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Reducing cholesterol levels in healthy middle-aged men without coronary heart disease (CHD) (in primary prevention studies) reduces risk in direct proportion to the reduction in LDL cholesterol. Treated adults have statistically significant and clinically important reductions in the rates of myocardial infarctions, new cases of angina, need for coronary artery bypass or other revascularization procedures, peripheral artery disease, and stroke. The West of Scotland Study showed a 31% decrease in myocardial infarctions in middle-aged men treated with pravastatin compared with placebo. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) study showed similar results with lovastatin. As with any primary prevention interventions, large numbers of healthy patients need to be treated to prevent a single event. The numbers of patients needed to treat (NNT) to prevent one nonfatal myocardial infarction or one coronary artery disease death in these two studies were 46 and 50, respectively. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) study of atorvastatin in persons with hypertension and other risk factors but without CHD demonstrated a 36% reduction in CHD events. The Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study showed a 44% reduction in a combined end point of myocardial infarction, stroke, revascularization, hospitalization for unstable angina, or death from cardiovascular causes in both men and women. The NNT for 1 year to prevent one event was 169. The Heart Outcomes Prevention Evaluation (HOPE-3) trial of rosuvastatin showed a 24% reduction in cardiovascular events. The NNT over 5.6 years was 91.

Primary prevention studies have found a less consistent effect on total mortality. The West of Scotland study found a 20% decrease in total mortality, tending toward statistical significance. The AFCAPS/TexCAPS study with lovastatin showed no difference in total mortality. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT) also showed no reduction either in all-cause mortality or in CHD events when pravastatin was compared with usual care. Persons treated with atorvastatin in the ASCOT study had a 13% reduction in mortality, but the result was not statistically significant. The JUPITER trial demonstrated a statistically significant 20% reduction in death from any cause. The NNT for 1 year was 400. The HOPE-3 trial showed a 7% reduction in all-cause mortality, but the result was not statistically significant.

In secondary prevention studies among patients with established CVD, the mortality benefits of cholesterol lowering are clearer. Major trials with statins have shown significant reductions in cardiovascular events, cardiovascular deaths, and all-cause mortality in men and women with coronary artery disease. The NNT to prevent a nonfatal myocardial infarction or a coronary artery disease death in these studies was between 12 and 34. Aggressive cholesterol lowering with these agents causes regression of atherosclerotic plaques in some patients, reduces the progression of atherosclerosis in saphenous vein grafts, and can slow or reverse carotid artery atherosclerosis. Results with other classes of medications, particularly those with little effect on LDL or the LDL receptor, have been ...

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