Atorvastatin with or without an Antibody to PCSK9 in Primary Hypercholesterolemia
Atorvastatin with or without an Antibody to PCSK9 in Primary Hypercholesterolemia
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DOI：
10.1056/nejmoa1201832
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发表时间：
2012-11-15
影响因子：
158.5
通讯作者：
Stein, Evan A.
中科院分区：
文献类型：
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作者：
Roth, Eli M.;McKenney, James M.;Stein, Evan A.
血清前蛋白转化酶枯草杆菌蛋白酶/kexin 9（PCSK 9）与低密度脂蛋白（LDL）受体结合，增加LDL受体的降解，降低LDL胆固醇从循环中清除的速率。REGN727/SAR236553（在此指定为SAR 236553），一种全人PCSK 9单克隆抗体，增加LDL受体的再循环并降低LDL胆固醇水平。一项安慰剂对照试验，涉及92名LDL胆固醇水平<100 mg/dl的患者（2.6 mmol/L）或更高。患者被随机分配接受8周治疗，每日80 mg阿托伐他汀+每2周一次SAR 236553，每日10 mg阿托伐他汀+每2周一次SAR 236553，或80 mg阿托伐他汀每日一次加安慰剂每2周一次，并在治疗后再随访8周。与80 mg阿托伐他汀+安慰剂相比，80 mg阿托伐他汀+SAR 236553组LDL胆固醇较基线降低的百分比为73.2 +/-3.5（P
BACKGROUNDSerum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels.METHODSWe performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to receive 8 weeks of treatment with 80 mg of atorvastatin daily plus SAR236553 once every 2 weeks, 10 mg of atorvastatin daily plus SAR236553 once every 2 weeks, or 80 mg of atorvastatin daily plus placebo once every 2 weeks and were followed for an additional 8 weeks after treatment.RESULTSThe least-squares mean (+/- SE) percent reduction from baseline in LDL cholesterol was 73.2 +/- 3.5 with 80 mg of atorvastatin plus SAR236553, as compared with 17.3 +/- 3.5 with 80 mg of atorvastatin plus placebo (P