Statins and LDL-cholesterol lowering: an overview

Statins have become a cornerstone of treatment for dyslipidaemia primarily due to their marked lowering of low-density lipoprotein cholesterol (LDL-C). Studies show that statin treatment typically reduces relative risk of cardiovascular disease by 24-37%, regardless of age, sex, prior history of coronary heart disease (CHD), or other co-morbid conditions. There is also a growing body of evidence that statins can be effective in people whose LDL-C is not considered elevated under current guidelines. In both the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) and the Collaborative Atorvastatin Diabetes Study (CARDS), participants randomised to atorvastatin (10 mg/day) experienced at least a one-third reduction in major cardiovascular events, even though at baseline, their LDL-C was within the normal range. Other studies have also provided evidence that more intensive lipid-lowering regimens could provide additional clinical benefits. In the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial, the first active-control clinical trial of CHD progression, an intensive lipid-lowering regimen using atorvastatin (80 mg/day) decreased atherogenic lipoproteins and atheroma volume in patients with established CHD, compared with a moderate regimen using pravastatin (40 mg/day). Furthermore, relative to baseline, there was no measurable atheroma progression in the atorvastatin group. While statin therapy does offer significant clinical benefit, 60-70% of major cardiovascular events are still not prevented, which underscores the need for alternative interventions. Targeting inflammatory mediators of atherosclerosis such as C-reactive protein (CRP), as well as combination therapy to simultaneously raise high-density lipoprotein cholesterol (HDL-C) and lower LDL-C, are among the promising new strategies for primary and secondary prevention of atherosclerotic disease. This article will summarise data concerning use of statins in patients without markedly elevated LDL-C. The issue of the ideal LDL-C target will also be considered before addressing future treatment options for dyslipidaemia.