Reduction in Coronary Morbidity and Mortality

Simvastatin, pravastatin, and lovastatin have been shown to slow the progression of coronary atheromatous lesions by 2 years after starting treatment, compared with standard care (Blankenhorn et al., 1993 Multicentre Anti-Atheroma Study [MAAS] investigators, 1994 Waters et al., 1994 Jukema et al, 1995). These studies generally reported fewer new lesions and/or total occlusions in the treated group, but regression is less well established, although it may occur in some patients. All of these stud- 

In the megatrials, the impact of inhibitors of HMG-CoA reductase on CHD appears to begin after approximately 1 year of therapy and to increase steadily thereafter as exemplified by 4S (Scandinavian Simvastatin Survival Study Group 1994). The claim by the WOS investigators (Shepherd et al., 1995) that pravastatin produced an earlier effect than 

Hypercholesterolemia is associated with abnormal vascular reactivity (Vita et al, 1990 Seiler et al., 1993), and there is some evidence that lipid lowering with HMG-CoA reductase inhibitors (Treasure et al., 1995 O Driscoll et al., 1997 Simons et al., 1998) and cholestyramine (Leung et al., 1993) can partially reverse this effect within a few months. Improvement in endothelial-dependent vasodilation has also been observed within 24 hours after LDL apheresis in patients with familial hypercholesterolemia this supports the view that high plasma concentrations of LDL adversely affect endothelial function and impair vasodilation (Tamai et al, 1997). However, the Coronary Artery Reactivity After Treatment with Simvastatin (CARATS) study, a large, well-controlled study, provided no evidence for an effect, despite a mean 40% reduction in LDL cholesterol with simvastatin 40 mg daily (Hodgson et al, 1996 Vita et al, 2000). Furthermore, a link between vascular reactivity and coronary events has yet to be established. 

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