Department of Vascular Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Lipid Clinic Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil; Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
Atherosclerosis. 2020 Oct;311:13-19. doi: 10.1016/j.atherosclerosis.2020.08.004. Epub 2020 Aug 29.
Infusion of high-density lipoprotein (HDL) mimetics failed to induce regression of atherosclerosis in recent randomized clinical trials. However, patients in these previous trials had normal levels of HDL-cholesterol, which potentially limited efficacy. Patients with very low levels of HDL-cholesterol and impaired cholesterol efflux capacity can be expected to derive the most potential benefit from infusion of HDL mimetics. This randomized clinical trial evaluated the efficacy of infusions of the HDL mimetic CER-001 in patients with genetically determined very low levels of HDL cholesterol.
In this multicenter, randomized clinical trial, we recruited patients with familial hypoalphalipoproteinemia (due to ABCA1 and/or APOA1 loss-of-function variants). Participants were randomized to intravenous infusions of 8 mg/kg CER-001 or placebo (2:1 ratio), comprising 9 weekly infusions followed by infusions every two weeks. Patients underwent repeated 3T-MRI to assess mean vessel wall area and F-FDG PET/CT to quantify arterial wall inflammation.
A total of 30 patients with a mean age of 52.7 ± 7.4 years and HDL-cholesterol of 0.35 ± 0.25 mmol/L were recruited. After 24 weeks, the absolute change in mean vessel wall area was not significantly different in the CER-001 group compared with placebo (n = 27; treatment difference: 0.77 mm, p = 0.21). Furthermore, there was no significant difference in carotid arterial wall inflammation (n = 24, treatment difference: 0.10 target-to-background ratio of the most diseased segment, p = 0.33) after 24 weeks.
In patients with genetically determined very low HDL-cholesterol, 24 weeks of treatment with HDL mimetic CER-001 did not reduce carotid vessel wall dimensions or arterial wall inflammation, compared with placebo.
在最近的随机临床试验中，富含高密度脂蛋白（HDL）的模拟物的输注未能诱导动脉粥样硬化消退。然而，这些先前试验中的患者 HDL-胆固醇水平正常，这可能限制了疗效。HDL 模拟物输注最有可能从极低水平的 HDL-胆固醇和胆固醇外排能力受损的患者中获益。这项随机临床试验评估了 HDL 模拟物 CER-001 在遗传性极低 HDL-胆固醇水平的患者中的疗效。
在这项多中心、随机临床试验中，我们招募了家族性低α脂蛋白血症（由于 ABCA1 和/或 APOA1 功能丧失变异）的患者。参与者被随机分配到静脉输注 8mg/kg 的 CER-001 或安慰剂（2:1 比例），包括 9 次每周输注，然后每两周输注一次。患者接受重复 3T-MRI 评估平均血管壁面积和 F-FDG PET/CT 量化动脉壁炎症。
共招募了 30 名平均年龄为 52.7±7.4 岁且 HDL-胆固醇为 0.35±0.25mmol/L 的患者。24 周后，与安慰剂相比，CER-001 组平均血管壁面积的绝对变化无显著差异（n=27；治疗差异：0.77mm，p=0.21）。此外，在 24 周时，颈动脉动脉壁炎症也没有显著差异（n=24，治疗差异：最病变节段的 0.10 个目标与背景比值，p=0.33）。
与安慰剂相比，在遗传性极低 HDL-胆固醇的患者中，24 周的 HDL 模拟物 CER-001 治疗并未减少颈动脉血管壁尺寸或动脉壁炎症。
