Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial.
BACKGROUND
Despite the established efficacy of statins, many patients do not achieve recommended LDL cholesterol (LDL-C) goals. Contributing factors may be inadequate dosing, increased risk for adverse effects with high-dose monotherapy, and increased potential for intolerance and adverse effects with combinations of available agents.


RESULTS
In a double-blind study, 628 patients with baseline LDL-C 145 to 250 mg/dL and triglycerides < or =350 mg/dL were randomly assigned to receive 1 of the following for 12 weeks: ezetimibe (10 mg/d); atorvastatin (10, 20, 40, or 80 mg/d); ezetimibe (10 mg) plus atorvastatin (10, 20, 40, or 80 mg/d); or placebo. The primary efficacy end point was percentage reduction in LDL-C for pooled ezetimibe plus atorvastatin versus pooled atorvastatin treatment groups. Ezetimibe plus atorvastatin significantly improved LDL-C, HDL cholesterol (HDL-C), triglycerides, total cholesterol:HDL-C, and high-sensitivity C-reactive protein (hs-CRP) compared with atorvastatin alone (P<0.01). Coadministration of ezetimibe provided a significant additional 12% LDL-C reduction, 3% HDL-C increase, 8% triglyceride reduction, and 10% hs-CRP reduction versus atorvastatin alone. Ezetimibe plus atorvastatin provided LDL-C reductions of 50% to 60%, triglyceride reductions of 30% to 40%, and HDL-C increases of 5% to 9%, depending on atorvastatin dose. LDL-C reductions with ezetimibe plus 10 mg atorvastatin (50%) and 80 mg atorvastatin alone (51%) were similar.


CONCLUSIONS
Ezetimibe plus atorvastatin was well tolerated, with a safety profile similar to atorvastatin alone and to placebo. When coadministered with atorvastatin, ezetimibe provided significant incremental reductions in LDL-C and triglycerides and increases in HDL-C. Coadministration of ezetimibe and atorvastatin offers a well-tolerated and highly efficacious new treatment option for patients with hypercholesterolemia.
Ballantyne
Christie M
CM
Baylor College of Medicine, 6565 Fannin Street, MS A-601, Houston, Tex 77030, USA. cmb@bcm.tmc.edu
Houri
John
J
Notarbartolo
Alberto
A
Melani
Lorenzo
L
Lipka
Leslie J
LJ
Suresh
Ramachandran
R
Sun
Steven
S
LeBeaut
Alexandre P
AP
Sager
Philip T
PT
Veltri
Enrico P
EP
D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069059:Atorvastatin; D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects; D002097:C-Reactive Protein / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004064:Digestive System / Q000187:drug effects; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000139:chemically induced; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001384:Azetidines; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D002097:C-Reactive Protein; D000069059:Atorvastatin; D000069438:Ezetimibe