Beyond lipid lowering: What have we learned about the benefits of statins from the acute coronary syndromes trials?

The long-term benefits for prevention of primary and secondary cardiovascular events achieved by lowering serum cholesterol levels with statins are undisputed. However, results of early clinical trials and preclinical studies suggested the possibility that benefits of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may not be entirely due to their effects on low-density lipoprotein (LDL) cholesterol. Since then, large-scale clinical trials of statin treatment for acute coronary syndromes (ACS) have demonstrated early benefits that are associated with aggressive initiation of statin therapy. Support for pleiotropic effects of statins in these trials has been provided not only by these acute effects but also by apparent differences in efficacy between various statin regimens that seem unrelated to their effects on serum cholesterol levels. Analyses of biomarkers of inflammation, oxidation, and thrombosis in samples from patients in these studies have also suggested possible mechanisms underlying the benefits of statins in ACS. This article reviews some of the key statin trials in ACS and assesses the evidence for benefits of these drugs independent of their effects on LDL cholesterol.