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

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