Coronary angiographic trials have demonstrated that the lowering of
cholesterol slows the progression of
atherosclerosis, enhances atherosclerotic regression, limits the formation of new lesions, and reduces the incidence of coronary events. Atherosclerotic progression has been shown to be associated with an increased risk of
cardiac death,
cardiac death plus nonfatal
myocardial infarction (MI), and all coronary events. Most of the atherosclerotic regression trials were too small and of too short duration to demonstrate a significant difference in hard coronary events between patients receiving
cholesterol-lowering intervention and controls. However, when data from these studies were pooled, total mortality was found to be reduced by 26% and the rate of nonfatal MI by 39% in actively treated patients. The first events trial to demonstrate clearly a reduction in overall mortality was the Scandinavian
Simvastatin Survival Study (4S), in which lowering of serum
cholesterol in patients with
coronary artery disease (CAD) and
hypercholesterolemia also reduced coronary mortality, fatal and nonfatal MI,
sudden cardiac death, and the need for revascularization. Reductions in major coronary events were seen consistently in all subgroups of patients studied and regardless of concomitant
therapy with
aspirin, beta blockers, or
calcium antagonists. Further evidence of the benefit of
cholesterol-lowering
therapy was provided by the West of Scotland Coronary Prevention Study (WOSCOPS), which evaluated men with
hypercholesterolemia but no history of CAD. Those receiving active treatment had less overall mortality, lower risk of definite nonfatal MI or death from definite or suspected CAD, and less need for revascularization. The
Cholesterol and Recurrent Events (CARE) Study recently showed that
lipid-lowering
therapy is also beneficial in CAD patients with less severe
dyslipidemia.