Statins, LDL Cholesterol Control, Cardiovascular Disease Prevention, and Atherosclerosis Progression: A Clinical Perspective

Despite the longstanding and widespread use of statins, they are used quite inefficiently in everyday clinical practice. This might be because of a lack of robust evidence or the wide variety of different guidelines that are frequently changed. Using data from clinical trials and some simple mathematical modeling, we sought to expand upon the relation between low-density lipoprotein cholesterol (LDL-C) control and cardiovascular risk to offer a firm basis for independent decision making in everyday clinical practice. Analysis of the dose–response curves of different statins indicated that doubling the dose will provide a < 5% extra LDL-C gradient and that the relationship among different statin dose equipotencies is fourfold in the lower range and threefold in the higher range. Thus, the use of potent statins at very low doses might overcome patient statin reluctance. Moreover, whereas statins lower LDL-C percentwise, the prevention of atherosclerosis-related cardiovascular events (ARCVEs) depends on the absolute LDL-C gradient produced and the level of risk. Consequently, and counterintuitively, the lower the baseline LDL-C and/or ARCVE risk, the higher the statin therapy strength required, and approach that is also cost effective. We discuss the issue of threshold versus gradient in terms of clinical trials on plaque regression and speculate on the relationship between LDL-C and atherosclerosis.