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


CONCLUSIONS
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.
Ballantyne
Christie M
CM
Methodist DeBakey Heart Center, Houston, Texas, USA. cmb@bcm.tmc.edu
Miller
Elinor
E
Chitra
Rohini
R
D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D002792:Cholestyramine Resin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D002792:Cholestyramine Resin; D000068718:Rosuvastatin Calcium