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suggests that all patients at significant risk for vascular events should receive a statin regardless of their cholesterol levels The PROVE-IT trial showed that vascular events were reduced with more aggressive lipid lowering (atorvastatin 80 mg/d compared to pravastatin 40 mg/d following an acute coronary syndrome), providing more evidence of lower is better for patients with vascular disease The TNT (Treating to New Targets) trial likewise found greater benefit with more aggressive LDL lowering (atorvastatin 80 mg versus 10 mg) in a population of patients with coronary heart disease and LDL cholesterol < 130 mg/dL The IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial provided only modest support for very aggressive lipid lowering, showing a nonstatistically significant reduction in major coronary events with 80 mg/d of atorvastatin compared with 20 mg/d of simvastatin in patients with prior myocardial infarction Although true regression of plaque is uncommon even with intensive lipid therapy (as in the REVERSAL and ASTEROID trials), progression can be prevented at least in the short run in many patients Treatment of abnormally low HDL levels or elevations of lipoprotein(a) and small, dense LDL particles is more difficult, but oral niacin in high dosages (2 3 g/d or more) may be effective A trial in postinfarction patients has demonstrated that an increase in HDL levels with gemfibrozil (600 mg twice daily) in patients with relatively low LDL levels prolongs reinfarction-free survival, although the larger FIELD trial failed to show prevention of nonfatal myocardial infarction or coronary heart disease death with fenofibrate for patients with type 2 diabetes mellitus The value of reducing elevated triglyceride levels is less clear, but since elevated triglycerides are often associated with other lipid abnormalities, treatment of high-risk patients with niacin, gemfibrozil, or fenofibrate for levels above 400 mg/dL is appropriate Antioxidant therapy has been advocated as a preventive measure However, many large, well-controlled studies have failed to demonstrate a benefit with vitamin E therapy In fact, the Heart Protection Study and the Heart Outcomes Prevention Evaluation (HOPE) trial found that vitamin E may even be harmful by increasing the likelihood of heart failure and other trials have suggested that vitamin E may hinder the effectiveness of statin therapy Elevated plasma homocysteine levels are associated with an increased risk of vascular events Although homocysteine levels can be reduced with dietary supplements of folic acid (1 mg/d) in combination with vitamin B6 and vitamin B12, two randomized clinical trials have shown that they are of little or no value in preventing vascular events Antiplatelet therapy is another very effective preventive measure Aspirin (325 mg every other day) in males over the age of 50 years reduces the incidence of myocardial infarction A similar approach (100 mg every other day), however, did not prevent myocardial infarction in women age 45 years or older, although stroke did appear to be reduced Thus, the role of aspirin in primary prevention, including the dose, remains controversial A prudent approach would be to administer 81 325 mg daily to men with multiple coronary risk factors or concomitant diabetes starting at age 45 50 years if no contraindication is.

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