前蛋白转化酶枯草溶菌素9（PCSK9）单克隆抗体（依洛尤单抗）联合瑞舒伐他汀和依折麦布对冠心病（CHD）患者胆固醇水平的疗效评估：来自中国某单中心的回顾性分析

Efficacy evaluation of PCSK9 monoclonal antibody (Evolocumab) in combination with Rosuvastatin and Ezetimibe on cholesterol levels in patients with coronary heart disease (CHD): A retrospective analysis from a single center in China.

作者信息

Liu Yi, Han Bing

机构信息

MM, Cardiac Diagnosis and Treatment Center, Xuzhou Central Hospital, Xuzhou City, Jiangsu Province, China.

出版信息

Transpl Immunol. 2022 Apr;71:101444. doi: 10.1016/j.trim.2021.101444. Epub 2021 Aug 8.

DOI:10.1016/j.trim.2021.101444

PMID:34375677

Abstract

BACKGROUND AND PURPOSE

Proprotein convertase subtilisin-kexin type 9(PCSK9) monoclonal antibody (Mab; Evolocumab) has been reported to inhibit low-density lipoprotein cholesterol (LDL-C) and Lipoprotein(a) [LP(a)] in coronary heart diseases (CHD) patients in America, Europe and Japan. However, little is known about the effect of Evolocumab in Chinese population. This retrospective study in Chinese CHD patients compared the efficacy without or with Evolocumab therapy added to the conventional treatment with a statin (Rosuvastatin) and a gut cholesterol absorption inhibitor (Ezetimibe).

METHODS

CHD patients from our hospital were divided into three therapeutic groups, A) the statin monotherapy group (10 mg Rosuvastatin every night); B) the statin/cholesterol absorption inhibitor group (10 mg Rosuvastatin and 10 mg Ezetimibe daily); and C) the triple therapy with PCSK9 Mab group (10 mg Rosuvastatin daily, 10 mg Ezetimibe daily, and 140 mg Evolocumab once 2 weeks). The plasma lipid data were collected at 0, 4, 12, and 24 Week(s). The Graphpad Prism 7 program was used to perform all the statistical analysis.

RESULTS

Out of 103 patients 91 were eligible for further evaluation with 31 in group A, 31 in group B, and 29 in group C. The plasma LDL-C levels were reduced only by 33.82% in the Rosuvastatin monotherapy group, 52.13% in the Rosuvastatin/Ezetimibe group, and 73.59% in the Evolocumab/Rosuvastatin/Ezetimibe group (P < 0.0001) at 24 weeks compared to the prior therapy levels. Neither the statin therapy alone (5.95%; P = 0.6), nor the double therapy (5.27%; P = 0.7) affected LP(a) levels. In contrast, addition of Evolocumab to the double therapy significantly decreased LP(a) level by 37.2% (P < 0.0001).

CONCLUSION

Addition of Evolocumab to the standard double therapy in Chinese CHD patients improved the efficacy in LDL-C reduction when compared to Rosuvastatin alone or in Rosuvastatin/Ezetimibe double therapy. Furthermore, the addition of Evolocumab lowered LP(a) level in Chinese CHD patients.

摘要

背景与目的

据报道，前蛋白转化酶枯草溶菌素9型（PCSK9）单克隆抗体（Mab；阿利西尤单抗）可降低美国、欧洲和日本冠心病（CHD）患者的低密度脂蛋白胆固醇（LDL-C）和脂蛋白(a)[LP(a)]水平。然而，阿利西尤单抗在中国人群中的效果尚不清楚。这项针对中国冠心病患者的回顾性研究比较了在常规治疗（使用他汀类药物瑞舒伐他汀和肠道胆固醇吸收抑制剂依折麦布）基础上加用或不加用阿利西尤单抗治疗的疗效。

方法

将我院的冠心病患者分为三个治疗组，A）他汀类药物单药治疗组（每晚服用10mg瑞舒伐他汀）；B）他汀类药物/胆固醇吸收抑制剂组（每日服用10mg瑞舒伐他汀和10mg依折麦布）；C）PCSK9 Mab三联治疗组（每日服用10mg瑞舒伐他汀，每日服用10mg依折麦布，每2周注射140mg阿利西尤单抗）。在第0、4、12和24周收集血脂数据。使用Graphpad Prism 7软件进行所有统计分析。

结果

103例患者中，91例符合进一步评估标准，其中A组31例，B组31例，C组29例。与治疗前水平相比，24周时瑞舒伐他汀单药治疗组的血浆LDL-C水平仅降低了33.82%，瑞舒伐他汀/依折麦布组降低了52.13%，阿利西尤单抗/瑞舒伐他汀/依折麦布组降低了73.59%（P<0.0001）。单独使用他汀类药物治疗（5.95%；P=0.6）和双联治疗（5.27%；P=0.7）均未影响LP(a)水平。相比之下，在双联治疗基础上加用阿利西尤单抗可使LP(a)水平显著降低37.2%（P<0.0001）。