ABSTRACT
The issue of class efficacy for the HMG Co-A reductase inhibitors, or statins as they are called, is one which is under increasing scrutiny by the FDA. These agents have come of age over the past decade and have proved to be relatively safe, very well tolerated, and highly effective cholesterol-lowering agents (Table 1). Indeed, in recent years, the completion of several large clinical endpoint interventional trials has allowed us to answer a number of questions that have dogged this field for a considerable time about the event-reducing efficacy of cholesterol lowering. Moreover, these drugs, either alone or in combination with older therapies, have revolutionized the treatment of hypercholesterolemia. However, not surprisingly, with these developments new medical, scientific, and regulatory issues have evolved. The 4-S study (Scandinavian Symptomatic Survival Study) was a milestone in this area, demonstrating significant clinical benefits associated with pharmacological cholesterol lowering in hypercholesterolemic populations, not only in terms of coronary and cardiovascular morbidity and mortality, but also in terms of total mortality. The ultimate test of the safety and efficacy of a therapeutic intervention in chronic disease is mortality. In the past year, the similarly favorable results of two other studies have been published. The West of Scotland Coronary Prevention Study was published late last year and the CARE (Cholesterol And Current Events) trial was published earlier this fall. The accumulating body of evidence from these large trials speaks to the safety and efficacy of the
individual statins and are supported by a host of smaller studies with different statins. These studies are primarily designed to assess the effect of cholesterol lowering on atherosclerosis progression and have raised important, although complex and somewhat difficult issues not only in the development of new pharmacological agents in this area, but in the regulation of this competitive field. I will discuss the salient features of these three large studies and compare the results across drugs and across trials to point out similarities to make some general conclusions about the effects of the statins in patients at risk for coronary artery disease. This should lead us into the discussion of class clinical efficacy for the statins.
