Cholesterol lowering with statins: how WOSCOPS confounded the skeptics.

The appearance of statins was key to our understanding of the pathologic effects of hypercholesterolemia. Before statins were available, physicians did not know whether cholesterol lowering improved cardiovascular health. Pioneering studies such as the Framingham Study and MR FIT identified high blood cholesterol as a risk factor for cardiovascular disease. However, because total cholesterol (TC) < or =300 mg/dL was common physicians were not convinced that this was abnormal. Cholesterol reduction by cholestyramine, nicotinic acid, and fibrates reduced the risk of coronary artery disease, but these treatments did not improve survival and quality of life. In 1987, the first statin arrived. This class of agents lowered cholesterol effectively with minimal side effects. Guidelines started to recognize the importance of cholesterol reduction. There followed a series of endpoint studies that emphatically demonstrated that statins improved cardiovascular outcomes. The WOSCOPS trial showed in a large cohort of men with TC >250 mg/dL and no prior MI that pravastatin dramatically reduced MI incidence, cardiovascular and total mortality, and revascularizations versus placebo over 5 years. WOSCOPS revealed for the first time that statin was effective for primary prevention. The benefits appeared early and persisted even after treatment ended. Statins also changed our perceptions with surprising ancillary effects.