Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia.
OBJECTIVE
To examine the efficacy and safety of colesevelam hydrochloride, a novel, nonsystemic, lipid-lowering agent, when coadministered with starting doses of simvastatin in a multicenter, randomized, double-blind, placebo-controlled trial.


METHODS
Subjects with hypercholesterolemia (plasma low density lipoprotein [LDL] cholesterol level > 160 mg/dL and triglyceride level < or = 300 mg/dL) were randomly assigned to receive daily doses of placebo (n = 33), colesevelam 3.8 g (recommended dose, n = 37), simvastatin 10 mg (n = 35), colesevelam 3.8 g with simvastatin 10 mg (n = 34), colesevelam 2.3 g (low dose, n = 36), simvastatin 20 mg (n = 39), or colesevelam 2.3 g with simvastatin 20 mg (n = 37), for 6 weeks.


RESULTS
Mean LDL cholesterol levels decreased relative to baseline in the placebo group (P < 0.05) and in all active treatment groups (P < 0.0001). For groups treated with combination therapy, the mean reduction in LDL cholesterol level was 42% (-80 mg/dL; P < 0.0001 compared with baseline), which exceeded the reductions for simvastatin 10 mg (-26%, -48 mg/dL) or 20 mg (-34%, -61 mg/dL) alone, or for colesevelam 2.3 g (-8%, -17 mg/dL) or 3.8 g (-16%, -31 mg/dL) alone (P < 0.001). The effects of combination therapy on serum HDL cholesterol and triglyceride levels were similar to those for simvastatin alone. Side effects were similar among treatment groups, and there were no clinically important changes in laboratory parameters.


CONCLUSIONS
Coadministration of colesevelam and simvastatin was effective and well tolerated, providing additive reductions in LDL cholesterol levels compared with either agent alone.
Knapp
H H
HH
Lipid Research Clinic, University of Iowa, Iowa City USA.
Schrott
H
H
Ma
P
P
Knopp
R
R
Chin
B
B
Gaziano
J M
JM
Donovan
J M
JM
Burke
S K
SK
Davidson
M H
MH
D000328:Adult; D000368:Aged; D000499:Allylamine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001053:Apolipoproteins / Q000097:blood; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D000069472:Colesevelam Hydrochloride; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001053:Apolipoproteins; D002756:Cholagogues and Choleretics; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D014280:Triglycerides; D000499:Allylamine; D019821:Simvastatin; D000069472:Colesevelam Hydrochloride