Changes in plasma apolipoprotein B-containing lipoparticle levels following therapy with fluvastatin and cholestyramine

Abstract

<h2>Abstract</h2> Epidemiologic studies have demonstrated that apolipoprotein (apo) B-containing lipoparticles (LpE:B, LpC-III:B) are associated with the risk of coronary artery disease whereas apo A-1-containing lipoparticles (LpA-1) are protective against coronary artery disease. The effect on lipoparticle levels of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin, in combination with cholestyramine, was assessed in a double-blind randomized study. A total of 144 patients with primary hypercholesterolemia were recruited, who had successfully completed an original study comparing the effects of fluvastatin and cholestyramine on plasma lipoparticle levels. All subjects fulfilled the following inclusion criteria: plasma low density lipoprotein cholesterol (LDL-C) levels >160 mg/dL, with premature coronary artery disease and 2 associated risk factors; or LDL-C >190 mg/dL, no coronary artery disease, and triglycerides <300 mg/dL, after a lipid-lowering diet. Patients were randomized to 1 of 3 combination therapy groups: fluvastatin 20 mg/day plus cholestyramine 4 g/day; fluvastatin 20 mg/day plus cholestyramine 8g/day; and fluvastatin 20 mg/day plus cholestyramine 16 g/day. The study length was 6 weeks and patients were examined at 3-week intervals. Fluvastatin plus cholestyramine produced a significant (p <0.001), dose-dependent reduction in levels of cholesterol (range, −29 to −34%), LDL-C (range, −30 to −44%), apo B (range, −23 to −34%), and apo E (range, −33 to −43%). LpE:B levels were also reduced (range, −19 to −26%), but not significantly. Reductions in levels of apo C-III (range, −6.7 to −21%) and LpC-III:B (range, −32 to −28%) were only statistically significant at the lower doses of cholestyramine. The combination therapy produced a clear, dose-dependent increase in apo A-1 (range, 8–14%; p <0.001) and LpA-I (range, 13–32%; p <0.001). In conclusion, treatment combining 20 mg/day of fluvastatin with cholestyramine produces a major beneficial change in the lipoprotein and coronary artery disease risk profile in hypercholesterolemic subjects, reducing the levels of atherogenic apo B—containing particles and increasing the levels of protective apo A-1-containing particles.