Effects of baseline level of triglycerides on changes in lipid levels from combined fluvastatin + fibrate (bezafibrate, fenofibrate, or gemfibrozil).

This analysis was conducted to evaluate the effect of baseline triglyceride levels on lipid and lipoprotein changes after treatment with the combination of fluvastatin and fibrates. The analysis involved pooling data from 10 studies that included 1,018 patients with either mixed hyperlipidemia or primary hypercholesterolemia. Patients received a combination of fluvastatin and a fibrate (bezafibrate, fenofibrate, or gemfibrozil) from 16 to 108 weeks. The combination of fluvastatin and a fibrate improved lipid profiles, with reductions in triglycerides, low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol that were dependent on baseline triglyceride levels. The greatest triglyceride reductions were observed in patients with high baseline triglyceride levels (> or =400 mg/dl) (41%, p <0.0001). The greatest LDL cholesterol and non-HDL cholesterol reductions occurred in patients with normal baseline triglyceride levels (<150 mg/dl) (35% and 33%, respectively; p <0.0001). The combined fluvastatin-fibrate therapy was well tolerated. Two patients (0.2%) (1 patient on fluvastatin 80 mg + gemfibrozil 1,200 mg and 1 patient on fluvastatin 20 mg + fenofibrate 200 mg) had creatine kinase levels > or =10 times the upper limit of normal, 11 patients (1.1%) had an elevation in alanine transaminase >3 times the upper limit of normal, and 7 patients (0.7%) had elevations in aspartate transaminase >3 times the upper limit of normal. Combined fluvastatin-fibrate therapy takes advantage of the complementary effects of the 2 agents, with the extent of triglyceride, LDL cholesterol, and non-HDL cholesterol lowering dependent on baseline triglyceride levels. The combination of fluvastatin and fibrates was well tolerated with no major safety concerns.

The impact of the National Cholesterol Education Program Adult Treatment Panel III guidelines on drug development.

In the newest guidelines of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III, more intensive low-density lipoprotein cholesterol-lowering therapy, together with more attention to other lipid and lipoprotein parameters, are recommended for a larger group of dyslipidemic patients than was covered under ATP I and ATP II. A discussion to evaluate how future drug development might be affected by these new guidelines took place at the 14th International Symposium on Drugs Affecting Lipid Metabolism (DALM) conference, held in New York in September 2001. These discussions involved how to develop new lipid-lowering drugs in an era in which so much compelling evidence demonstrates the benefits of statins. Also covered were issues related to the development of drugs with triglyceride indications and whether the proportion of patients achieving NCEP guidelines should be included in the label of lipid-lowering drugs. Additional topics discussed included: (1) the possibility of incorporating a non-high-density lipoprotein cholesterol (HDL-C) indication for lipid-lowering drugs, (2) the possibility of obtaining indications for lipid-lowering drugs specifically in patients with diabetes, (3) the place of combination lipid-lowering drug therapy in drug development, and (4) whether drugs could be approved to increase levels of HDL-C in patients with isolated low HDL-C.