Shinji Koba1, Ikuo Inoue2, Marcoli Cyrille3, Chen Lu3, Hyoe Inomata4, Junichiro Shimauchi4, Kouji Kajinami5. 1. Department of Medicine, Division of Cardiology, Showa University School of Medicine. 2. Department of Endocrinology and Diabetes, Saitama Medical University. 3. Amgen Inc., Thousand Oaks. 4. Amgen Astellas BioPharma K.K. 5. Department of Cardiology, Kanazawa Medical University.
Abstract
AIM: In patients with hyperlipidemia, intolerance to statins presents a challenge in reducing the risk of events associated with cardiovascular disease. This phase 3, randomized, double-blind trial in Japanese patients with statin intolerance aimed to evaluate the efficacy and safety of evolocumab vs. ezetimibe in lowering low-density lipoprotein-cholesterol (LDL-C). METHODS: This study was conducted in a 12-week, double-blind period followed by an open-label extension designed to characterize 1 year of evolocumab treatment. Statin intolerance was defined as failure of two or more statins due to myalgia, myositis, or rhabdomyolysis. Eligible patients were randomized at 2:2:1:1 into four groups: 420 mg evolocumab every 4 weeks (Q4W)＋oral placebo daily, 140 mg evolocumab every 2 weeks (Q2W)＋oral placebo daily, subcutaneous (SC) placebo Q4W＋10 mg ezetimibe daily, and SC placeboQ2W＋ 10 mg ezetimibe daily. RESULTS: Sixty-one patients were randomized to evolocumab (n=40) or ezetimibe (n=21). For the co-primary endpoints of percent change from the baseline in mean LDL-C to the mean of weeks 10 and 12 and to week 12, the evolocumab-ezetimibe treatment differences were -39.4% (95% CI, -47.2% to -31.5%) and -40.1% (95% CI, -48.7% to -31.6%), respectively (adjusted p＜0.0001). The most common adverse events were diarrhea (9.5%) and nasopharyngitis (12.5%) in the ezetimibe and evolocumab groups, respectively, during the double-blind period and nasopharyngitis (29%) during the open-label extension. CONCLUSION:Evolocumab was superior to ezetimibe in reducing LDL-C during the 12-week double-blind period in this population of Japanese patients with statin intolerance, with efficacy and safety results maintained for 1 year. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02634580.
RCT Entities:
AIM: In patients with hyperlipidemia, intolerance to statins presents a challenge in reducing the risk of events associated with cardiovascular disease. This phase 3, randomized, double-blind trial in Japanese patients with statin intolerance aimed to evaluate the efficacy and safety of evolocumab vs. ezetimibe in lowering low-density lipoprotein-cholesterol (LDL-C). METHODS: This study was conducted in a 12-week, double-blind period followed by an open-label extension designed to characterize 1 year of evolocumab treatment. Statin intolerance was defined as failure of two or more statins due to myalgia, myositis, or rhabdomyolysis. Eligible patients were randomized at 2:2:1:1 into four groups: 420 mg evolocumab every 4 weeks (Q4W)＋oral placebo daily, 140 mg evolocumab every 2 weeks (Q2W)＋oral placebo daily, subcutaneous (SC) placebo Q4W＋10 mg ezetimibe daily, and SC placebo Q2W＋ 10 mg ezetimibe daily. RESULTS: Sixty-one patients were randomized to evolocumab (n=40) or ezetimibe (n=21). For the co-primary endpoints of percent change from the baseline in mean LDL-C to the mean of weeks 10 and 12 and to week 12, the evolocumab-ezetimibe treatment differences were -39.4% (95% CI, -47.2% to -31.5%) and -40.1% (95% CI, -48.7% to -31.6%), respectively (adjusted p＜0.0001). The most common adverse events were diarrhea (9.5%) and nasopharyngitis (12.5%) in the ezetimibe and evolocumab groups, respectively, during the double-blind period and nasopharyngitis (29%) during the open-label extension. CONCLUSION:Evolocumab was superior to ezetimibe in reducing LDL-C during the 12-week double-blind period in this population of Japanese patients with statin intolerance, with efficacy and safety results maintained for 1 year. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02634580.
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