Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, USA.
TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
J Clin Lipidol. 2022 Jul-Aug;16(4):538-543. doi: 10.1016/j.jacl.2022.05.069. Epub 2022 Jun 6.
LDL-C is the pivotal risk factor for atherosclerotic cardiovascular disease, and the benefit from LDL-C lowering is proportional to the magnitude of reduction. Clinical trials demonstrate that evolocumab reduces LDL-C levels by approximately 60% when measured at the trough of drug effect, which may underestimate cumulative LDL-C reduction. We obtained a time-averaged estimate of LDL-C lowering that included both peaks and troughs. Pooled analysis of 5 phase 2 trials included patients with hypercholesterolemia who received placebo or evolocumab (140 mg every 2 weeks [Q2W] or 420 mg monthly [QM]). Percent changes from baseline LDL-C and free serum PCSK9 were averaged across weeks 9-12. In 372 patients, time-averaged percent reduction from baseline in LDL-C with evolocumab vs placebo was 67.6% (95% CI: 63.9-71.3) with Q2W dosing and 65.0% (95% CI: 60.7-69.3) with QM dosing. The time-averaged measure yielded LDL-C reductions for evolocumab that exceeded measurements at the end of dosing intervals and may provide a better estimate of cardiovascular benefit during long-term therapy.
LDL-C 是动脉粥样硬化性心血管疾病的关键风险因素，LDL-C 降低的获益与降低幅度成正比。临床试验表明，依洛尤单抗在药物作用的最低点测量时可使 LDL-C 水平降低约 60%，这可能低估了 LDL-C 的累计降低。我们获得了一个时间平均的 LDL-C 降低估计值，包括峰值和谷值。5 项 2 期临床试验的汇总分析纳入了接受安慰剂或依洛尤单抗治疗的高胆固醇血症患者（每 2 周 140mg[Q2W]或每月 420mg[QM]）。从基线 LDL-C 和游离血清 PCSK9 的百分比变化在第 9-12 周进行平均。在 372 名患者中，依洛尤单抗与安慰剂相比，LDL-C 的时间平均降低百分比为 67.6%（95%CI：63.9-71.3），Q2W 给药组为 65.0%（95%CI：60.7-69.3）。时间平均测量值使依洛尤单抗的 LDL-C 降低幅度超过了给药间隔结束时的测量值，可能更准确地估计长期治疗期间的心血管获益。
