Influence of lovastatin plus gemfibrozil on plasma lipids and lipoproteins in patients with heterozygous familial hypercholesterolemia

Abstract

We investigated the hypocholesterolemic effects of lovastatin alone and in combination with gemfibrozil on plasma lipids and lipoproteins in 12 adult patients with well-characterized heterofzygous familial hypercholesterolemia. Plasma concentrations of low density lipoprotein (LDL) cholesterol decreased from 321 ± 14 mg/dl on diet only to 207 ± 8 mg/dl (-35.5%) on single-drug therapy with lovastatin at a dose of 40 mg twice daily, whereas triglyceride concentrations fell by 27.6% (from 145 ± 20 to 105 ± 20 mg/dl). Subsequent addition of gemfibrozil at a dose of 600 mg twice daily resulted in a nonsignificant further reduction in LDL cholesterol to 194 ± 7 mg/dl (-39.6% change from baseline), whereas triglycerides decreased to 80 mg/dl (-44.8%, p < 0.05 vs. single-drug therapy with lovastatin). Plasma concentrations of high density lipoprotein (HDL) increased slightly during lovastatin and combined drug therapy (from 45 ± 4 mg/dl at baseline to 46 ± mg/dl on lovastatin to 48 ± 4 mg/dl on lovastatin plus gemfibrozil). The response to combination drug therapy in individual patients was heterogeneous and clinically significant decreases in LDL cholesterol concentrations were noted in two of the 12 patients, whereas in three patients LDL cholesterol concentrations increased on the combined drug regimen. One patient developed an asymptomatic increase in creatine kinase on monotherapy with lovastatin and a more pronounced and symptomatic increase during combination drug therapy with lovastatin plus gemfibrozil. We conclude that the combination of lovastatin plus gemfibrozil does not provide significant further LDL lowering as compared with monotherapy with lovastatin alone in patients with heterozygous familial hypercholesterolemia and that this combined drug regimen may be associated with an increased risk of myopathy.