Low-density lipoprotein-lowering strategies: target versus maximalist versus population percentile

Maximalist low-density lipoprotein (LDL)-lowering strategies such as lowering LDL as much as possible or, alternatively, using the most potent LDL-lowering regimens have become increasingly popular. Almost all attention has focused on the potential advantages of these approaches with little focus on their potential disadvantages. Moreover, it is increasingly assumed that the lower and lower is better and better approach is supported by unassailable evidence.

This article will examine how strongly the findings of the statin clinical trials actually support the maximalist strategy. We will also introduce a new approach, the population percentile strategy, which is based on the fact that the amount of cholesterol in LDL can differ substantially. When cholesterol-depleted LDL particles are present, LDL cholesterol (LDL-C) underestimates apolipoprotein B (apoB) and LDL particle number. Statins lower LDL-C and nonhigh-density lipoprotein cholesterol (non-HDL-C) more than they lower apoB and LDL particle number. This means that, even if LDL-C, non-HDL-C and apoB are equal markers of on-treatment risk, apoB is a better marker of the adequacy of LDL-lowering therapy.

Our analysis indicates that the LDL-lowering regimen should be tailored to the individual using a population percentile strategy to ensure the greatest number of patients receive the greatest overall benefit. With this approach, apoB is the best marker of the adequacy of LDL-lowering therapy.