仿制与原研替格瑞洛抗血小板治疗有效性和安全性的比较研究

A comparative study on efficacy and safety of generic and original ticagrelor in antiplatelet therapy

目的比较浙江海正药业股份有限公司生产的替格瑞洛片(仿制药)与阿斯利康制药有限公司生产的替格瑞洛片(原研药)抗血小板治疗的有效性和安全性。方法研究设计为回顾性队列研究, 研究对象选自2020年1月至2021年7月在大连医科大学附属第一医院行经皮冠状动脉介入(PCI)治疗且术后使用替格瑞洛片抗血小板治疗的急性冠状动脉综合征(ACS)患者。通过医院电子病历系统, 收集符合纳入标准患者的病历资料并提取相关临床数据(年龄、性别、合并疾病、入院时血脂水平、PCI指征、PCI术后抗血小板治疗方案、用药12个月内疗效和安全性评估终点事件发生情况等)。将患者分为仿制药组和原研药组, 为排除混杂因素的干扰, 对患者进行倾向性评分匹配(PSM)。有效性评估指标为用药12个月内主要终点(心源性死亡、卒中、靶血管重建、再发梗死)和次要终点(全因死亡、外周动脉闭塞、支架内血栓形成、心绞痛发作)事件发生率, 安全性主要评价指标为用药12个月内出血事件发生率。结果纳入研究的患者共1 486例, 仿制药组734例, 原研药组752例。仿制药组患者中女性占比、PCI指征为不稳定心绞痛者占比、入院时高密度脂蛋白胆固醇水平高于原研药组;合并高脂血症患者占比、PCI指征为ST段抬高型心肌梗死者占比低于原研药组(均P<0.05)。PSM后仿制药和原研药组各690例患者, 各项临床特征比较差异均无统计学意义(均P>0.05)。PSM前、后仿制药组患者主要终点、次要终点和出血事件发生率与原研药组比较差异均无统计学意义[PSM前:12.1%(89/734)比10.9%(82/752), 10.8%(79/734)比8.4%(63/752), 0.3%(2/734)比0.5%(4/752);PSM后:12.6%(87/690)比12.3%(85/690), 11.0%(76/690)比8.3%(57/690), 0.3%(2/690)比0.4%(3/690);均P>0.05]。2组患者均无一例死亡。出血主要表现为鼻出血和皮下瘀点, 未导致抗血小板治疗中断。结论浙江海正药业股份有限公司仿制替格瑞洛片用于PCI术后ACS患者抗血小板治疗的有效性及安全性与原研药基本一致。

Objective To compare the efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co.,Ltd.(the generic drug)and ticagrelor tablets produced by AstraZeneca Pharmaceutical Co.,Ltd.(the original drug)in antiplatelet therapy.Methods The study design was a retrospective cohort study.The subjects were patients who underwent percutaneous coronary intervention(PCI)for acute coronary syndrome(ACS)and postoperative antiplatelet therapy with ticagrelor tablets at First Affiliated Hospital of Dalian Medical University during January 2020 to July 2021.Through the hospital electronic medical record system,relevant clinical data of patients(age,gender,comorbidities,blood lipid level on admission,PCI indications,antiplatelet treatment regimen,efficacy and safety assessment endpoint events within 12 months of treatment,etc.)were collected.The patients were divided into the generic drug group and the original drug group.To exclude confounders,propensity score matching(PSM)method was used.The efficacy evaluation index was the incidence of the primary endpoint events(cardiogenic death,stroke,target revascularization,recurrent infarction)and secondary endpoint events(all-cause mortality,peripheral artery occlusion,stent thrombosis,angina attacks)within 12 months of treatment.The safety evaluation index was the incidence of bleeding event within 12 months of treatment.Results A total of 1486 patients were included in this study,including 734 in the generic drug group and 752 in the original drug group.The proportion of women and unstable angina,and the level of high-density lipoprotein cholesterol were higher than those in the original drug group(all P<0.05).The proportion of patients with hyperlipidemia and ST-segment elevation myocardial infarction were lower than those in the original drug group(both P<0.05).After PSM,690 patients were enrolled in the generic drug group and 690 patients in the original drug group(all P>0.05).No differences in the comparison of clinical features between the 2 groups was significant(all P>0.05).No differences in the incidences of primary endpoints,secondary endpoints,and bleeding events between the 2 groups was significant before and after PSM[before PSM:12.1%(89/734)vs.10.9%(82/752),10.8%(79/734)vs.8.4%(63/752),0.3%(2/734)vs.0.5%(4/752);after PSM:12.6%(87/690)vs.12.3%(85/690),11.0%(76/690)vs.8.3%(57/690),0.3%(2/690)vs.0.4%(3/690);all P>0.05].No death occurred in patients of both groups.Bleeding is predominantly characterized by epistaxis and subcutaneous petechiae,which did not lead to interruption of antiplatelet therapy.Conclusion The efficacy and safety of ticagrelor tablets produced by Zhejiang Hisun Pharmaceutical Co.,Ltd.for antiplatelet therapy in ACS patients after PCI surgery were basically the same as those of the original drug.