Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: III. Efficacy in modifying lipoproteins and implications for managing patients with moderate hypercholesterolemia

In the multicenter, double-blind EXCEL (Expanded Clinical Evaluation of Lovastatin) study the efficacy of lovastatin in modifying plasma lipids and lipoproteins in 8,245 participants with moderate primary hypercholesterolemia was evaluated. Patients were randomly assigned to 48 weeks of treatment with diet and placebo or diet and lovastatin 20 or 40 mg once a day, or 20 or 40 mg twice a day. At all of these dosages, lovastatin produced substantial dose-dependent reductions in low-density-lipoprotein LDL)-cholesterol levels, averaging 24% (20 mg/day) to 40% (80 mg/day). The magnitude of the effect on this lipoprotein was further reflected by the percentage of patients who achieved National Cholesterol Education Program (NCEP) goals. In the absence of coronary artery disease (CAD) or two other CAD risk factors, the LDL-cholesterol goal of 4.14 mmol/L (160 mg/dl) was attained by 22% of patients in the placebo group and between 81% (20 mg/day) and 96% (80 mg/day) of those treated with lovastatin. For those with CAD or at least two other CAD risk factors, the LDL-cholesterol goal of 3.36 mmol/L (130 mg/dl) was attained by 4% of placebo patients and between 38% (20 mg/day) and 83% (80 mg/day) of those treated with lovastatin. Lovastatin also increased high-density-lipoprotein cholesterol (7-10%) and decreased triglycerides (1019%) in a dose-dependent manner. Thus, when used as an adjunct to a prudent diet, lovastatin produces favorable changes in the entire lipoprotein profile and is a highly effective agent for managing patients with primary hypercholesterolemia.
A specific goal of the National Cholesterol Education Program (NCEP) is to help people achieve a blood level of low-density lipoprotein cholesterol (LDL cholesterol, the ''bad'' cholesterol) lower than 160 milligrams per deciliter in the absence of coronary artery disease (CAD) and lower than 130 milligrams per deciliter if CAD or certain CAD risk factors are present. The effectiveness of lovastatin, a drug approved for treating high LDL cholesterol levels, was evaluated in a multicenter, controlled study of 8,245 patients. The patients had moderate hypercholesterolemia (blood cholesterol levels between 240 and 300 milligrams per deciliter) and LDL cholesterol levels above 160 milligrams per deciliter. They were placed on special diets and were randomly assigned to receive one of four different dosages of lovastatin or a placebo drug for 48 weeks. Most patients without CAD or two CAD risk factors who took lovastatin met the study's LDL cholesterol goal (160 milligrams per deciliter): 81 percent of those on the lower dose of lovastatin, and 96 percent of those on the higher dose, were successful. Only 22 percent of the patients treated with the placebo were able to meet this goal. Patients with CAD or two or more CAD risk factors also benefited from lovastatin: 38 percent of those who received the lower dose met the goal, and 83 percent of those on the higher dose were successful. Only 4 percent of these patients who received the placebo lowered their LDL cholesterol levels to the level of the goal. Levels of high-density lipoprotein cholesterol (the ''good'' cholesterol) and triglycerides (another form in which fats are carried in the blood) were also affected positively by lovastatin. The results indicate that this drug is very effective in reducing the level of fats in the blood when used in combination with an appropriate diet. (Consumer Summary produced by Reliance Medical Information, Inc.)