Low-density lipoprotein-cholesterol (LDL-C) is a well-accepted causal risk factor for athero-thrombotic cardiovascular disease, as demonstrated in large epidemiological studies, including Mendelian randomization data. Several randomized controlled trials and meta-analyzes have shown that lipid lowering therapies, such as statins and more recently the non-statin agents ezetimibe and Proprotein Convertase Subtilisin Kexin type 9 (PCSK9) monoclonal antibodies (mAb), reduce cardiovascular events across a broad range of baseline LDL-C levels. Over time, the recommended target for LDL-C has become more stringent, moving from 2.6 mmol/l to 1.8 mmol/l in very high-risk patients. It is currently recommended to start high intensity statin treatment immediately after acute coronary syndromes (ACS) to maximally and rapidly reduce LDL-C. The novel treatment options enable the achievement of very low LDL-C levels below 1 mmol/l, with no reported safety issues, in particular with regard to neurocognitive events. However, current evidence supports the use of PCSK9 mAb treatment in ACS patients only after an initial 2-3 month run-up treatment adaptation period with maximally tolerated statin. The use of PCSK9 mAb immediately in the acute phase of ACS (<1 month) remains to be studied. Some data suggest that circulating PCSK9 increases coronary plaque vulnerability, inflammation as well as platelet aggregation in the acute phase of ACS, potentially justifying earlier PSCK9 mAb treatment initiation. As the use of novel treatment combinations in ACS is further explored to widen the perspectives of a more personalized approach for the management of ACS based on individual patient risk profile and baseline LDL-C values, their relative cost-effectiveness will also need to be assessed.

译文

低密度脂蛋白胆固醇 (ldl-c) 是动脉粥样硬化血栓性心血管疾病的公认因果危险因素,包括孟德尔随机化数据在内的大型流行病学研究证明。一些随机对照试验和荟萃分析表明,降脂疗法,例如他汀类药物和最近的非他汀类药物依折麦贝和前蛋白转化酶枯草杆菌蛋白酶Kexin 9型单克隆抗体 (mAb),可减少心血管事件广泛的基线ldl-c水平。随着时间的推移,ldl-c的推荐目标变得更加严格,在高危患者中从2.6  mmol/l变为1.8  mmol/l。目前建议在急性冠状动脉综合征 (ACS) 后立即开始高强度他汀类药物治疗,以最大程度地快速降低ldl-c。新的治疗方案使ldl-c水平低于1 mmol mmol/l,没有安全性问题的报道,特别是关于神经认知事件。然而,目前的证据支持在ACS患者中使用PCSK9 mAb治疗仅在初始2-3个月的启动治疗适应期后使用最大耐受他汀类药物。在ACS急性期 (<1个月) 立即使用PCSK9 mAb仍有待研究。一些数据表明,在ACS急性期,循环PCSK9会增加冠状动脉斑块的脆弱性,炎症以及血小板聚集,这可能证明较早开始PSCK9 mAb治疗是合理的。随着在ACS中使用新型治疗组合的进一步探索,以扩大基于个体患者风险状况和基线ldl-c值的更加个性化的ACS管理方法的观点,还需要评估其相对成本效益。

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