Statin trials and goals of cholesterol-lowering therapy after AMI

Abstract

Several randomized clinical trials using statins in the prevention of coronary heart disease (CHD) have demonstrated benefit, both in terms of retardation of the progression of signs of coronary atherosclerosis and in reduced morbidity and mortality rates. Three of these trials have examined the long-term effect of statins in patients with previous myocardial infarction. The Scandinavian Simvastatin Survival Study (4S) showed that a mean reduction of low-density-lipoprotein (LDL) cholesterol by 35% reduced coronary mortality 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 Intervention with Pravastatin in Ischemic Disease study, the 25% LDL-cholesterol reduction produced a 24% reduction in coronary disease mortality rates and 22% reduction in death from all causes. All event reductions were highly statistically significant. Other trials using statins in patients without signs of CHD have yielded similar risk reductions. Post hoc analysis of the results of the trials have produced diverging indications as to what is the optimal goal of cholesterol lowering. Analysis of the 4S indicates that aggressive treatment aiming at LDL-cholesterol levels lower than the current recommendations of expert panels in the United States and in Europe may yield additional benefit. This strategy finds some support in epidemiological studies and in a study with angiographic end points. Analysis of two trials using pravastatin contradict this and conclude that there is little or no additional benefit of reducing LDL-cholesterol below 125 mg/dL (3.2 mmol/L). Future studies need to address this question prospectively.