The most appropriate
therapy for combined
hyperlipidemia remains to be determined. We compared the
lipid-regulating effects of
gemfibrozil and
lovastatin in 30 patients with
familial combined hyperlipidemia (FCHL) in a randomized, double-blind, placebo-controlled crossover study including 8-week courses of one
drug followed by a washout period and a crossover phase to the alternate
drug. After completion of the trial, open-label combination
therapy was given for up to 12 months.
Lovastatin was more efficacious than
gemfibrozil in the reduction of total
cholesterol (23% v. 9%, P<.001) and
low-density lipoprotein (
LDL) cholesterol (28% v. 2%, P<.001), whereas
gemfibrozil surpassed
lovastatin in the reduction of
triglycerides (48% v. 0%, P<.001) and
very-low-density lipoprotein (
VLDL) cholesterol (50% v. 19%, P = .005) and the increase of
high-density lipoprotein (
HDL) cholesterol (18% v. 4%, P = .005).
Lovastatin caused a greater decline in total
apolipoprotein B (
apo B) and
LDL apo B than
gemfibrozil, whereas VLDL
apo B decreased only after
gemfibrozil therapy.
Drug-induced changes in
lipoprotein composition indicated that
gemfibrozil reduced both the number and size of VLDL particles and
lovastatin decreased the number of
LDL particles. Combined treatment was safe and had additive effects on
lipids, causing significant (P<.001) reductions in total
cholesterol (32%),
triglycerides (51%),
LDL cholesterol (34%), and
apo B (26%) and an increase in
HDL cholesterol (19%). Target
LDL cholesterol levels were achieved only in 11% of patients given
gemfibrozil alone and
triglycerides decreased to target levels in 22% after
lovastatin alone, whereas combined
therapy normalized both
lipid fractions in 96% of patients. Thus, in FCHL,
gemfibrozil has no effect on
LDL cholesterol levels but favorably influences the putative atherogenic alterations of
lipoprotein composition that are related to
hypertriglyceridemia. Conversely,
lovastatin markedly decreases
LDL cholesterol but has little effect on
triglyceride-rich
lipoproteins. Combination treatment safely corrects all of the
lipid abnormalities in most patients.