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A combination of diet therapy and lovastatin may not be more effective than treatment with lovastatin alone in patients with hypercholesterolemia, or increased blood levels of cholesterol. Diet therapy for hypercholesterolemia involves a diet low in saturated fat and cholesterol. Ninety-seven patients with moderate hypercholesterolemia participated in four nine-week periods of treatment with a low-fat diet and lovastatin, a high-fat diet and lovastatin, a low-fat diet and a placebo (an inactive substance) and a high-fat diet and a placebo. The low-fat diet alone only reduced low-density lipoprotein (LDL) cholesterol by 5%, but lovastatin alone reduced LDL cholesterol 27%. Together, they reduced LDL cholesterol by 32%. However, the low-fat diet blocked the drug-induced increase in blood levels of high-density lipoprotein (HDL) cholesterol. This may interfere with the positive effects of drug therapy.

This study compared the relative efficacy of a once-daily niacin extended-release (ER)/lovastatin fixed-dose combination with standard doses of atorvastatin or simvastatin, with a special emphasis on relative starting doses. Subjects (n = 315) with elevated low-density lipoprotein (LDL) cholesterol and decreased high-density lipoprotein (HDL) cholesterol blood levels (defined as LDL cholesterol blood levels ≥160 mg/dl without coronary artery disease, or ≥130 mg/dl if coronary artery disease was present, and HDL cholesterol <45 mg/dl in men and <50 mg/dl in women) were randomized to atorvastatin, simvastatin, or niacin ER/lovastatin for 16 weeks. The primary efficacy variables were the mean percent change in LDL cholesterol and HDL cholesterol levels from baseline. After 8 weeks, the starting dose niacin ER/lovastatin 1,000/40 mg and the 10-mg starting dose atorvastatin both lowered mean LDL cholesterol by 38%. After 12 weeks, niacin ER/lovastatin 1,000/40 mg lowered LDL cholesterol by 42% versus 34% with the 20-mg starting dose of simvastatin (p <0.001). Niacin ER/lovastatin increased HDL cholesterol significantly more than atorvastatin or simvastatin at all compared doses (p <0.001). Niacin ER/lovastatin also provided significant improvements in triglycerides, lipoprotein(a), apolipoprotein A-1, apolipoprotein B, and HDL subfractions. A total of 6% of study subjects receiving niacin ER/lovastatin withdrew because of flushing. No significant differences were seen among study groups in discontinuance due to elevated liver enzymes. No drug-induced myopathy was observed. Niacin ER/lovastatin was comparable to atorvastatin 10 mg and more effective than simvastatin 20 mg in reducing LDL cholesterol, was more effective in increasing HDL cholesterol than either atorvastatin or simvastatin, and provided greater global improvements in non-HDL cholesterol, triglycerides, and lipoprotein(a). [Copyright &y& Elsevier]

The efficacy and safety of ezetimibe, a new cholesterol absorption inhibitor, was evaluated in this randomized, double-blind, placebo-controlled trial of 892 patients with primary hypercholesterolemia. After ≥2 weeks on the National Cholesterol Education Program (NCEP) Step I or a stricter diet and a 4- to 8-week single-blind placebo lead-in, patients with low-density lipoprotein (LDL) cholesterol 130 to 250 mg/dl and triglycerides ≤350 mg/dl were randomized 3:1 to receive ezetimibe 10 mg or placebo orally each morning for 12 weeks. The primary efficacy end point was the percent reduction in direct plasma LDL cholesterol from baseline to end point. A total of 434 men and 458 women (ages 18 to 85 years) received randomized treatment (666 ezetimibe 10 mg, 226 placebo). Demographics and baseline characteristics were similar between treatment groups. Ezetimibe significantly reduced direct LDL cholesterol by a mean of 16.9%, compared with an increase of 0.4% with placebo (p <0.01). Subgroup analysis indicated that response to ezetimibe was generally consistent across all subgroups, regardless of risk-factor status, gender, age, race, or baseline lipid profile. Ezetimibe effects on LDL cholesterol occurred early (2 weeks) and persisted throughout the 12-week treatment period. Compared with placebo, ezetimibe 10 mg also significantly improved calculated LDL cholesterol, apolipoprotein B, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and HDL3 cholesterol (p <0.01). Ezetimibe was well tolerated. There were no differences in laboratory or clinical safety parameters, or gastrointestinal, liver, or muscle side effects from that of placebo. Ezetimibe 10 mg/day is well tolerated, reduces LDL cholesterol approximately 17%, and improves other key lipid parameters. [Copyright &y& Elsevier]

Compares the bioavailability, safety and efficacy of fluvastatin (synthetic 3-hydroxy-3-methylglutaryl-coenzyme A) when administered with the evening meal compared with bedtime. Demographic characteristics and medical history of subjects; Changes in lipid parameters; Changes from baseline in total and low-density lipoprotein (LDL) cholesterol levels.

BACKGROUND: Combination lipid-lowering therapy may be desirable in patients with elevated low-density lipoprotein cholesterol, high triglycerides, and low high-density lipoprotein cholesterol. This study was conducted to determine the lipid-lowering efficacy of the combination of low-dose simvastatin and niacin in patients with combined hyperlipidemia and low high-density lipoprotein cholesterol. METHODS AND RESULTS: In this multicenter, prospective, randomized trial, 180 patients with hypercholesterolemia and hypertriglyceridemia and/or low high-density lipoprotein cholesterol were randomized to combination simvastatin (10 mg/day) and niacin (0.75 g/day) or to either drug alone for 9 weeks. The dose of niacin was doubled (from 0.75 g/day to 1.5 g/day) in both the combination and niacin arms for the remaining 8 weeks. The combination of simvastatin, 10 mg/day, and niacin, 1.5 g/day, reduced total, low-density lipoprotein, and very low-density lipoprotein cholesterol and triglycerides by 24%, 29%, 45%, and 31%, respectively, while increasing high-density lipoprotein cholesterol by 31%. The addition of niacin to simvastatin did not enhance the low-density lipoprotein cholesterol by 31%. The addition of niacin to simvastatin did not enhance the low-density lipoprotein cholesterol-lowering effect of simvastatin; however, the combination was more effective than either monotherapy at raising high-density lipoprotein cholesterol and lowering very low-density lipoprotein cholesterol (P <.05). More patients discontinued treatment because of an adverse event in the niacin (P <.03) and combination groups (P =.06) than the simvastatin group. CONCLUSIONS: Treatment of patients with combined hyperlipidemia and/or low high-density lipoprotein with combination low-dose simvastatin and niacin resulted in large reductions in total, low-density lipoprotein, and very low-density lipoprotein cholesterol and increases in HDL cholesterol. Although the combination was well tolerated in the current trial, its safety needs to be evaluated in larger trials of longer duration. [ABSTRACT FROM AUTHOR]