Clinical perspectives on primary and secondary prevention of coronary atherosclerosis

Several clinical trials have provided compelling evidence in support of the benefits of lipid-lowering therapy for primary and secondary prevention of atherosclerosis. The results of primary prevention trials have demonstrated that coronary morbidity can be reduced and survival improved with effective lipid-lowering regimens. There has been concern, however, regarding harmful effects (e.g., increased rate of suicide and increased risk of gastrointestinal cancer) of cholesterol-lowering therapies in primary prevention trials. These concerns are not well supported by strong evidence, and there has been lack of a dose-response relationship. It is generally believed that for 1% reduction in serum cholesterol, there is a 2% reduction in the risk of coronary events. The results of numerous secondary prevention trials have clearly demonstrated the benefit of lipid-lowering therapies in reducing the risk of future cardiac events and cardiac mortality in patients with preexistent coronary artery disease. Several studies have shown that treatment regimens effective in reducing LDL cholesterol levels lead to regression of atherosclerotic plaques as well as retard the progression of the disease process. Interestingly, some of these studies have also shown that when measured angiographically, the luminal diameter at the site of stenotic lesions might improve only by an average of 2% to 3%; however, this small degree of improvement is associated with a remarkable reduction by 35% to 25% in the risk of future coronary events. These findings further corroborate the hypothesis about the importance of a lipid-rich cap of the vulnerable plaques and suggest that the reduction in lipid levels is associated with the efflux of lipids from the plaque, thus converting it from a vulnerable to a stable state. The most recent data from the 4S trial have unequivocally demonstrated the benefits of treatment with HMG coenzyme-A reductase inhibitors in reducing the risk of future coronary events and improving the overall survival in patients with established CHD. Although there is still ongoing controversy regarding the precise course of action for primary prevention of CHD, the results of a large number of studies provide overwhelming evidence in support of aggressive lipid-lowering therapy for secondary prevention of CHD. Based on the findings of these studies, it seems prudent that clinicians become actively involved in the evaluation and management of lipid abnormalities and other risk factors in patients with CHD.