Effect of Pravastatin in the Treatment of Patients with Type III Hyperlipoproteinemia.
OBJECTIVE: To determine the efficacy and safety of pravastatin in the treatment of subjects with Type III hyperlipoproteinemia. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SETTING: Four lipid research clinics in the United States. PATIENTS: Twenty subjects between 18 and 70 years old with three diagnostic features of Type III hyperlipoproteinemia: very-low-density lipoprotein cholesterol (VLDL-C)/total plasma triglyceride ratio in excess of 0.30; beta-migrating VLDL pattern on agarose-gel electrophoresis; and the homozygous apolipoprotein E phenotype E(2)/E(2). After 4 weeks of dietary control, the subjects were eligible if their mean plasma total cholesterol level was at least 250 mg/dl and mean plasma trigylceraide level was at least 220 mg/dL. INTERVENTIONS: Subjects were randomly assigned to pravastatin 40 mg hs or placebo hs at the start of the first 6-week double-blind treatment period. After completing this phase, subjects entered a 4-week placebo/drug washout phase before crossing over to the opposite treatment for the second 6-week double-blind treatment period. MEASUREMENTS: Plasma VLDL-C and low density lipoprotein cholesterol (LDL-C) after ultracentrifugation and total triglyceride, cholesterol and high-density lipoprotein cholesterol (HDL-C) after 6 weeks of treatment; adverse clinical events and abnormal laboratory results. RESULTS: After 6 weeks of pravastatin theraphy, plasma levels of VLDL-C and LDL-C decreased 49% and 39%, respectively (p less-than-or-equal 0.01 vs. placebo). Total cholesterol and triglyceride concentrations decreased 36% and 22%, respectively (p less-than-or-equal 0.001 vs. placebo). Levels of HDL-C increased 8% (p less-than-or-equal 0.01 vs. placebo). Pravastatin was tolerated well. One marked laboratory abnormality, an asymptomatic elevation of creatine phosphokinase, resolved upon completing pravastatin treatment. CONCLUSIONS: Pravastatin lowers plasma VLDL-C, LDL-C, total cholesterol, and triglyceride and raises HDL-C in subjects with Type III hyperlipoproteinemia. The safety profile is excellent. Pravastatin reductase inhibitor therapy affords a useful approach to the management of Type III or remnant removal disease.
Knopp
Robert H.
RH
Northwest Lipid Research Center, University of Washington, Seattle, WA.
Illingworth
D. Roger
DR
Stein
Evan A.
EA
Ginsberg
Henry N.
HN
Broyles
Frances E.
FE
Behounek
Bruce D.
BD