Prevention and regression of atherosclerosis: effects of HMG-CoA reductase inhibitors

OBJECTIVE: To review the current literature on the effects of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors in secondary prevention and regression of atherosclerosis. DATA SOURCES: A MEDLINE and journal search of recent studies evaluating the effects of lipid lowering with HMG-CoA reductase inhibitors on serum cholesterol as well as progression and regression of atherosclerotic coronary or carotid disease in patients with established atherosclerotic disease was conducted. Articles addressing the pathophysiology of atherosclerotic disease were identified by using the same sources. STUDY SELECTION: All available studies evaluating the use of HMG-CoA reductase inhibitors in the progression and regression of coronary and carotid atherosclerosis were reviewed. DATA SYNTHESIS: Lowering of total serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, as well as increasing high-density lipoprotein cholesterol can be achieved with HMG-CoA reductase inhibitors. Aggressive lipid lowering has been demonstrated to alter progression of established atherosclerotic disease and, in some patients, actually induce regression of the atheroma. An unexpected finding of several trials was the early and significant reduction in clinical cardiac events. Other mechanisms by which clinical event reduction may be explained include plaque stabilization and restoration of endothelium vasodilation. CONCLUSIONS: Aggressive lipid-lowering therapy using HMG-CoA reductase inhibitors appears to alter the natural progression and promote regression of atherosclerosis in selected patients with established coronary or carotid atherosclerosis. However, it is unlikely that regression of atherosclerosis alone is responsible for the marked reduction in clinical cardiac events seen in these trials.

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