依洛尤单抗在急性冠状动脉综合征患者中早期降低 LDL 胆固醇水平的研究（EVOPACS）。
Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS).
机构信息
Department of Cardiology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.
Department of Cardiology, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.
出版信息
J Am Coll Cardiol. 2019 Nov 19;74(20):2452-2462. doi: 10.1016/j.jacc.2019.08.010. Epub 2019 Aug 31.
BACKGROUND
Although guidelines recommend in-hospital initiation of high-intensity statin therapy in patients with acute coronary syndromes (ACS), low-density lipoprotein cholesterol (LDL-C) target levels are frequently not attained. Evolocumab, a rapidly acting, potent LDL-C-lowering drug, has not been studied in the acute phase of ACS.
OBJECTIVES
The purpose of this study was to assess the feasibility, safety, and LDL-C-lowering efficacy of evolocumab initiated during the in-hospital phase of ACS.
METHODS
The authors conducted an investigator-initiated, randomized, double-blind, placebo-controlled trial involving 308 patients hospitalized for ACS with elevated LDL-C levels (≥1.8 mmol/l on high-intensity statin for at least 4 weeks; ≥2.3 mmol/l on low- or moderate-intensity statin; or ≥3.2 mmol/l on no stable dose of statin). Patients were randomly assigned 1:1 to receive subcutaneous evolocumab 420 mg or matching placebo, administered in-hospital and after 4 weeks, on top of atorvastatin 40 mg. The primary endpoint was percentage change in calculated LDL-C from baseline to 8 weeks.
RESULTS
Most patients (78.2%) had not been on previous statin treatment. Mean LDL-C levels decreased from 3.61 to 0.79 mmol/l at week 8 in the evolocumab group, and from 3.42 to 2.06 mmol/l in the placebo group; the difference in mean percentage change from baseline was -40.7% (95% confidence interval: -45.2 to -36.2; p < 0.001). LDL-C levels <1.8 mmol/l were achieved at week 8 by 95.7% of patients in the evolocumab group versus 37.6% in the placebo group. Adverse events and centrally adjudicated cardiovascular events were similar in both groups.
CONCLUSIONS
In this first randomized trial assessing a PCSK9 antibody in the very high-risk setting of ACS, evolocumab added to high-intensity statin therapy was well tolerated and resulted in substantial reduction in LDL-C levels, rendering >95% of patients within currently recommended target levels. (EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes [EVOPACS]; NCT03287609).
背景
尽管指南建议在急性冠脉综合征（ACS）患者中进行住院期间开始高强度他汀类药物治疗，但低密度脂蛋白胆固醇（LDL-C）的目标水平经常无法达到。依洛尤单抗是一种快速作用、强效的 LDL-C 降低药物，尚未在 ACS 的急性期进行研究。
目的
本研究旨在评估依洛尤单抗在 ACS 住院期间开始治疗的可行性、安全性和 LDL-C 降低效果。
方法
作者进行了一项由研究者发起的、随机、双盲、安慰剂对照试验，纳入了 308 例因 LDL-C 水平升高（高强度他汀类药物治疗至少 4 周时≥1.8mmol/l；低或中强度他汀类药物治疗时≥2.3mmol/l；或未服用稳定剂量他汀类药物时≥3.2mmol/l）而住院治疗的 ACS 患者。患者按 1:1 随机分配接受皮下注射依洛尤单抗 420mg 或匹配安慰剂，在住院期间和 4 周后加用阿托伐他汀 40mg。主要终点是从基线到 8 周时计算的 LDL-C 的百分比变化。
结果
大多数患者（78.2%）以前未接受过他汀类药物治疗。依洛尤单抗组的 LDL-C 水平从基线时的 3.61mmol/l 降至 8 周时的 0.79mmol/l，安慰剂组从 3.42mmol/l 降至 2.06mmol/l；两组间的平均百分比变化差值为-40.7%（95%置信区间：-45.2 至-36.2；p<0.001）。依洛尤单抗组有 95.7%的患者在 8 周时 LDL-C 水平<1.8mmol/l，而安慰剂组只有 37.6%。两组的不良事件和中心裁定的心血管事件相似。
结论
在这项评估 ACS 极高危患者中 PCSK9 抗体的首次随机试验中，依洛尤单抗联合高强度他汀类药物治疗耐受性良好，可显著降低 LDL-C 水平，使>95%的患者达到目前推荐的目标水平。（EVOlocumab for Early Reduction of LDL-cholesterol Levels in Patients With Acute Coronary Syndromes [EVOPACS]；NCT03287609）。
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