1 Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
2 Division of Cardiology, Department of Medicine, University of Chicago, Chicago, IL, USA.
J Cardiovasc Pharmacol Ther. 2019 Jan;24(1):54-61. doi: 10.1177/1074248418780733. Epub 2018 Jun 25.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is expressed in multiple tissues, including the small intestine. The effect of PCSK9 inhibition on cholesterol absorption is not known.
Measure serum cholesterol absorption markers before and after initiation of PCSK9 inhibitors.
Single-center retrospective cohort of patients administered evolocumab and alirocumab between July 2015 and January 2017. Paired t tests were used to compare mean serum cholesterol marker concentrations, and ratios to total cholesterol, before and after PCSK9 inhibitor initiation. Analyses were repeated for those taking and not taking statins and taking or not taking ezetimibe at both initiation and follow-up, for each PCSK9 inhibitor, and based on follow-up time (<60, 60-120, and >120 days).
There were 62 possible participants, 34 were excluded for lack of data or unknown PCSK9 inhibitor initiation date. Average follow-up was 92.5 days. Mean campesterol (before 3.14 μg/mL, 95% CI: 2.79-4.38 μg/mL; after 2.09 μg/mL, 95% CI: 1.87-2.31 μg/mL; P < .0001), sitosterol (before 2.46 μg/mL, 95% CI: 2.23-2.70 μg/mL; after 1.62 μg/mL, 95% CI: 1.48-1.75 μg/mL; P < .0001), and cholestanol (before 3.25 μg/mL, 95% CI: 3.04-3.47 μg/mL; after 2.08 μg/mL, 95% CI: 1.96-2.21 μg/mL; P < .0001) all significantly decreased at follow-up. There was no significant change in absorption marker to total cholesterol ratios. Findings were not influenced by statin or ezetimibe use or nonuse, which PCSK9 inhibitor was prescribed, or time to follow-up.
Proprotein convertase subtilisin/kexin type 9 inhibition was associated with decreased cholesterol absorption markers.
前蛋白转化酶枯草溶菌素 9（PCSK9）在多种组织中表达，包括小肠。PCSK9 抑制对胆固醇吸收的影响尚不清楚。
测量开始使用 PCSK9 抑制剂前后的血清胆固醇吸收标志物。
2015 年 7 月至 2017 年 1 月期间，对在单一中心接受依洛尤单抗和阿利西尤单抗治疗的患者进行回顾性队列研究。采用配对 t 检验比较 PCSK9 抑制剂起始前后血清胆固醇标志物浓度及其与总胆固醇的比值。对于每个 PCSK9 抑制剂，以及基于随访时间（<60、60-120 和>120 天），重复分析了起始和随访时同时服用和不服用他汀类药物以及同时服用和不服用依折麦布的患者。
共有 62 名符合条件的患者，34 名因缺乏数据或未知 PCSK9 抑制剂起始日期而被排除在外。平均随访时间为 92.5 天。坎培西醇（起始前 3.14μg/mL，95%CI：2.79-4.38μg/mL；起始后 2.09μg/mL，95%CI：1.87-2.31μg/mL；P<0.0001）、豆甾醇（起始前 2.46μg/mL，95%CI：2.23-2.70μg/mL；起始后 1.62μg/mL，95%CI：1.48-1.75μg/mL；P<0.0001）和胆甾烷醇（起始前 3.25μg/mL，95%CI：3.04-3.47μg/mL；起始后 2.08μg/mL，95%CI：1.96-2.21μg/mL；P<0.0001）均显著降低。吸收标志物与总胆固醇的比值无明显变化。他汀类药物或依折麦布的使用或不使用、所开的 PCSK9 抑制剂以及随访时间均未影响研究结果。
PCSK9 抑制与胆固醇吸收标志物降低有关。
