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Accelerated atherosclerosis and thrombosis occur in saphenous vein coronary artery bypass grafts in over 60% of patients by 10-12 years after grafting, and lead frequently to deterioration of the excellent early clinical results'. This complication is frequently associated with coronary heart disease risk factors, especially hyperlipidaemia. The Post Coronary Artery Bypass Graft trial (Post CABG) studied whether or not intensive low density lipoprotein cholesterol lowering and low-dose oral anticoagulation could delay this late saphenous vein graft disease''. Numerous trials based on angiographic findings have clearly shown that progression of atherosclerosis in the native coronary arteries can be delayed by lipid lowering''. Similarly, several trials with clinical endpoints have reported significant decrease of total mortality and major coronary events associated with cholesterol lowering therapy'"'. In contrast with these trials, two lowering goals of low density lipoprotein cholesterol were compared in Post CABG to determine instead the most beneficial or optimal lowering strategy. A moderate lowering goal of 3-4 to 3-6mmol.l~' was consistent with the recommendations of the National Cholesterol Education Program (NCEP) Adult PANEL I in the U.S.A.'' and the Therapeutic Guidelines of the European Society of Atherosclerosis'. A much lower low density lipoprotein cholesterol goal of 1-6 to 2-2 mmol. 1 ~ ' was selected to minimize the coronary heart disease risk associated with an elevated low density lipoprotein cholesterol blood concentration which starts from a level as low as 16 mmol. I" and increases in a near-linear fashion without a prescribed 40-80 mg of lovastatin daily (mean, 76 mg) whereas the moderate-treatment group was given 2-5-5 mg (mean, 4 mg). Cholestyramine was also prescribed to 30% of patients in the aggressive group and to 5% of the patients in the moderate group, although 35% discontinued in both groups because of drug intolerance. During this 4—5-year trial (mean, 43 years), the low density lipoprotein cholesterol in the aggressive group decreased by 37^40% from a mean of 4 mmol. 1 ~' to 2-42-5 mmol. r 1 , while it fell by 13-15% to 3-43-5 mmol. 1~' in the moderate-treatment group. Of the 1351 participants, 1192 (88%) had a final angiogram. Quantitative (computer-assisted) interpretation of baseline and follow-up angiograms revealed that 27% of grafts per patient in the aggressive group showed substantial progression compared to 39% in the moderate group (P<0-001), a relative difference of 31%. Substantial progression was defined as a decrease in the graft lumen diameter 3=0-6 mm, including new lesions, worsening lesions and occlusions. Risk reductions of 52% and 37-5% were noted, respectively, for new lesions and occlusions. Although this angiographic study was not powered to evaluate clinical events, it showed a lesser incidence of reoperation or angioplasty in the aggressive group: 6-5% vs 9-2% (P=003), a relative difference of 29%. This trial clearly showed that aggressive low density lipoprotein cholesterol lowering to 2-42-5 mmol. I" was more beneficial in Post CABG patients than a moderate reduction to 3-43-5 mmol. 1~'. This lower low density lipoprotein cholesterol target is consistent with the most recent NCEP Adult PANEL II guidelines for secondary clear threshold, according to most epidemiological prevention surveys'. Post CABG is a multicentre, randomized and double blind trial that included 1351 men and women aged 21-74 years who had at least two patent (one in women) saphenous vein grafts placed 1-11 years previously. The low density lipoprotein cholesterol at the first qualifying visit had to be between 3-4 and 5-2 mmol. 1 ~ ' and between 3-4 and 4-6 mmol. 1 ~ ' in at least one of the blood determinations before enrolment. The aggressive-treatment group was The Cholesterol and Recurrent Events Trial (CARE)'' randomly assigned post-myocardial infarction patients with low density lipoprotein cholesterol baseline levels between 3 and 4-5 mmol. I" (mean, 3-6) to either 40 mg of pravastatin per day or to placebo for 5 years. The trial showed a significant decrease in major coronary events by reducing the low density lipoprotein cholesterol by 32% to a mean level below 2-6 mmol. \~\ as in Post CABG.

Optimizing cholesterol lowering therapy: contribution of the Post Coronary Artery Bypass Graft Trial