利用腔内影像观察他汀联用PCSK9抑制剂对冠状动脉粥样斑块影响的Meta分析

Effect of statins combined with PCSK9 inhibitors on coronary atheromatous plaque assessed by intravascular imaging:a Meta-analysis

目的评估他汀联用PCSK9抑制剂(PCSK9i)的降脂治疗对冠状动脉粥样斑块的作用,并验证他汀联用PCSK9i的降脂效果。方法通过检索PubMed、Embase、Web of Science、Cochrane图书馆、万方、知网数据库,获取从建库到2022年12月20日的全部文献。英文检索关键词为“PCSK9 Inhibitors”“Alirocumab”“Evolocumab”“plaque”“IVUS”“OCT”等,中文检索关键词为“PCSK9抑制剂”“斑块”“血管内超声”“光学相干断层扫描”等。筛选所有利用血管内超声(IVUS)或光学相干断层扫描(OCT)观察他汀治疗与他汀联用PCSK9i治疗后冠状动脉粥样斑块的文献。使用Review Manager(Revman)5.4处理数据。结果共纳入9项研究,1912例患者。分析结果显示,相较于他汀单药治疗,他汀联用PCSK9i能够显著改善动脉粥样硬化百分比(PAV)(MD:-2.08 mm^(3),95%CI:-2.94~-1.23 mm^(3),P<0.001),加速PAV的消退(MD:-1.13 mm^(3),95%CI:-1.49~-0.77 mm^(3),P<0.001);改善总动脉粥样硬化体积(TAV)(MD:-6.42 mm^(3),95%CI:-14.34~1.51 mm^(3),P=0.110),但差异无统计学意义;促进TAV消退(MD:-5.16 mm^(3),95%CI:-7.09~-3.23 mm^(3),P<0.001);显著增加薄帽斑块纤维帽厚度(FCT)(MD:8.46μm,95%CI:5.13~11.79μm,P<0.001)。此外,他汀联合PCSK9i治疗可以明显降低患者血脂水平。结论他汀联用PCSK9i可明显改善粥样斑块的特征和表型,并大幅降低血脂水平。对于存在高心血管风险的患者,建议尽早启动他汀联合PCSK9i治疗,并长期维持,确保更多获益。

Objective To evaluate the effect of statins combined with PCSK9 inhibitors on coronary artery atherosclerotic plaque,as well as to verify the lipid-lowering effect of the combined therapy.Methods A computerized search of PubMed,Embase,Web of Science,Cochrane Library,Wanfang,and CNKI databases was conducted to retrieve published literature from inception to December 20,2022.The English search terms utilized included"PCSK9 inhibitors,""Alirocumab,""Evolocumab,""plaque,""IVUS,"and"OCT."The corresponding Chinese search terms were"PCSK9 inhibitors,""plateau,""intravascular ultrasound,"and"optical coherence tomography."The literature that examined the effect of statins alone or in combination with PCSK9 inhibitors on coronary atherosclerotic plaques using intravascular ultrasound or optical coherence tomography was identified.The collected data were subsequently processed using Review Manager(Revman)version 5.4.Results In the final analysis,nine studies involving 1912 patients were included.The analysis results revealed that compared with statins alone,statins combined with PCSK9 inhibitors significantly reduced the percentage of atherosclerotic volume(MD:-2.08 mm^(3),95%CI:-2.94 to-1.23 mm^(3),P<0.001),accelerated the regression of atherosclerotic volume(MD:-1.13 mm^(3),95%CI:-1.49 to-0.77 mm^(3),P<0.001),slightly,but not significantly,reduced the overall atherosclerotic volume(MD:-6.42 mm^(3),95%CI:-14.34-1.51 mm^(3),P=0.110).Nevertheless,the combined therapy contributed to a significant reduction in atherosclerotic volume(MD:-5.16 mm^(3),95%CI:-7.09 to-3.23 mm^(3),P<0.001)and significantly increased the fiber cap thickness of thin cap plaques(MD:8.46μm,95%CI:5.13-11.79μm,P<0.001).Additionally,this combined therapy significantly lowered blood lipid levels.Conclusion The combination of statins and PCSK9 inhibitors can significantly improve the characteristics and phenotype of atherosclerotic plaques and significantly reduce blood lipid levels.For patients with high cardiovascular risk,it is recommended to initiate treatment with statins combined with PCSK9 inhibitors as soon as possible and maintain it for a long time to ensure more benefits.