Rosuvastatin: a highly potent statin for the prevention and management of coronary artery disease

Figure 1. Updates to NCEP/ATP-III guidelines for cholesterol management. Based on data from the Heart Protection Study (HPS) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) trial, major updates were proposed to the 2001 guidelines. An 'optional'target of LCL-C less than 70 mg/dl was recommended for patients at 'very high risk'of coronary events, which includes established CHD plus either non-coronary atherosclerosis, diabetes mellitus or a greater than 20% calculated Framingham 10-year CHD risk. Furthermore, individuals with two or more risk factors and a calculated Framingham 10-year CHD risk of 10-20% have the 'optional'target LDL-C of <100 mg/dl CAD: Coronary artery disease; CHD: Coronary heart disease; CVD: Cardiovascular disease; HDL-C: High-density liporpotein cholesterol; TG: Triglyceride. Adapted from [15].
(Figure omitted. See article PDF.)

Figure 2. Rosuvastatin. bis [(E)-7- [4-(4-fluorophenyl)-6-isopropyl-2- [methyl (methylsulfonyl)amino] pyrimidin-5-yl] (3R,5S) -3,5- dihydroxyhept-6-enoic acid] calcium. The empirical formula is [(C₂₂ H₂₇ FN₃ )₆ S₂ ]Ca. A fluorinated phenyl group and a polar methane sulphonamide group (yellow circles) afford enhanced potency against HMG-CoA reductase, a rate-limiting step in cholesterol biosynthesis.
(Figure omitted. See article PDF.)

Coronary heart disease (CHD) accounts for 1.2 million myocardial infarctions (MIs) and 650,000 deaths annually in the USA, making it the leading cause of death in both American men and women. CHD is responsible for nearly 30% of mortality worldwide [1]. The association between cholesterol and atherosclerosis dates back to the early 1900s when the German chemist Adolph Windaus determined that atheromatous plaque from human aortas contained 20-fold higher concentrations of cholesterol than normal aortas. Soon afterwards, the Russian pathologist Nikolai Anitschov provided the first animal model of atherosclerosis by feeding rabbits a high-cholesterol diet [2,3]. In 1955, a biophysicist named John Gofman used ultracentrifugation to separate plasma lipoproteins by density, and correlated risk of MI with elevated low-density lipoprotein cholesterol (LDL-C) levels. Henceforth, the 'lipid hypothesis'proposed that elevated LDL-C, elevated triacylglycerols (TGs), and low levels of high-density lipoprotein cholesterol (HDL-C) were causally associated with an increased risk of CHD [4]. Two decades later, in 1976, the Japanese scientist Akira Endo identified a fungal metabolite that blocks cholesterol synthesis by inhibiting the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, resulting in the first 'statin'agent, mevastatin [5]. Since their introduction into the marketplace in 1986,...