Rosuvastatin in the Primary Prevention of Cardiovascular Disease Among Patients With Low Levels of Low-Density Lipoprotein Cholesterol and Elevated High-Sensitivity C-Reactive Protein

Abstract

Completed randomized trials of statin therapy demonstrate that 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase inhibitors reduce the risk of myocardial infarction, stroke, and other cardiovascular events among individuals with established coronary disease and overt hyperlipidemia.1–6 In aggregate, use of statin therapy in these trials has been associated with an approximate 30% reduction in cardiovascular event rates. Largely on the basis of these cholesterol reduction trials, current treatment algorithms from the National Cholesterol Education Program (NCEP) Adult Treatment Panel III endorse the use of statins in secondary prevention and encourage increased use of statins in primary prevention among those with hyperlipidemia and diabetes.7 Unfortunately, despite evidence provided by the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS2) and the West of Scotland Coronary Prevention Study (WOSCOPS3), use of statins for the primary prevention of cardiovascular disease has not been widely adopted in a cost-effective manner. From a clinical perspective, there are several reasons for this slow adoption. First, almost half of all cardiovascular events occur among apparently healthy men and women who have normal or even low levels of LDL cholesterol (LDL-C). Thus, better screening methods are needed in primary prevention to detect high-risk individuals for whom the number needed to treat (NNT) is small enough to make prophylactic statin therapy cost effective. Second, there has been controversy within the completed clinical trials suggesting that the benefits of statins may extend beyond LDL-C reduction alone. In both the Heart Protection Study of stable high-risk patients6 and the MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering) study of patients with acute coronary syndromes,8 the risk reduction associated with statin therapy was almost identical among those with low as well those with as high levels of LDL-C. Further, statin therapy reduces the risk of stroke, yet LDL-C is not an …