The aggressive low density lipoprotein lowering controversy
James S. Forrester, MD, FACCa,b,
C. Noel Bairey-Merz, MD, FACCa,b and
Sanjay Kaul, MDa
a Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
b University of California at Los Angeles School of Medicine, Los Angeles, California, USA
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Figure 1 The relation between risk of CHD events and LDL levels achieved with statin therapy in secondary and primary prevention trials. In the secondary prevention trials (A), patients are at higher antecedent risk of a coronary event, and there appears to be a curvilinear relation, similar to the epidemiologic relation. In the primary prevention trials (B), with lower risk patients, the relation is much less steep. 4S = Scandinavian Simvastatin Survival Study; CARE = Cholesterol And Recurrent Events trial; LIPID = Long-term Intervention with Pravastatin in Ischemic Disease Study; WOSCOPS = West Of Scotland COronary Prevention Study; AFCAPS/TexCAPS = Air Force Coronary/Texas Atherosclerosis Prevention Study. P = placebo; T = treatment.
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Figure 2 Relation of percent reduction in CHD events and pretreatment LDL cholesterol, percent LDL reduction and post-treatment LDL in major clinical trials of statin therapy. The best correlation is with pretreatment LDL. The regression curve is derived from the following regression equations: pretreatment LDL (y = –1.73 + 0.18 pretreatment LDL, R2 = 0.86, p = 0.015); percent LDL reduction (y = 4.69 + 0.82 percent LDL reduction, R2 = 0.36, p = 0.17); post-treatment LDL (y = 3.77 + 0.20 post-treatment LDL, R2 = 0.27, p = 0.21). See Figure 1 legend for study acronyms.
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Figure 3 Interpopulation differences in CAD mortality according to quartiles of total serum cholesterol levels (27). Between countries, there are major differences in the cardiac event rate at approximately the same level of serum cholesterol.
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Figure 4 Predicted CHD deaths at different cholesterol levels as predicted from epidemiologic studies (Framingham risk model) versus observed therapy (WOSCOPS [30]). One explanation for the difference in cardiac events is that statins may also reduce cardiac events by non-LDL–lowering effects. There are a number of variables, however, that may confound such a comparison. For example, there are differences in age, gender, distribution of ethnic groups and prevalence of risk factors in the two populations. As seen in Figure 3, the impact of these and other variables may be substantial.
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