PCSK9抑制剂临床应用安全性评价

Safety evaluation of PCSK9 inhibitors in clinical application

降低低密度脂蛋白-胆固醇(LDL-C)是动脉粥样硬化性心血管疾病(ASCVD)防治的核心策略。目前,他汀类药物是降低LDL-C的首选药物,显著降低ASCVD患者的发病率和死亡率。然而,临床研究及实践表明,即使强化他汀治疗,仍有相当数量的患者LDL-C水平不达标,且部分患者出现他汀不耐受及相关不良反应,因此,研究者在不断探索新的降低LDL-C安全、有效的药物。近年大型临床试验表明,人前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂单独应用或联合他汀类药物和或其他降脂药物均可显著降低LDL-C至极低水平,并进一步带来心血管获益。本文着重分析PCSK9抑制剂、极低水平LDL-C的安全性问题,为临床正确使用PCSK9抑制剂提供参考。

Reduction of low density lipoprotein-cholesterol(LDL-C)level is the cornerstone in the treatment and prevention of atherosclerotic cardiovascular disease(ASCVD).At present,as the first choice for LDL-C lowering,high-intensity statins has been demonstrated to significantly decrease the morbidity and mortality of ASCVD patients.However,there are still some patients who cannot be tolerable or have poor response or compliance to statins.Therefore,the combination of statins and other therapies should be considered,and recently,major clinical trials have shown that proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors with or without statins and/or other lipid-lowering therapies in patients can significantly reduce LDL-C levels,even to the lowest level ever,which brings about cardiovascular benefits.This review focuses on the overall safety issues of PCSK9 inhibitors and very low-level LDL-C,in order to provide references for the appropriate clinical appropriate application of this new lipid-lowering drug.