Numerous pathologic, epidemiologic, genetic, and interventional trials have validated the central tenet of the lipid hypothesis, which proposes a causal relationship between dyslipidemia and atherogenesis and identifies lipid modification as a risk-reducing strategy for CHD (see  Chap. 49). Small trials using dietary or drug therapies have demonstrated the angiographic benefit of managing elevated total cholesterol and LDL cholesterol levels. Early clinical trials using bile acid sequestrants, fibrates, or nicotinic acid have reported modest reductions in coronary risk with modest reductions in LDL-C levels.

The advent of the HMG-CoA reductase inhibitors, or statins, in the mid-1980s made more aggressive reduction of LDL cholesterol levels possible. By the late 1990s, several large-scale, prospective randomized trials with these drugs had reported robust reductions in relative cardiovascular risks compared with placebo. This …