Arsonists and Firefighters

A major pharmaceutical success story of the late 20th century was the introduction of statins into clinical medicine. This class of drugs (the firefighters) has contributed to reduced morbidity and mortality from atherosclerotic cardiovascular disease by lowering total cholesterol levels, particularly low-density lipoprotein (LDL) cholesterol (the arsonists), and also by raising high-density lipoprotein cholesterol levels, albeit less dramatically.1 Triglyceride levels may also be reduced. The success of this approach in older adults has also led to the controversial proposal to begin statin therapy even earlier in younger individuals with elevated lipid levels.2 Other benefits have also been attributed to statins, including the effects on inflammatory and immune responses after myocardial infarction.3 Despite this success story, statins are not a panacea. Some patients experience adverse reactions such as myositis that preclude their taking optimal doses and, in some instances, prevent statin use altogether. Much less commonly, statins can lead to rhabdomyolysis, especially in combination with drugs such as gemfibrozil.4 More recently, the US Food and Drug Administration mandated a change in labeling that warns consumers that statins can lead to poorer control of blood glucose levels in patients with type 2 diabetes mellitus.5 Alternative approaches to the treatment of elevated cholesterol levels, for example, therapy with niacin or drugs that influence cholesterol metabolism such as ezetimibe, have either failed in randomized clinical trials6 or fallen out of favor because of the relatively weak strength of evidence.7Article see p 2403In this issue of Circulation , Chatterjee et al8 describe an additive or alternative experimental approach to statin therapy. Sphingosine is an unsaturated18-carbon alcohol that forms the backbone of sphingolipids, which are essential for normal cell membrane structure and function. Sphingolipid metabolites include ceramide and …