【作者】 刘洋；

【导师】 谷新顺；

【作者基本信息】 河北医科大学 ， 内科学（专业学位）， 2023， 硕士

【摘要】 目的:探讨急性ST段抬高型心肌梗死患者应用阿利西尤单抗的临床疗效及药物安全性方法:本研究为单中心、前瞻性研究。收集整理2021年10月至2022年4月就诊于河北医科大学第二医院心血管内五科,符合急性ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)诊断标准的患者86例的临床资料,依据其降脂治疗方案分为他汀类联合阿利西尤单抗强化治疗的试验组(n=37)和单用中等强度剂量他汀类治疗的对照组(n=49)。记录分析入选患者的年龄、性别、BMI、高血压病史、糖尿病病史、吸烟史、心血管基础药物使用情况及常规生化指标等基线资料。统计整理两组患者用药半个月、1个月、3个月、半年后的血脂水平变化、主要不良心血管事件发生情况、药物不良反应发生及部分患者的炎症指标变化情况等资料。所有数据通过SPSS 26.0统计软件进行分析,P<0.05认为其差异具有统计学意义。结果:1.入选的两组患者在年龄、性别、体重指数、高血压、糖尿病、吸烟情况、他汀类、依折麦布、抗血小板药、β受体阻滞剂、ACEI/ARB、白细胞计数、谷丙转氨酶、血肌酐、射血分数、CK-MB峰值、前壁心梗等方面差异均无统计学意义。(P>0.05);2.两组患者在开始应用不同降脂治疗方案前,其基础的总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白B(Apo B)、脂蛋白[Lp(a)]等指标方面差异均无统计学意义(P>0.05);3.半个月时两组组间血脂结果对比显示,与对照组相比,试验组相关血脂指标TC、LDL-C、HDL-C、Apo B、Lp(a)均有明显降低或改善,差异有统计学意义(P<0.05)。而两组患者TG的水平均较入院时基线水平有所下降,但两组组间无统计学差异。1个月时,试验组与对照组患者的相关血脂指标水平TC、TG、LDL-C、Apo B、Lp(a)与入院时的基线水平、半个月时的对应指标水平相比均降低,组间差异有统计学意义(P<0.05)。HDL-C水平相较入院时、半个月时升高,组间差异有统计学意义(P<0.05)。3个月时,将试验组与对照组的血脂指标水平进行组间比较,TC、LDL-C、Apo B、Lp(a)、HDL-C与入院时等前述时间节点水平相比,均有显著的降低或升高,有统计学差异(P<0.05)。用药3个月后TG水平虽较之前仍有下降趋势,但两组组间无统计学差异。半年时,两组患者其TC、LDL-C、Apo B、L p(a)水平较前均有所降低,HDL-C水平较前有所升高,组间差异有统计学意义。TG水平虽较前相比有所降低,但两组组间差异无统计学意义(P>0.05)。分别对两组各个时间点的LDL-C水平进行重复测量设计的方差分析结果显示,试验组LDL-C水平随时间延长呈进行性下降,不同时间点之间的LDL-C值差异具有统计学意义(P<0.05)。4.随访期间内试验组不良心血管事件发生率为8.1%。其中1位患者因心力衰竭住院、1位患者因不稳定型心绞痛反复住院患者、1位患者因行冠脉血运重建住院;而对照组MACE发生率为22.4%。其中有1例患者为心血管死亡患者,再发心肌梗死患者1例、2例患者因心力衰竭住院、4例患者因不稳定型心绞痛住院、3例患者行冠脉血运重建。两组患者各单一心血管事件差异无统计学意义(P>0.05),但对照组与试验组患者的复合不良心血管事件发生率存在差异(P<0.05),其中试验组主要不良心血管事件发生率显著低于对照组。5.药物不良反应:随访记录期间,试验组有1例患者出现注射部位不适症状,后自行缓解,1例患者出现胃肠道反应;对照组有2例患者出现肌肉疼痛情况,2例患者出现肝功能异常情况。余患者未诉特殊药物不良反应症状。两组患者不良反应方面无统计学差异(P>0.05)。6.两组组间炎症指标结果对比显示,与对照组相比,试验组相关炎症指标水平(IL-1β、TNF-α)均有明显的降低,各个时间节点组间差异有统计学意义(IL-1β:基线时37.1±4.6pg/ml～36.8±5.3 pg/ml,3个月时8.2±1.5pg/ml～16.3±1.8pg/ml,半年时7.5±0.9pg/ml～16.1±0.6pg/ml,P<0.05;TNF-α:基线时44.7±3.4 pg/ml～46.2±2.4 pg/ml,3个月时15.1±3.5 pg/ml～23.5±5.2 pg/ml,半年时10.5±2.3 pg/ml～20.8±2.6 pg/ml,P<0.05)。而各时间节点结果对比,炎症指标中的hs-CRP,其组间差异均无统计学意义(P>0.05)。结论:对于急性ST段抬高型心肌梗死患者来说,在他汀类药物降脂治疗基础上联用阿利西尤单抗强化治疗,不仅显著降低相关血脂指标水平,还有降低MACE的趋势,同时在炎症指标方面也有降低趋势,且临床安全性、耐受性良好。更多还原

