Comparison of effects of ezetimibe/simvastatin versus simvastatin versus atorvastatin in reducing C-reactive protein and low-density lipoprotein cholesterol levels.
The lowering effects of ezetimibe/simvastatin combination therapy on low-density lipoprotein (LDL) cholesterol and high-sensitivity C-reactive protein (CRP) were compared with those of simvastatin or atorvastatin monotherapy in a large cohort of patients with primary hypercholesterolemia. To compare ezetimibe/simvastatin with simvastatin, data were combined from 3 identical, prospective 12-week trials in which patients were randomized to receive placebo; ezetimibe 10 mg; ezetimibe 10 mg added to simvastatin 10, 20, 40, or 80 mg; or simvastatin 10, 20, 40, or 80 mg. To compare ezetimibe/simvastatin with atorvastatin, data were analyzed from a phase III double-blind, active-controlled study in which patients were randomized equally to receive ezetimibe/simvastatin 10/10, 10/20, 10/40, or 10/80 mg or atorvastatin 10, 20, 40, or 80 mg for 6 weeks. When averaged across doses, ezetimibe/simvastatin produced significantly greater reductions compared with simvastatin alone in LDL cholesterol (52.5% vs 38.0%, respectively) and CRP levels (31.0% vs 14.3%, respectively). At each individual simvastatin dose, co-administration with ezetimibe produced significant further CRP reductions versus simvastatin alone. Ezetimibe/simvastatin was significantly more effective at lowering LDL cholesterol than atorvastatin when pooled across doses (53.4% vs 45.3%, respectively) and in each milligram-equivalent dose comparison. Reductions in CRP of similar magnitude were observed with ezetimibe/simvastatin and atorvastatin when averaged across doses and at each milligram-equivalent statin dose comparison. In conclusion, the lipid-modulating and anti-inflammatory effects of ezetimibe/simvastatin provide additional benefits not realized by statin monotherapy alone.
Pearson
Thomas
T
University of Rochester School of Medicine and Dentistry, Rochester, New York, USA. thomas_pearson@urmc.rochester.edu
Ballantyne
Christie
C
Sisk
Christine
C
Shah
Arvind
A
Veltri
Enrico
E
Maccubbin
Darbie
D
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069059:Atorvastatin; D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000187:drug effects*; D008078:Cholesterol, LDL / Q000187:drug effects*; D004311:Double-Blind Method; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D006538:Heptanoic Acids; D011758:Pyrroles; D002097:C-Reactive Protein; D000069059:Atorvastatin; D019821:Simvastatin