Cholesterol, High Cholesterol

Brown, BG et al evaluated patients randomly assigned to 1 of 4 regimens with previous heart attacks, previous coronary intervention, and history of angina: simvastatin plus niacin, antioxidant vitamins, simvastatin–niacin plus antioxidants, or placebo. All patients also had at least one stenosis over 50% or 3 stenoses of at least 30%. If LDL-C was 110 mg/dL or lower at the start of the study, patients received 10 mg simvastatin and 20 mg if LDL-C was greater than 110 mg/dL. Patients receiving simvastatin (Zocor) had their dose titrated to a goal LDL-C level of 40 to 90 mg/dL. In the first year, if any patient had a LDL-C below 90 mg/dL, the simvastatin dose was increased by 10 mg/d and was decreased by 10 mg/d if LDL-C was below 40 mg/dL at any time. Placebo patients were given 10 mg simvastatin if LDL-C was greater than 140 mg/dL, with a target of 130 mg/dL or less. In patients receiving niacin, the dose was titrated over 1 month to at least 1000 mg twice per day (mean final dose 2.4 grams/day). Niacin 50 mg twice per day was used as the placebo to produce a flushing effect and thus keep patients blinded. Antioxidants were given twice daily, with total dosage of 800 IU vitamin E, 1000 mg vitamin C, 25 mg natural beta-carotene, and 100 μg selenium. Results revealed that major heart events were cut by 60-90% in patients taking simvastatin plus niacin. They also had significantly fewer cardiovascular events than those given placebo (21% vs 2.6%). However, addition of antioxidants actually reduced this effect: when antioxidant therapy was added to lipid lowering, the rate of clinical events increased to that observed with placebo. There was also no difference between patients receiving antioxidants alone and those receiving placebo. Patients receiving simvastatin plus niacin had small increases in aspartate aminotransferase (higher levels of this enzyme may signal heart or liver disease), creatine kinase (marker of heart, muscle damage), uric acid, homocysteine (high levels increase risk of heart attacks, strokes, blood clots), and insulin. (67)