Optimising treatment of hyperlipidaemia: Quantitative evaluation of UK, USA and European guidelines taking account of both LDL cholesterol levels and cardiovascular disease risk

  • Handrean Soran
    Corresponding author. University Department of Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
    Cardiovascular Research Group, Faculty of Biology, Medicine and Health, University of Manchester, UK

    University Department of Medicine, Manchester University NHS Foundation Trust, Manchester, UK
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  • Safwaan Adam
    Cardiovascular Research Group, Faculty of Biology, Medicine and Health, University of Manchester, UK

    University Department of Medicine, Manchester University NHS Foundation Trust, Manchester, UK
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  • Paul N. Durrington
    Corresponding author. Cardiovascular Research Group, School of Biomedicine, Core Technology Facility (3rd Floor), University of Manchester, 46 Grafton Street, Manchester, M13 9NT, UK.
    Cardiovascular Research Group, Faculty of Biology, Medicine and Health, University of Manchester, UK
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      • Using equations based on clinical trials, we assess lipid-lowering guidelines.
      • Guidelines should be based on both LDL-C level and absolute CVD risk.
      • Optimal CVD risk reduction in those with higher LDL-C requires treatment targets.
      • Individuals with raised LDL-C can benefit from therapy at lower CVD risk.
      • Fixed dose statins are better for people at higher risk with lower LDL-C levels.


      Background and aims

      Guidelines for cholesterol-lowering medication either advocate fixed dose statin treatment without low density lipoprotein (LDL) cholesterol targets or treatment aimed at LDL cholesterol goals. The decrease in LDL cholesterol concentration determines the reduction in atherosclerotic cardiovascular disease (CVD) risk.


      As indices of the effectiveness of reductions in LDL cholesterol concentration achieved by the various guidelines, the number of CVD events prevented in 100 people during 10 years of treatment (N100) and the number of people, who must be treated for 10 years to prevent one CVD event (NNT), were calculated taking into account both CVD risk and pretreatment LDL cholesterol concentration. That our method of calculating NNT and N100, could be extended to statin regimens of different intensity or of statin combined with adjunctive cholesterol-lowering medication was demonstrated by meta-analysis.


      Reductions in LDL-cholesterol concentration are determined by the choice and dose of medication and by the pre-treatment LDL-cholesterol concentration. At similar CVD risk, whatever cholesterol-lowering strategy is adopted, people with higher pre-treatment LDL cholesterol benefit more than those with lower levels. Fixed dose statin regimens are less effective than target LDL cholesterol levels of 1.8 or 1.4 mmol/l when pre-treatment LDL-cholesterol levels exceed 4 mmol/l. However, fixed dose statin is more effective in people with lower initial LDL cholesterol. The predicted NNT and N100 were closely related to the observed reduction in CVD risk in our meta-analysis.


      In hypercholesterolaemia, aiming for LDL cholesterol targets with statin dose titration (and when necessary adjunctive medication) is essential to optimise benefit.


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