A randomized, double-blind, placebo-controlled trial showed that inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL cholesterol levels to a median of 30 mg per deciliter (0.78 mmol per liter) and reduced the risk of cardiovascular disease (CVD). The trial included 27,564 patients with atherosclerotic CVD and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive s.c. evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo. The median duration of follow-up was 2.2 years. At 48 weeks, the LDL cholesterol levels were significantly reduced from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter). Relative to placebo, evolocumab treatment significantly reduced the risk of the primary end point (the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization, 1344 patients [9.8%] vs. 1563 patients [11.3%]; hazard ratio, 0.85) and the key secondary end point (the composite of cardiovascular death, myocardial infarction, or stroke, 816 [5.9%] vs. 1013 [7.4%]; hazard ratio, 0.80). The results were consistent across key subgroups, including the subgroup of patients in the lowest quartile for baseline LDL cholesterol levels (median, 74 mg per deciliter [1.9 mmol per liter]). There was no significant difference between the study groups with regard to adverse events (including new-onset diabetes and neurocognitive events). The findings suggest that lowering of LDL cholesterol levels below current targets is safe and effective for patients with atherosclerotic CVD. Source: http://www.nejm.org/
一项随机，双盲，安慰剂对照试验显示，在他汀类药物治疗基础上用evolocumab抑制PCSK9将低密度脂蛋白胆固醇水平降低至中值为30mg / dl（0.78mmol / l）并降低心血管病风险。该试验包括27,564例接受他汀类药物治疗的动脉粥样硬化性心血管病患者，低密度脂蛋白胆固醇水平为70毫克/分升（1.8毫摩尔/升）或更高。患者被随机分配接受皮下注射evolocumab（每2周140mg或每月420mg）或匹配安慰剂。中位随访持续时间为2.2年。在48周时，低密度脂蛋白胆固醇水平从中值基线值92mg /分升（2.4mmol /升）显着降低至30mg /分升（0.78mmol /升）。相对于安慰剂，evolocumab治疗显着降低了主要终点（包括心血管死亡，心肌梗塞，中风，因不稳定型心绞痛住院或冠脉血运重建的风险，分别为1344例[9.8％]与1563例[11.3％] ;风险比0.85）和关键次要终点（包括心血管死亡，心肌梗塞或中风，分别为816 [5.9％]与1013 [7.4％]例;风险比0.80）。关键亚组的结果一致，包括基线低密度脂蛋白胆固醇水平最低四分位数的患者亚组（中值每分升74毫克[1.9mmol /升]）。各组间不良事件（包括新发糖尿病和神经认知事件）无显着差异。结果提示，降低低密度脂蛋白胆固醇水平至低于目前的目标对动脉粥样硬化性心血管病患者安全，有效。来源：http://www.nejm.org/