通过OCT评估冠脉临界病变患者使用PCSK9 抑制剂的疗效及安全性

Evaluating the Efficacy and Safety of PCSK9 Inhibitors in Patients with Coronary Intermediate Borderline Lesions Using Optical Coherence Tomography (OCT)

摘要: 目的：运用OCT技术观察依洛尤单抗联合中等剂量他汀治疗冠状动脉临界病变患者的疗效及不良反应情况，为此类患者探索新的内科保守干预策略。方法：选取2024年3月至2025年3月就诊于内蒙古自治区人民医院心血管内科，经冠状动脉造影确诊为冠脉临界病变(直径狭窄率50%~70%)的患者作为研究对象，将所有患者分成观察组和对照组，均接受常规冠心病治疗(不包含降脂药物)，观察组接受依洛尤单抗联合中等强度他汀治疗，对照组则仅采用中等强度他汀进行治疗。整理每个患者的性别、年龄、BMI、吸烟饮酒史、糖尿病病史、高血压病史，并对治疗前的FCT、最大脂质弧、MLA、MLD进行测量，同时记录LDL-C、Lp(a)、TG、TC、HDL-C、Scr、FBG、ALT、AST、UA等生化指标。经过12个月治疗后，再次行OCT检查，以观察FCT、最大脂质弧、MLA、MLD的变化。分别在研究对象入组后的第1、3、6、9、12个月，对其进行LDL-C、Lp(a)、TG、TC、HDL-C、Scr、FBG、ALT、AST、UA等生化指标测量，通过面对面交流及电话回访，记录患者是否出现肝酶升高、肌酐异常、新发糖尿病及肌肉疼痛等不良反应。此外，还会记录胸痛发作、心力衰竭及心源性死亡等主要心血管事件，以评估在冠状动脉临界病变患者中使用依洛尤单抗联合中等强度他汀的疗效和安全性。使用SPSS 26.0进行数据分析，P < 0.05时差异具有统计学意义。结果：本次研究共招募了62名参与者，经研究得出以下结果：(1) 在治疗前，观察组与对照组的基线资料、生化指标及FCT、最大脂质弧、MLA、MLD水平均无统计学差异(P > 0.05)。(2) 在每个时间段中，观察组的降脂效果比对照组更为突出，两组之间差异具有统计学意义(P < 0.05)。(3) 观察组FCT、最大脂质弧、MLA、MLD水平的变化均优于对照组，并且两组之间差异具有统计学意义(P < 0.05)。(4) 在不良反应和心血管问题方面，观察组报告3例反复胸痛，占比10%；对照组则有12例，占比37.5%，两组数据相比存在显著差异(P < 0.05)。两组给药方案在肝功能指标升高、血肌酐异常、新发糖尿病及肌肉疼痛等不良反应方面的差异未达到统计学显著水平。结论：(1) 相比于传统降脂治疗，结合依洛尤单抗的治疗能够更有效地降低LDL-C、TC、TG及Lp(a)水平，有助于更快实现血脂达标。(2) 与传统治疗相比，依洛尤单抗与他汀类药物联合应用能增加纤维帽的厚度，让相当一部分患者免于易损斑块的风险，明显减少斑块破裂的可能性。(3) MLA和MLD的改善表明斑块负荷减轻和管腔良性正向重构。这一效应不仅可改善心肌供血，还可能为未来避免或延迟血运重建提供机会。(4) 通过分析研究中出现的不良反应及心血管事件，能够确认依洛尤单抗与他汀类药物联合使用的安全性。

Abstract: Objective: To observe the efficacy and adverse reactions of evolocumab combined with moderate-intensity statin therapy in patients with borderline coronary artery lesions using OCT technology, and to explore new conservative medical intervention strategies for such patients. Methods: Patients diagnosed with borderline coronary artery lesions (diameter stenosis rate 50%~70%) by coronary angiography at the Cardiology Department, People’s Hospital of Inner Mongolia Autonomous Region, from March 2024 to March 2025, were selected as study subjects. All patients were divided into an observation group and a control group, both receiving conventional coronary heart disease treatment (excluding lipid-lowering drugs). The observation group received evolocumab combined with moderate-intensity statin therapy, while the control group received moderate-intensity statin therapy alone. Data collected included gender, age, BMI, smoking and drinking history, history of diabetes, and history of hypertension for each patient. Pre-treatment measurements included Fibrous Cap Thickness (FCT), maximum lipid arc, Minimal Lumen Area (MLA), and Minimal Lumen Diameter (MLD), as well as biochemical indicators such as LDL-C, Lp(a), TG, TC, HDL-C, Scr, FBG, ALT, AST, and UA. After 12 months of treatment, OCT was repeated to observe changes in FCT, maximum lipid arc, MLA, and MLD. Biochemical indicators such as LDL-C, Lp(a), TG, TC, HDL-C, Scr, FBG, ALT, AST, and UA were measured at 1, 3, 6, 9, and 12 months after enrollment. Adverse reactions such as elevated liver enzymes, abnormal serum creatinine, new-onset diabetes, and muscle pain were recorded through face-to-face interviews and telephone follow-ups. Major cardiovascular events, including chest pain episodes, heart failure, and cardiac death, were also recorded to evaluate the efficacy and safety of evolocumab plus moderate-intensity statin in patients with borderline coronary artery lesions. SPSS 26.0 was used for data analysis, with statistical significance set at P < 0.05. Results: A total of 62 participants were initially recruited, and the following results were obtained: (1) No significant differences were found between the two groups in baseline characteristics, biochemical indicators, or FCT, maximum lipid arc, MLA, and MLD levels before treatment (P > 0.05). (2) At each time point, the lipid-lowering effect in the observation group was significantly better than that in the control group, showing a significant difference (P < 0.05). (3) Changes in FCT, maximum lipid arc, MLA, and MLD were significantly better in the observation group than in the control group, showing a significant difference (P < 0.05). (4) Regarding adverse reactions and cardiovascular events, the observation group reported 3 cases of recurrent chest pain (10%), while the control group reported 12 cases (37.5%), showing a significant difference (P < 0.05). No statistically significant differences were observed between the two groups in terms of elevated liver enzymes, abnormal serum creatinine, new-onset diabetes, or muscle pain. Conclusions: (1) Compared with traditional lipid-lowering therapy, evolocumab combined with statin therapy more effectively reduces LDL-C, TC, TG, and Lp(a) levels, helping to achieve lipid targets more rapidly. (2) The combination of evolocumab and statins increases fibrous cap thickness compared with traditional therapy, sparing a considerable number of patients from vulnerable plaque risk and significantly reducing the likelihood of plaque rupture. (3) Improvements in MLA and MLD indicate reduced plaque burden and favorable positive vessel remodeling. This effect not only improves myocardial blood supply but may also provide an opportunity to avoid or delay revascularization. (4) Analysis of adverse reactions and cardiovascular events in the study confirms the safety of evolocumab combined with statin therapy.