J Am Coll Cardiol. 2017 Oct 3;70(14):1785-1822. doi: 10.1016/j.jacc.2017.07.745. Epub 2017 Sep 5.
In 2016, the American College of Cardiology published the first expert consensus decision pathway (ECDP) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in the management of atherosclerotic cardiovascular disease (ASCVD) risk. Since the publication of that document, additional evidence and perspectives have emerged from randomized clinical trials and other sources, particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in secondary prevention of ASCVD. Most notably, the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial and SPIRE-1 and -2 (Studies of PCSK9 Inhibition and the Reduction of Vascular Events), assessing evolocumab and bococizumab, respectively, have published final results of cardiovascular outcomes trials in patients with clinical ASCVD and in a smaller number of high-risk primary prevention patients. In addition, further evidence on the types of patients most likely to benefit from the use of ezetimibe in addition to statin therapy after acute coronary syndrome has been published. Based on results from these important analyses, the ECDP writing committee judged that it would be desirable to provide a focused update to help guide clinicians more clearly on decision making regarding the use of ezetimibe and PCSK9 inhibitors in patients with clinical ASCVD with or without comorbidities. In the following summary table, changes from the 2016 ECDP to the 2017 ECDP Focused Update are highlighted, and a brief rationale is provided. The content of the full document has been changed accordingly, with more extensive and detailed guidance regarding decision making provided both in the text and in the updated algorithms. Revised recommendations are provided for patients with clinical ASCVD with or without comorbidities on statin therapy for secondary prevention. The ECDP writing committee judged that these new data did not warrant changes to the decision pathways and algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C <190 mg/dL with or without diabetes mellitus or patients without ASCVD and LDL-C ≥190 mg/dL not due to secondary causes. Based on feedback and further deliberation, the ECDP writing committee down-graded recommendations regarding bile acid sequestrant use, recommending bile acid sequestrants only as optional secondary agents for consideration in patients intolerant to ezetimibe. For clarification, the writing committee has also included new information on diagnostic categories of heterozygous and homozygous familial hypercholesterolemia, based on clinical criteria with and without genetic testing. Other changes to the original document were kept to a minimum to provide consistent guidance to clinicians, unless there was a compelling reason or new evidence, in which case justification is provided.
2016 年,美国心脏病学会发布了首个关于非他汀类药物降低低密度脂蛋白胆固醇在动脉粥样硬化性心血管疾病(ASCVD)管理中作用的专家共识决策路径(ECDP)。自该文件发布以来,随机临床试验和其他来源的更多证据和观点不断涌现,特别是考虑到前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9(PCSK9)抑制剂在 ASCVD 二级预防中的更长期疗效和安全性。值得注意的是,FOURIER(PCSK9 抑制剂在高危人群中的进一步心血管结局研究)试验和 SPIRE-1 和 -2(PCSK9 抑制剂抑制和血管事件减少研究),评估依洛尤单抗和 bococizumab,分别公布了 ASCVD 患者和少数高危一级预防患者心血管结局试验的最终结果。此外,还发表了关于在急性冠状动脉综合征后,除他汀类药物外,依折麦布对最有可能获益的患者类型的进一步证据。基于这些重要分析的结果,ECDP 写作委员会认为,有必要提供一个重点更新,以帮助临床医生更清楚地指导关于依折麦布和 PCSK9 抑制剂在有或无合并症的 ASCVD 患者中的使用决策。在下面的摘要表中,突出显示了 2016 年 ECDP 与 2017 年 ECDP 重点更新之间的变化,并提供了简要的基本原理。全文内容已相应更改,在文本和更新的算法中提供了更广泛和详细的决策指导。为他汀类药物二级预防中有或无合并症的 ASCVD 患者提供了修订后的推荐意见。ECDP 写作委员会认为,这些新数据并不需要更改关于在 LDL-C<190mg/dL 且无糖尿病或无 ASCVD 且 LDL-C≥190mg/dL 且非继发原因的患者中使用依折麦布或 PCSK9 抑制剂的一级预防患者中使用依折麦布或 PCSK9 抑制剂的决策路径和算法。基于反馈和进一步的审议,ECDP 写作委员会降低了关于胆汁酸螯合剂使用的建议,仅建议将胆汁酸螯合剂作为不耐受依折麦布的患者的可选二级药物。为了澄清起见,写作委员会还根据有或无基因检测的临床标准,包括新的杂合子和纯合子家族性高胆固醇血症的诊断类别信息。除非有令人信服的理由或新证据,否则对原始文件的其他更改保持在最低限度,以便为临床医生提供一致的指导,在这种情况下,提供了理由。
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