COMPARISON OF THE EFFECT OF FLUVASTATIN, AN HYDROXYMETHYL GLUTARYL COENZYME-A REDUCTASE INHIBITOR, AND CHOLESTYRAMINE, A BILE-ACID SEQUESTRANT, ON LIPOPROTEIN PARTICLES DEFINED BY APOLIPOPROTEIN COMPOSITION

In a double-blind, parallel-group, randomized study, the effects of fluvastatin (FLUV) 20 and 40 mg/d on lipoprotein particle levels were compared with those of cholestyramine (CME) 16 g/d. Lipoparticles were defined by apolipoprotein composition as either those containing both apolipoprotein (apo) B and apo E or CIII (lipoprotein [Lp] E-B or Lp CIII-B) or those containing apo Al alone (Lp Al) or in association with apo All (Lp Al-All). After an Ii-week dietary stabilization period, 100 hypercholesterolemic patients were treated with FLUV 20 mg/d for 6 weeks and 40 mg/d for an additional 6 weeks and were compared with 48 hypercholesterolemic subjects treated with CME 16 g/d. Treatment with FLUV (40 mg/d) or CME (16 g/d) for 12 weeks was associated with a significant reduction in plasma cholesterol and low-density lipoprotein (LDL) cholesterol and a significant increase in high-density lipoprotein (HDL) cholesterol: However, plasma triglyceride levels decreased following FLUV treatment, whereas they increased with CME. These changes were associated with a significant reduction in the levels of apo B (FLUV, -24%, P<.001; CME, -26%, P<.001), apo E (FLUV, -36%, P<.001; CME, -32%, P<.001), and apo CIII (FLUV, -21%, P <.001; CME, -6%, NS). The decreased levels of apo E and apo CIII were mainly due to a decrease in the apo B-containing fraction as assessed by the decrease in apo E (FLUV, -40%, P <.001; CME, -24.4%, P <.001) and apo CIII (FLUV, -50%, P <.05; CME, -33%, NS) that coprecipitated with apo B-containing lipoproteins and by the decrease in plasma levels of Lp E-B (FLUV, -25.8%, P <.001; CME, 2.3%, NS) and Lp CIII-B (FLUV, -48.8%, P <.001; CME. -34.1%, P <.001). With regard to apo Al-containing particles, significant effects were observed. Treatment with FLUV or CME increased plasma levels of apo Al (FLUV, +4.7%, P <.001; CME, +8.7%, P <.001) and Lp Al (FLUV, +10%, P <.001; CME, +25.5%, P <.001) and decreased Lp Al-All (FLUV. -5.7%, NS; CME, -11.5%, P <.05). FLUV or CME decreased apo E bound to HDL (-36.8%, P <.001, and -50%, P <.001, respectively). In summary, treatment with FLUV or CME was associated with beneficial changes in plasma lipid, lipoprotein, apolipoprotein, and lipoparticle levels. FLUV is more efficient in reducing levels of atherogenic apo B-containing particles, whereas CME has a greater effect in increasing the levers of Lp Al. Copyright (C) 1995 by W.B. Saunders Company