Cholesterol lowering andmortality: theimportance ofconsidering initial level ofrisk// GeorgeDaveymith,Fujian tong, TrevorA!Ieldon

Objective-To investigate thelevel ofrisk ofdeath fromcoronary heart disease above whichcholesterol lowering treatment produces netbenefits. Design-Meta-analysis ofresults ofrandomised controlled trials ofcholesterol lowering treatments. Methods-Published and unpublished data fromallidentified randomised controlled trials of cholesterol lowering treatments withsixmonthsor morefollow upandwithatleast onedeathwere included inthemeta-analysis. Theanalyses were stratified bytherateofdeathfromcoronary heart disease inthecontrol armsofthetrials. Mainoutcome measures-Death fromallcauses, fromcoronary heart disease, andfromcauses other thancoronary heart disease. Results-In thepooled analysis, netbenefit in termsoftotal mortality fromcholesterol lowering wasseenonlyfortrials including patients atvery highinitial riskofcoronary heartdisease (odds ratio 074;95%confidence interval 0-60to0.92). Ina mediumrisk groupnoneteffect wasseen, andinthe lowrisk groupthere wereadverse treatment effects (1.22; 1-06 to1.42). Inaweighted regression analysis asignificant (p<0.001) trend ofincreasing benefit withincreasing initial risk ofcoronary heart disease wasshown. Raised mortality fromcauses other than coronary heartdisease wasseenintrials ofdrug treatment (1.21; 1-05 to1.39) butnotinthetrials of non-drug treatments (1.02; 0-88 to1.19). Cumulative meta-analysis showedthatthese results seemto havebeenstable asnewtrials appeared. Conclusion-Currently evaluated cholesterol lowering drugs seemtoproduce mortality benefits in only asmall proportion ofpatients atveryhigh risk of deathfromcoronary heartdisease. Population cholestrol screening could wasteresources andeven result innetharminsubstantial groups ofpatients. Overall risk ofcoronary heart disease should bethe mainfocusofclinical guidelines, anda cautious approach totheuseofcholesterol lowering drugs should beadvocated. Futuretrials should aimto clarify thelevel ofrisk abovewhichtreatment isof netbenefit.