j.jacc.2014.02.615