Treatment goals for low-density lipoprotein cholesterol in the secondary prevention of coronary heart disease: absolute levels or extent of lowering?

The results of the Scandinavian Simvastatin Survival Study (4S) and the Cholesterol and Recurrent Events (CARE) study make abundantly clear the benefits of lowering low-density lipoprotein (LDL) cholesterol in patients with a history of coronary artery disease. Current guidelines in the United States and Germany recommend a treatment goal for LDL cholesterol of 100 mg/dl. However, the evidence for setting such a goal is not consistent among trials. It has even been argued that setting an absolute LDL goal may be unhelpful, per se, because the higher the patient's pretreatment LDL cholesterol, the more difficult achieving this goal becomes. It has also been recognized that measures to lower LDL cholesterol, and medications in particular, produce a relative rather than an absolute degree of reduction in circulating levels. For example, most statins produce a similar proportional decrease in LDL cholesterol irrespective of baseline LDL. Thus, if the baseline LDL is 180 mg/dl, the decrease in LDL with a particular statin dose may be 60 to 120 mg/dl, whereas if the baseline LDL is 120 mg/dl, the expected decrease in LDL with the same statin dose would be only 40 to 80 mg/dl (i.e., a 30% reduction in each case). These points have led some investigators to suggest that it may be more practicable to recommend the amount by which LDL should be lowered rather than by specifying an absolute level of LDL cholesterol which should be achieved. This report summarizes the proceedings of an international symposium held on this topic on October 4, 1996, in Berlin by the International Task Force for Prevention of Coronary Heart Disease and the Institute of Arteriosclerosis Research at the University of Münster.