Therapeutic efficacy of the lipid-lowering armamentarium: the clinical benefits of aggressive lipid-lowering therapy.

Hypercholesterolemia, particularly an elevated level of low-density lipoprotein (LDL) cholesterol, is an unarguably established risk factor for coronary artery disease (CAD). It is equally well established that lowering LDL cholesterol levels will decrease CAD-related morbidity and mortality in patients with established CAD. Although lipid-lowering therapy is known to retard the progression of atherosclerosis in patients with native coronary arteries, its effect in patients with coronary bypass grafts, which are particularly vulnerable to occlusion, is less well understood. Moreover, whereas several major clinical trials have documented the benefits of lowering LDL cholesterol in a variety of patient subpopulations, there has been far less clarity surrounding the question of whether aggressive lowering of LDL cholesterol is of greater benefit than moderate lowering of LDL cholesterol. The Post Coronary Artery Bypass Graft (Post-CABG) trial, a multicenter, randomized, double-blind clinical trial comprising 1,351 patients with elevated levels of LDL cholesterol and a history of bypass surgery was designed to determine whether aggressive lowering of LDL cholesterol levels with therapy based on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") is more effective than moderate lowering in delaying the progression of atherosclerosis in bypass grafts. Quantitative computer-assisted angiography was conducted at baseline and again at an average of 4.3 years. The primary angiographic outcome was the mean percentage per patient of grafts with a decrease of > or = 0.6 mm in lumen diameter. Patients who received aggressive therapy were significantly more likely than their moderate-treatment counterparts to achieve and maintain LDL cholesterol levels within the National Cholesterol Education Program's (NCEP's) recommended target of < or = 100 mg/dL (< or = 2.59 mmol/L). Moreover, the mean percentage of grafts with progression of atherosclerosis was 27% for aggressively treated patients, compared with 39% for those who were randomized to the moderate-treatment group (p < 0.001). This study demonstrates that aggressive lipid lowering is practical and worthwhile in at-risk patients. Aggressive treatment is far more effective than moderate treatment in lowering LDL cholesterol levels to the NCEP target level of < or = 100 mg/dL (< or = 2.59 mmol/L), and this intervention decreases the progression of atherosclerosis.