目的:纯合子家族性高胆固醇血症(HoFH)是一种罕见的疾病,其特征是出生时循环低密度脂蛋白胆固醇(LDL-C)明显升高。这篇综述旨在严格评估HoFH的治疗方法的疗效。安全,可访问性,治疗途径内的整体背景和位置。
方法:进行了混合方法审查,以系统地识别和表征HoFH的主要介入研究,以LDL-C降低为主要结果。评估的干预措施是依泽替米贝,前蛋白转化酶枯草杆菌蛋白酶/kexin9型抑制剂(PCSK9i),洛米他必特,evinacumab,有或没有LDL单采。
结果:确定了26项报告独特患者数据的开创性研究。4项研究为随机对照试验(RCT),其余为单臂试验或观察注册。提取的数据是异质的,不适合进行荟萃分析。两个RCT,评估为低偏见风险,证明PCSK9i是安全和中等有效的。RCT证明,evinacumab在所有HoFH亚组中是安全有效的。据报道,Lomitapide在单臂试验中有效,但是不良事件的问题,耐受性,并确定了依从性。依泽替米贝的RCT显示,与他汀类药物联合使用时,效果中等。据报道LDL单采术有效,但是它的证据基础存在非常高的偏倚风险。所有干预措施都降低了LDL-C,但是这件事的规模,以及支持证据的确定性,varieted.
结论:在实践中,治疗HoFH需要多种治疗。这些的排序应该在个性化的基础上进行,考虑到每次干预的好处。
纯合子家族性高胆固醇血症(HoFH)是一种罕见的遗传性疾病,可导致胆固醇水平升高。这可能导致过早的心血管事件,如心脏病发作和中风。我们进行了文献综述,以系统地识别和分析有关降低胆固醇水平的HoFH的新疗法的研究。关注每种治疗方法的整体优缺点。我们确定了26项研究,包括临床试验和观察研究,报告干预措施ezetimibe,前蛋白转化酶枯草杆菌蛋白酶/kexin9型抑制剂(PCSK9i),洛米他必特,evinacumab,和低密度脂蛋白单采术。虽然所有治疗都显示出降低胆固醇水平的希望,没有一个足以有效地独自治疗HoFH,通常,研究方法的弱点限制了对结果的信心。证据表明,HoFH的管理需要个性化的方法,考虑到功效,安全,每种治疗的耐受性和可及性。
OBJECTIVE: Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by markedly elevated circulating low-density lipoprotein cholesterol (LDL-C) from birth. This review aimed to critically evaluate treatments for HoFH with respect to their efficacy, safety, accessibility, overall context and position within the treatment pathway.
METHODS: A mixed-methods review was undertaken to systematically identify and characterize primary interventional studies on HoFH, with a focus on LDL-C reduction as the primary outcome. Interventions assessed were ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i),
lomitapide, evinacumab, with or without LDL apheresis.
RESULTS: Twenty-six seminal studies reporting unique patient data were identified. Four studies were randomized controlled trials (RCTs) with the remainder being single-arm trials or observational registries. Data extracted were heterogeneous and not suitable for meta-analyses. Two RCTs, assessed at being low risk of bias, demonstrated PCSK9i were safe and moderately effective. An RCT demonstrated evinacumab was safe and effective in all HoFH subgroups.
Lomitapide was reported to be efficacious in a single-arm trial, but issues with adverse events, tolerability, and adherence were identified. An RCT on ezetimibe showed it was moderately effective when combined with a statin. LDL apheresis was reported as effective, but its evidence base was at very high risk of bias. All interventions lowered LDL-C, but the magnitude of this, and certainty in the supporting evidence, varied.
CONCLUSIONS: In practice, multiple treatments are required to treat HoFH. The sequencing of these should be made on an individualized basis, with consideration made to the benefits of each intervention.
Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder that results in elevated cholesterol levels, which can cause premature cardiovascular events such as heart attacks and stroke. We performed a literature review to systematically identify and analyse studies reporting on newer treatments for HoFH which lower cholesterol levels, focussing on the overall advantages and disadvantages of each treatment. We identified 26 studies, including clinical trials and observational research, reporting on the interventions ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i),
lomitapide, evinacumab, and LDL apheresis. While all treatments showed promise in reducing cholesterol levels, none were sufficient to effectively treat HoFH on their own, and often the confidence in the results were limited by the methodological weaknesses of the studies. The evidence suggests that management of HoFH requires an individualized approach, with consideration given to the efficacy, safety, tolerability and accessibility of each treatment.