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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    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
    Pages (from-to)485-494
    Number of pages10
    JournalJournal of the American College of Cardiology
    Volume64
    Issue number5
    DOIs
    Publication statusPublished - 5 Aug 2014

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  • Cite this

    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