Circulation. 2003;107:2409-2415
Published online before print April 28, 2003, doi: 10.1161/01.CIR.0000068312.21969.C8
Published online before print April 28, 2003, doi: 10.1161/01.CIR.0000068312.21969.C8
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(Circulation. 2003;107:2409.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Effect of Ezetimibe Coadministered With Atorvastatin in 628 Patients With Primary Hypercholesterolemia
A Prospective, Randomized, Double-Blind Trial
From Baylor College of Medicine, Houston, Tex (C.M.B.); Radiant Research, Stuart, Fla (J.H.); Istituto di Medicina Interna e Geriatria, Università degli Studi, Palermo, Italy (A.N.); and Schering-Plough Research Institute, Kenilworth, NJ (L.M., L.J.L., R.S., S.S., A.P.L., P.T.S., E.P.V.).
Correspondence to Christie M. Ballantyne, MD, Baylor College of Medicine, 6565 Fannin Street, MS A-601, Houston, TX 77030. E-mail cmb{at}bcm.tmc.edu
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.
Methods and Results— In a double-blind study, 628 patients with baseline LDL-C 145 to 250 mg/dL and triglycerides 
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.
Key Words: lipoproteins • cholesterol • trials • drugs • hypercholesterolemia
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