低密度脂蛋白胆固醇(LDL-C)升高是动脉粥样硬化性心血管疾病(ASCVD)的主要病因,全球死亡的主要原因。他汀类药物是原发性高胆固醇血症和已确诊的ASCVD患者推荐的一线降脂治疗(LLT)。在单用他汀类药物治疗未达到低于指南推荐的LDL-C阈值的患者中,有相当大比例的患者推荐LLT强化。前蛋白转化酶枯草杆菌蛋白酶/kexin9型抑制剂单克隆抗体evolocumab在临床试验和开放标签延伸设置中已证明LDL-C显着降低>60%,在evolocumab开始后早期观察到LDL-C降低并长期维持,在长达8.4年的随访中。Evolocumab治疗,当添加到他汀类药物中时,还显著减少了主要心血管(CV)事件,包括将CV死亡的复合物减少20%,心肌梗死(MI),或中风。在继发性ASCVD高风险和极高风险的各种患者类型中,绝对益处得到了增强(例如,最近的MI,多个事件或外周动脉疾病)。重要的是,在延长的随访期间,evolocumab治疗导致CV风险降低,包括CV死亡率降低23%,LDL-C水平无明显变化,低于LDL-C水平则不会进一步降低CV风险.因此,evolocumab临床数据支持早期和显著降低LDL-C的需要,尤其是在脆弱的ASCVD患者中,以便从长远来看获得最大的利益。重要的是,除了局部注射部位反应少量增加外,evolocumab对任何治疗引起的不良事件均无影响.越来越多的真实世界证据(RWE)在异质人群中的evolocumab与试验数据是一致的,包括稳健的LDL-C降低低于指南建议的阈值,即使在LDL-C达到的最低水平,也具有良好的安全性,和>90%的高治疗持续率。总之,这篇综述强调了50项临床试验和RWE研究的结果,这些研究涉及>51,000名接受evolocumab治疗的患者,证明evolocumab在各种高危和极高危患者中解决LDL-C降低和ASCVD二级预防方面的医疗保健差距的潜力。
Elevated low-density lipoprotein cholesterol (LDL-C) is a major causal factor for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality worldwide. Statins are the recommended first-line lipid-lowering therapy (LLT) for patients with primary hypercholesterolemia and established ASCVD, with LLT intensification recommended in the substantial proportion of patients who do not achieve levels below guideline-recommended LDL-C thresholds with statin treatment alone. The proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody evolocumab has demonstrated significant LDL-C reductions of > 60% in the clinical trial and open-label extension settings, with LDL-C reductions observed early post-evolocumab initiation and maintained long term, during up to 8.4 years of follow-up. Evolocumab therapy, when added to a statin, also conferred a significant reduction in major cardiovascular (CV) events, including a 20% reduction in the composite of CV death, myocardial infarction (MI), or stroke. The absolute benefits were enhanced among various patient types at high and very high risk for secondary ASCVD (e.g., with recent MI, multiple events or peripheral artery disease). Importantly, evolocumab treatment resulted in incremental CV risk reductions during the extended follow-up, including a 23% reduction in CV mortality and no apparent LDL-C level below which there is no further CV risk reduction. Hence, the evolocumab clinical data support the need for early and significant LDL-C lowering, especially in vulnerable ASCVD patients, in order to derive the greatest benefit in the long term. Importantly, evolocumab had no impact on any treatment emergent adverse events apart from a small increase in local injection site reactions. A growing body of real-world evidence (RWE) for evolocumab in heterogeneous populations is consistent with the trial data, including robust LDL-C reductions below guideline-recommended thresholds, a favourable safety profile even at the lowest levels of LDL-C achieved, and a high treatment persistence rate of > 90%. Altogether, this review highlights findings from 50 clinical trials and RWE studies in > 51,000 patients treated with evolocumab, to demonstrate the potential of evolocumab to address the healthcare gap in LDL-C reduction and secondary prevention of ASCVD in a variety of high- and very high-risk patients.