Coronary heart disease (CHD) is responsible for more than 650,000 deaths among US residents annually and is the nation's number 1 cause of death.^[1] It is also a leading cause of morbidity, resulting in approximately 700,000 new cases of myocardial infarction (MI) and 500,000 cases of recurrent MI annually.^[1] The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are integral among CHD preventive therapies, significantly reducing the relative risk of coronary events and both coronary and all-cause mortality (vs placebo) by approximately 23% to 37% in several landmark clinical trials by virtue of their ability to modify lipid levels as well as inflammatory, thrombotic, and other mechanisms of atherosclerosis (Figures 1 and 2).^[2-6]

Figure 1. (click image to zoom) Primary and secondary prevention studies demonstrating risk reduction in coronary heart disease (CHD) with statin therapy. WOSCOPS = West of Scotland Coronary Prevention Study; AFCAPS/TexCAPS = Air Force/Texas Coronary Atherosclerosis Prevention Study; 4S = Scandinavian Simvastatin Survival Study; CARE = Cholesterol and Recurrent Events; LIPID = Long-Term Intervention with Pravastatin in Ischaemic Disease Reprinted with permission from National Lipid Association (http://www.lipid.org/).

Figure 2. (click image to zoom) Benefits of aggressive lipid-lowering therapy demonstrated by relationship between low-density lipoprotein cholesterol and relative risk for coronary heart disease. Reprinted with permission from National Lipid Association (http://www.lipid.org/).

Safety concerns about statins peaked after the voluntary worldwide withdrawal of cerivastatin (Baycol) in August 2001 because of a markedly increased reporting rate of fatal rhabdomyolysis (nearly 80 times higher than the rate for other statins available at that time).^[7-9] Concerns increased after a petition was filed with the US Food and Drug Administration (FDA) concerning potential statin-related adverse effects.^[10]

Partly to address these concerns, the National Lipid Association (NLA) appointed a Statin Safety Task Force to evaluate statin safety, encompassing an assessment of the clinical literature; premarketing pharmaceutical data; spontaneous adverse event reports; meta-analyses of randomized clinical trials and analysis of cohort data; and an analysis of a large healthcare claims database.^[11] In this article, we summarize the conclusions of the NLA Task Force and provide recommendations to health professionals who manage primary and secondary coronary prevention using statins. To contextualize the safety data, we also discuss the benefits of statin treatment vs the risk of adverse effects in terms of the number of clinical events per person-year of statin treatment.