Statin trials and goals of cholesterol-lowering therapy after AMI

Several randomized clinical trials using statins in the prevention of coron ary heart disease (CHD) have demonstrated benefit, both in terms of retarda tion of the progression of signs of coronary atherosclerosis and in reduced morbidity and mortality rates. Three of these trials have examined the lon g-term effect of statins in patients with previous myocardial infarction. T he Scandinavian Simvastatin Survival Study (4S) showed that a mean reductio n of low-density-lipoprotein (LDL) cholesterol by 35% reduced coronary mort ality rates by 42% and total mortality rates by 30%. In the Cholesterol and Recurrent Events trial, a 28% reduction in LDL-cholesterol was associated with a reduction in major coronary events of 24%. In the Long Term Interven tion with Pravastatin in Ischemic Disease study, the 25% LDL-cholesterol re duction produced a 24% reduction in coronary disease mortality rates and 22 % reduction in death from all causes. All event reductions were highly stat istically significant. Other trials using statins in patients without signs of CHD have yielded similar risk reductions. Post hoc analysis of the resu lts of the trials have produced diverging indications as to what is the opt imal goal of cholesterol lowering. Analysis of the 4S indicates that aggres sive treatment aiming at LDL-cholesterol levels lower than the current reco mmendations of expert panels in the United States and in Europe may yield a dditional benefit. This strategy finds some support in epidemiological stud ies and in a study with angiographic end points. Analysis of two trials usi ng pravastatin contradict this and conclude that there is little or no addi tional benefit of reducing LDL-cholesterol below 125 mg/dL (3.2 mmol/L). Fu ture studies need to address this question prospectively.