【Abstract】 Objective: To investigate the clinical efficacy and safety of alirocumab in patients with acute ST-segment elevation myocardial infarction.Methods:This study was a single-center,prospective and registered study.The clinical data of 86 patients who met the diagnostic criteria of acute ST-segment elevation myocardial infarction(STEMI)in the fifth Department of Cardiology,the Second Hospital of Hebei Medical University from October2021 to April 2022 were collected.According to their lipid-lowering treatment regimen,they were divided into the experimental group(n=37)with intensive treatment of statins combined with alirocumab and the control group(n=49)with moderate intensity dose of statins alone.The baseline data of age,gender,BMI,history of hypertension,history of diabetes,smoking history,use of cardiovascular basic drugs,and routine biochemical indicators were recorded and analyzed.The changes of blood lipid levels,the occurrence of major adverse cardiovascular events,adverse drug reactions and the changes of inflammatory indicators in some patients of the two groups were statistically analyzed after half a month,1 month,3 months and half a year of medication.All data were analyzed by SPSS 26.0 statistical software,and P<0.05 was considered statistically significant.Results:1.There were no significant differences in age,gender,body mass index,hypertension,diabetes,smoking,statins,ezetimibe,antiplatelet drugs,β-blockers,ACEI/ARB,white blood cell count,alanine aminotransferase,serum creatinine,ejection fraction,CK-MB peak value,anterior myocardial infarction between the two groups.(P>0.05);2.Before the initiation of different lipid-lowering therapies,There were no significant differences in baseline total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),apolipoprotein B(Apo B),lipoprotein [Lp(a)] and other indicators(P>0.05).3.The comparison of blood lipid results between the two groups showed that compared with the control group,the related blood lipid indicators TC,LDL-C,HDL-C,Apo B,Lp(a)in the experimental group were significantly reduced or improved,the difference was statistically significant(P<0.05).However,the TG levels of the two groups were lower than the baseline level on admission,but there was no significant difference between the two groups.At 1 month,the levels of TC,TG,LDL-C,Apo B,and Lp(a)in the experimental group and the control group were lower than the baseline levels on admission and the corresponding index levels at half month,and the differences between the two groups were statistically significant(P<0.05).The HDL-C level was higher than that at admission and half a month after admission,and the difference between the two groups was statistically significant(P<0.05).At 3 months,the levels of TC,LDL-C,Apo B,Lp(a),and HDL-C in the experimental group and the control group were significantly lower or higher than those at the above-mentioned time points on admission,with statistically significant differences(P<0.05).After 3 months of treatment,the TG level still showed a downward trend,but there was no significant difference between the two groups.Six months later,the levels of TC,LDL-C,Apo B,Lp(a)in the two groups were lower than before,and the level of HDL-C was higher than before,the difference between the two groups was statistically significant.Although the TG level was lower than before,there was no significant difference between the two groups(P>0.05).The results of repeated measures analysis of variance showed that the LDL-C level of the experimental group decreased progressively with time,and the differences of LDL-C value between different time points were statistically significant(P<0.05).4.The incidence of adverse cardiovascular events during the follow-up period was 8.1% in the experimental group.One patient was hospitalized for heart failure,one patient was hospitalized for recurrent unstable angina,and one patient was hospitalized for coronary revascularization.The incidence of MACE in the control group was 22.4%.Among them,1 patient died of cardiovascular disease,1 patient had recurrent myocardial infarction,2patients were hospitalized for heart failure,4 patients were hospitalized for unstable angina,and 3 patients underwent coronary revascularization.There was no significant difference in single cardiovascular events between the two groups(P>0.05),but there was a significant difference in the incidence of composite adverse cardiovascular events between the control group and the experimental group(P<0.05),and the incidence of major adverse cardiovascular events in the experimental group was significantly lower than that in the control group.5.Adverse drug reactions: during the follow-up period,1 patient in the experimental group had discomfort at the injection site,which was relieved by himself,and 1 patient had gastrointestinal reaction.In the control group,2patients had muscle pain and 2 patients had abnormal liver function.The other patients did not complain of special adverse drug reactions.There was no significant difference in adverse reactions between the two groups(P>0.05).6.The comparison of inflammatory indicators between the two groups showed that compared with the control group,the levels of related inflammatory indicators(IL-1β,TNF-α)in the experimental group were significantly reduced,and the differences between the groups at each time point were statistically significant(IL-1β : 37.1±4.6pg/ ml-36.8 ±5.3 pg/ml at baseline,8.2±1.5pg/ ml-16.3 ±1.8pg/ml at 3 months,and 7.5±0.9pg/ ml-16.1±0.6pg/ml at 6 months,P<0.05;TNF-α : 44.7±3.4 pg/ ml-46.2 ±2.4 pg/ml at baseline,15.1±3.5 pg/ ml-23.5 ±5.2 pg/ml at 3 months,10.5±2.3 pg/ ml-20.8±2.6 pg/ml at 6 months,P<0.05).There was no significant difference in hs-CRP between the two groups at each time point(P>0.05).Conclusions:For patients with acute ST-segment elevation myocardial infarction,the combination of lipid-lowering therapy with alirocumab not only significantly reduces the levels of related blood lipid indicators,but also has a trend of reducing MACE,and also has a trend of reducing inflammatory indicators.At thesame time,the clinical application is safe and well tolerated.更多还原