Clinical Efficacy and Tolerability of Ezetimibe in Combination With Atorvastatin in Japanese Patients With Hypercholesterolemia-Ezetimibe Phase IV Randomized Controlled Trial in Patients With Hypercholesterolemia

Tamio Teramoto, Teruo Sawada, Kazuya Iwamoto, Hiroyuki Daida, Tamio Teramoto, Teruo Sawada, Kazuya Iwamoto, Hiroyuki Daida

Abstract

Objective: The purpose of this study was to compare the efficacy and tolerability of combination therapy of ezetimibe and atorvastatin in patients with high LDL cholesterol that had not reached the lipid management target value with 10 mg atorvastatin monotherapy, against increasing the dose to 20 mg atorvastatin or switching to 2.5 mg rosuvastatin.

Design setting and participants: This was an open-label, randomized, multicenter, 3-parallel-group comparison trial at 23 community hospitals and clinics in Japan (enrollment period March 2009 to May 2010) in 125 patients with high LDL cholesterol.

Interventions: A total of 125 Japanese patients with high LDL cholesterol level were randomized to 1 of the following 3 treatment groups: the ezetimibe (10 mg/d) and atorvastatin (10 mg/d) group, the atorvastatin (20 mg/d) group, or the rosuvastatin (2.5 mg/d) group for 12 weeks after treatment with 10 mg atorvastatin alone for 4 weeks.

Main outcome measure: Percent change in LDL cholesterol level from baseline (4 weeks after treatment with 10 mg atorvastatin alone) until study completion.

Results: The percent change in LDL cholesterol level from baseline until study completion was statistically greater for the combination of 10 mg ezetimibe + 10 mg atorvastatin compared with increasing atorvastatin to 20 mg (-25.8% vs -15.1%; P < 0.0001). A similar result was observed for ezetimibe + atorvastatin compared with switching to 2.5 mgt rosuvastatin (-25.8% vs 0.8%; P < 0.0001). The proportion of patients who reached the target LDL cholesterol value with the combination of ezetimibe + atorvastatin was significantly higher than increasing atorvastatin and switching to rosuvastatin (78.7%, 41.3%, and 3.1%, respectively). Although 5 serious adverse experiences bearing no relation to the study medications were reported, there were no adverse reactions.

Conclusions: The combination of 10 mg ezetimibe +10 mg atorvastatin was more effective than increasing atorvastatin to 20 mg or switching to 2.5 mg rosuvastatin in patients with hypercholesterolemia whose LDL cholesterol levels had not reached the recommended target value with 10 mg atorvastatin monotherapy for 4 weeks. Ezetimibe coadministration with atorvastatin was well tolerated. ClinicalTrials.gov identifier: NCT00871351.

Keywords: LDL cholesterol; atorvastatin; clinical trial; ezetimibe; hypercholesterolemia; rosuvastatin.