HMG coenzyme A reductase inhibitors: good news and bad news.

Abstract

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, commonly called statins, are one of the success stories of modern medicine. Before their introduction and evaluation, the efficacy of lipid-lowering therapy in the prevention of coronary heart disease was controversial. Meta-analyses of clinical trials of bile acid resins, fibric acid derivatives, and other agents demonstrated a reduction in coronary heart disease incidence but not a corresponding fall in overall mortality. These medications did not lower patients' serum cholesterol levels to as marked a degree, had to be taken more frequently, and were much more likely to produce adverse effects compared with statins. In sharp contrast to the preexisting situation, therapy with statins reduces total mortality in men with hypercholesterolemia when used for both primary and secondary prevention of coronary artery disease. In fact, the impressive efficacy of these medications led Brown and Goldstein, winners of the Nobel Prize in medicine, to predict that their availability would lead to the disappearance of coronary artery disease as a public health problem.1 Although a debate of the population-based versus the individual approach to disease prevention is beyond the bounds of this discussion, fulfillment of such an optimistic prediction would be the case only if treatment were applied uniformly to everyone at risk.2