Fluvastatin reduces levels of plasma apo B-containing particles and increases those of LpA-I. European Fluvastatin Study Group

Abstract

Epidemiologic studies have demonstrated an association between apolipoprotein (apo) B-containing particles (lipoprotein [Lp] E:B; LpC-III:B) and an inverse association between LpA-I and the risk of coronary artery disease (CAD). The effect of 6 weeks of treatment with fluvastatin (20 and 40 mg/day in the evening), a novel competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, on lipoparticle levels was studied in 423 patients with hypercholesterolemia after 14 weeks of standard dietary therapy. The combined data of the European double-blind controlled studies were used for the analysis. Two independent groups of hypercholesterolemic patients receiving fluvastatin (20 and 40 mg every evening) for 6 weeks were compared with a placebo group. For inclusion, patients had to fulfill the following criteria: plasma low-density lipoprotein (LDL) cholesterol levels > 160 mg/dL and premature CAD and/or two associated risk factors; LDL cholesterol > 190 mg/dL and no CAD; triglycerides < 300 mg/dL. All measurements were performed at the Pasteur Institute Central Laboratory, LpE:B and LpC-III:B were measured by double-site ELISA. Lipoprotein A-I and LpA-I:A-II were determined by differential electroimmunodiffusion. Treatment with 20 and 40 mg of fluvastatin was associated with reductions in plasma apo B (median change: -19.3% and -22.8%, respectively; p < 0.001), LpE:B (-12.5% and -22.6%, respectively; p < 0.001), and LpC-III:B (-3.6% and -36.8%, respectively; p < 0.001) particles compared with placebo. Significant increases in plasma apo A-I (1.7% and 4.8%, respectively; p < 0.001) and antiatherogenic LpA-I (2.3% and 6.9%, respectively; p < 0.001) were also observed. Levels of LpA-I:A-II were not affected by fluvastatin treatment. In conclusion, 6-week treatment with fluvastatin is associated with beneficial antiatherogenic changes in lipoparticle profiles in hypercholesterolemic patients.