Statins: Then and Now

The discovery of statins (3-hydroxy-3-methylglutaryl CoA reductase inhibitors) is a consequence of the highly targeted, arduous search for naturally occurring compounds that inhibit cholesterol biosynthesis. An enormous amount of basic scientific, genetic, and clinical research substantiated the role of lipoprotein-derived cholesterol in atherogenesis. Quantifying the impact of lipid lowering on cardiovascular event rates became an issue of utmost urgency. Although a variety of nonstatin drugs had been tested in clinical trials, they found limited utility in the clinical setting due to lack of mortality reduction or tolerability issues. As multiple prospective randomized statin trials began publishing their results, it became clear that reducing atherogenic lipoprotein burden with these drugs was highly efficacious, safe, and generally well tolerated. Statins have been shown to reduce risk for nonfatal MI, ischemic stroke, need for revascularization, and cardiovascular and all-cause mortality. They have also been shown to stabilize and even regress established atherosclerotic plaque. For the first 2 decades of their use, statin dosing was largely determined by risk-stratified low-density lipoprotein cholesterol (LDL-C) goals. More recently, there has been a transition away from LDL-C goal attainment with a focus more on cardiovascular risk and percent LDL-C reduction. Unfortunately, long-term adherence rates with statin therapy remain low and, even when used, they tend to be underdosed.