Efficacy and safety of rosuvastatin alone and in combination with cholestyramine in patients with severe hypercholesterolemia: a randomized, open-label, multicenter trial

Abstract

Background: Patients with severe hypercholesterolemia may need greater cholesterol reductions than can be achieved with statin therapy alone.

Objective: The primary objective of this trial was to compare the efficacy of a combination of rosuvastatin plus cholestyramine with that of rosuvastatin alone for reducing low-density lipoprotein cholesterol (LDL-C) levels after 6 weeks of treatment.

Methods: In this open-label, multicenter, randomized, parallel-group, comparator trial, adult patients with severe hypercholesterolemia (LDL-C level, 190-400 mg/dL) received rosuvastatin 40 mg/d for 6 weeks after a 6-week dietary lead-in period and were then randomized to 6 weeks of treatment with rosuvastatin 80 mg/d alone or rosuvastatin 80 mg/d plus cholestyramine 16 g/d (8 g BID with meals).

Results: Of 153 eligible patients, 147 (83 men, 64 women; mean [SD] age, 54.5 [13.7] years; mean [SD] bodyweight, 81.3 [14.4] kg) received randomized treatment, and 144 had post baseline measurements and were included in the analysis. The mean (SD) reduction in LDL-C was 522% (13.0%) after treatment with rosuvastatin 40 mg, and the least squares mean (SE) reductions in LDL-C were 56.4% (1.8%) and 60.5% (1.8%) after treatment with rosuvastatin 80 mg alone (n = 69) and rosuvastatin 80 mg plus cholestyramine (n = 75), respectively. No significant differences between treatments were found for these or other lipid measurements. Incremental LDL-C reductions >30% were obtained in 29% (22/75) of patients receiving combination therapy and 4% (3/69) of patients receiving rosuvastatin alone. The combination therapy was less well tolerated, primarily due to gastrointestinal symptoms; otherwise, the treatments were generally well tolerated.

Conclusion: In this group of patients with severe hypercholesterolemia, the combination of rosuvastatin 80 mg with cholestyramine 16 g/d did not provide a significantly greater efficacy benefit than rosuvastatin alone.