Liu Sen, Wang Peijian, Liu Cheng, Jin Menglong, Wan Jindong, Hou Jixin, Yang Yi, Wang Dan, Liu Ziyang, Fu Zhenyan
Heart Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China; Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu 610500, Sichuan, China; Sichuan Clinical Research Center for Geriatrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan, China; Key Laboratory of Aging and Vascular Homeostasis of Sichuan Higher Education Institutes, Chengdu 610500, Sichuan, China.
Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu 610500, Sichuan, China; Sichuan Clinical Research Center for Geriatrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan, China; Key Laboratory of Aging and Vascular Homeostasis of Sichuan Higher Education Institutes, Chengdu 610500, Sichuan, China.
Int J Cardiol. 2023 Dec 1;392:131330. doi: 10.1016/j.ijcard.2023.131330. Epub 2023 Sep 4.
Despite extensive evidence demonstrating the beneficial effects of the additional PCSK9 antibodies with high-density statins treatment on cardiovascular clinical outcomes, the potent causes underlying these effects remain elusive. This meta-analysis aimed at exploring the underlying causes to assess the effect of PCSK9 antibodies on the regression and stabilization of coronary plaque derived from intravascular imaging in statin-treated patients with coronary artery disease (CAD).
PubMed, Embase, and Cochrane Library were searched from inception to February 1, 2023, for randomized controlled trials (RCTs), nonrandomized studies without language restrictions if they described the association between PCSK9 antibodies with coronary plaque regression and stabilization evaluated by intravascular imaging in statin-treated patients with CAD. Meta-analyses were performed for mean difference (MD) and odds ratio (OR) using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
A total of 9 studies (7 RCTs and 2 non-RCTs) with 2290 CAD patients were identified and included. Among statin-treated CAD patients, the addition use of PCSK9 antibodies was associated with IVUS-derived percent atheroma volume (PAV) (4 studies with 1875 participants; MD, -1.26; 95% CI, -1.51 to -1.00; P < 0.01), total atheroma volume (TAV) (4 studies with 1875 participants; MD, -7.23; 95% CI, -11.28 to -3.18; P < 0.01), incidence of PAV regression (4 studies with 1875 participants; OR, 2.24; 95% CI, 1.81 to 2.77; P < 0.01) and incidence of TAV regression (3 studies with 1256 participants; OR, 1.66; 95% CI, 1.33 to 2.09; P < 0.01) in Caucasians instead of Asians from multiple countries; OCT-derived minimum fibrous cap thickness (FCT) (6 studies with 841 participants; MD, 25.16; 95% CI, 14.06 to 36.27; P < 0.01), incidence of thin-capped fibroatheroma (TCFA) regression (2 studies with 222 participants; OR, 2.56; 95% CI, 1.42 to 4.61; P < 0.01) and maximum lipid arc (4 studies with 280 participants; MD, -14.96; 95% CI, -22.10 to -7.83; P < 0.01) in Asians and Caucasians without races restrictions.
PCSK9 antibodies resulted in significantly greater coronary plaque regression and stabilization in statin-treated CAD patients, mostly Caucasians from multiple countries. Further studies are needed to assess the effect for Asian patients.
尽管有大量证据表明，在使用高强度他汀类药物治疗的基础上额外使用前蛋白转化酶枯草溶菌素9（PCSK9）抗体对心血管临床结局具有有益作用，但其潜在的有效原因仍不明确。本荟萃分析旨在探究潜在原因，以评估PCSK9抗体对接受他汀类药物治疗的冠心病（CAD）患者血管内成像显示的冠状动脉斑块消退和稳定的影响。
检索了PubMed、Embase和Cochrane图书馆，检索时间从建库至2023年2月1日，纳入随机对照试验（RCT）、非随机研究，无语言限制，只要其描述了PCSK9抗体与接受他汀类药物治疗的CAD患者血管内成像评估的冠状动脉斑块消退和稳定之间的关联。采用随机效应模型对均数差（MD）和比值比（OR）进行荟萃分析。本研究遵循系统评价和荟萃分析的首选报告项目（PRISMA）报告指南。
共纳入9项研究（7项RCT和2项非RCT），涉及2290例CAD患者。在接受他汀类药物治疗的CAD患者中，额外使用PCSK9抗体与血管内超声（IVUS）得出的粥样硬化斑块体积百分比（PAV）相关（4项研究，1875名参与者；MD，-1.26；95%CI，-1.51至-1.00；P<0.01）、总粥样硬化斑块体积（TAV）（4项研究，1875名参与者；MD，-7.23；95%CI，-11.28至-3.18；P<0.01）、PAV消退发生率（4项研究，1875名参与者；OR，2.24；95%CI，1.81至2.77；P<0.01）以及TAV消退发生率（3项研究，1256名参与者；OR，1.66；95%CI，1.33至2.09；P<0.01），这些结果来自多个国家的白种人而非亚洲人；光学相干断层扫描（OCT）得出的最小纤维帽厚度（FCT）（6项研究，841名参与者；MD，25.16；95%CI，14.06至36.27；P<0.01）、薄帽纤维粥样斑块（TCFA）消退发生率（2项研究，222名参与者；OR，2.56；95%CI，1.42至4.61；P<0.01）以及最大脂质弧（4项研究，280名参与者；MD，-14.96；95%CI，-22.10至-7.83；P<0.01），这些结果来自无种族限制的亚洲人和白种人。
PCSK9抗体可使接受他汀类药物治疗的CAD患者，主要是来自多个国家的白种人，冠状动脉斑块出现显著更大程度的消退和稳定。需要进一步研究评估其对亚洲患者的影响。
