Metzner Thomas, Leitner Deborah R, Mellitzer Karin, Beck Andrea, Sourij Harald, Stojakovic Tatjana, Reishofer Gernot, März Winfried, Landmesser Ulf, Scharnagl Hubert, Toplak Hermann, Silbernagel Günther
Department of Internal Medicine, Division of Angiology, Medical University of Graz, 8036 Graz, Austria.
Department of Medical Affairs, Sanofi-Aventis GmbH, 1100 Vienna, Austria.
Biomedicines. 2022 Jan 17;10(1):193. doi: 10.3390/biomedicines10010193.
PCSK9 antibodies strongly reduce LDL cholesterol. The effects of PCSK9 antibodies on triglyceride metabolism are less pronounced. The present study aimed to investigate in detail the effects of alirocumab on triglycerides, triglyceride-rich lipoproteins, and lipase regulators.
A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were two visits at the study site: the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. Fat-tolerance tests, nuclear magnetic resonance spectroscopy, and enzyme-linked immunosorbent assays were performed to analyze lipid metabolism.
A total of 21 participants underwent the first and second investigation. Among these, two participants only received alirocumab twice and 19 patients completed the trial per protocol. All of them had atherosclerotic vascular disease. There was no significant effect of alirocumab treatment on fasting triglycerides, post-prandial triglycerides, or lipoprotein-lipase regulating proteins. Total, large, and small LDL particle concentrations decreased, while the HDL particle concentration increased (all < 0.001). Mean total circulating PCSK9 markedly increased in response to alirocumab treatment ( < 0.001). Whereas PCSK9 increased more than three-fold in all 19 compliant patients, it remained unchanged in those two patients with two injections only.
Significant effects of alirocumab on triglyceride metabolism were not detectable in the ALIROCKS trial. The total circulating PCSK9 concentration might be a useful biomarker to differentiate non-adherence from non-response to PCSK9 antibodies.
前蛋白转化酶枯草溶菌素9（PCSK9）抗体可显著降低低密度脂蛋白胆固醇。PCSK9抗体对甘油三酯代谢的影响则不太明显。本研究旨在详细探究阿利西尤单抗对甘油三酯、富含甘油三酯的脂蛋白及脂肪酶调节因子的影响。
共招募了24例有PCSK9抗体治疗指征的患者。在研究地点进行了两次访视：第一次在开始阿利西尤单抗治疗前，第二次在治疗10周后。进行了脂肪耐量试验、核磁共振波谱分析和酶联免疫吸附测定以分析脂质代谢。
共有21名参与者接受了首次和第二次调查。其中，两名参与者仅接受了两次阿利西尤单抗治疗，19例患者按方案完成了试验。他们均患有动脉粥样硬化性血管疾病。阿利西尤单抗治疗对空腹甘油三酯、餐后甘油三酯或脂蛋白脂肪酶调节蛋白无显著影响。总低密度脂蛋白、大低密度脂蛋白和小低密度脂蛋白颗粒浓度降低，而高密度脂蛋白颗粒浓度升高（均P<0.001）。阿利西尤单抗治疗后，平均循环PCSK9显著升高（P<0.001）。在所有19例依从性良好的患者中，PCSK9增加了三倍以上，而仅接受两次注射的两名患者中PCSK9保持不变。
在ALIROCKS试验中未检测到阿利西尤单抗对甘油三酯代谢有显著影响。循环PCSK9总浓度可能是区分对PCSK9抗体不依从与无反应的有用生物标志物。
