王悦,刘倍倍,陈蕾蕾,王越,王志强,张晓江,陈青,李宇,吴小凡

• 1:首都医科大学附属北京安贞医院心内科

摘要(Abstract)：

目的探讨性别是否对急性冠状动脉综合征(ACS)患者经皮冠状动脉介入治疗(PCI)术后接受小剂量替格瑞洛疗效产生影响。方法连续入选2017年8月至2019年7月在首都医科大学附属北京安贞医院PCI术后3个月复查的ACS患者2110例,根据抗血小板治疗策略的不同分为两组:标准剂量替格瑞洛组(90 mg,每日2次;1830例)或小剂量替格瑞洛组(45 mg,每日2次;280例)。利用倾向性评分得出基线无显著差异的四组,标准剂量替格瑞洛男性患者(387例)、小剂量替格瑞洛男性患者(188例)、标准剂量替格瑞洛女性患者(161例)和小剂量替格瑞洛女性患者(88例),评估各组患者分组后9个月出血事件及主要不良心脑血管事件(包括心原性死亡、心肌梗死和卒中)的发生情况。结果无论是男性患者还是女性患者,与标准剂量的替格瑞洛相比,小剂量替格瑞洛均显著降低了总出血事件及出血学术研究联合会(BARC) 1型出血事件的风险(均P<0.05);而BARC 2型出血,BARC 2、3或5型出血,BARC 3或5型出血及主要不良心脑血管事件发生率比较,差异均无统计学意义(均P>0.05)。结论与标准剂量替格瑞洛相比,小剂量替格瑞洛可能降低了ACS患者PCI术后小出血风险,未增加主要不良心脑血管事件的发生,这种获益可能不存在性别差异。

关键词(KeyWords)： 急性冠状动脉综合征;替格瑞洛;剂量;性别

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金（81670317、81470492）;; 首都卫生发展科研专项项目（首发2018-2-2064）;; 北京市教育委员会科技计划重点项目（KZ202010025045）

作者(Author): 王悦,刘倍倍,陈蕾蕾,王越,王志强,张晓江,陈青,李宇,吴小凡

参考文献(References)：

• [1]张亮，袁铭，曹丰.半量替格瑞洛对高龄急性冠脉综合征合并慢性肾功能不全患者的疗效和安全性研究.心脏杂志，2017,29(3):300-303.
• [2] Kovacic JC, Mehran R, Karajgikar R, et al. Female gender and mortality after percutaneous coronary intervention:results from a large registry. Catheter Cardiovasc Interv, 2012, 80(4):514-521.
• [3] Woo JS, Kim W, Ha SJ, et al. Impact of gender dif ferences on long term outcomes after successful percutaneous coronary intervention in patients with acute myocardial infarction. Int J Cardiol, 2010, 145(3):516-518.
• [4]中国医师协会急诊医师分会，国家卫健委能力建设与继续教育中心急诊学专家委员会，中国医疗保健国际交流促进会急诊急救分会.急性冠脉综合征急诊快速诊治指南（2019）.中华急诊医学杂志，2019,28(4):421-428.
• [5] Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials:a case for standardized definitions.Circulation, 2007, 115(17):2344-2351.
• [6] Thygesen K, Alpert JS, Jaf fe AS,et al. Fourth universal defi nition of myocardial infarction(2018). J Am Coll Cardiol, 2018, 72(18):2231-2264.
• [7] Hahn JY, Song YB, Oh JH, et al. Ef fect of P2Y12 inhibitor monotherapy vs dual antiplatelet therapy on cardiovascular events in patients undergoing percutaneous coronary intervention:the SMART-CHOICE randomized clinical trial. JAMA, 2019, 321(24):2428-2437.
• [8] Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding defi nitions for cardiovascular clinical trials:a consensus report from the Bleeding Academic Research Consortium. Circulation,2011, 123(23):2736-2747.
• [9] Teng R. Ticagrelor:pharmacokinetic,pharmacodynamic and pharmacogenetic profi le:an update. Clin Pharmacokinet,2015, 54(11):1125-1138.
• [10] Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med, 2009, 361(11):1045-1057.
• [11] Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS:the Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology(ESC)and of the European Association for Cardio-Thoracic Surgery(EACTS). Eur Heart J, 2018,39(3):213-260.
• [12]中华医学会心血管病学分会介入心脏病学组，中国医师协会心血管内科医师分会血栓防治专业委员会，中华心血管病杂志编辑委员会.中国经皮冠状动脉介入治疗指南（2016）.中华心血管病杂志，2016, 44(5):382-400.
• [13] Sun Y, Li C, Zhang L, et al. Clinical outcomes after ticagrelor and clopidogrel in Chinese post-stented patients. Atherosclerosis,2019, 290:52-58.
• [14] Park DW, Kwon O, Jang JS, et al. Clinically signifi cant bleeding with ticagrelor versus clopidogrel in Korean patients with acute coronary syndromes intended for invasive management:a randomized clinical trial. Circulation, 2019, 140(23):1865-1877.
• [15] Yun JE, Kim YJ, Park JJ, et al. Safety and ef fectiveness of contemporary P2Y12 inhibitors in an east Asian population with acute coronary syndrome:a nationwide population-based cohort study. J Am Heart Assoc, 2019, 8(14):e012078.
• [16] Li H, Butler K, Yang L, et al. Pharmacokinetics and tolerability of single and multiple doses of ticagrelor in healthy Chinese subjects:an open-label, sequential, two-cohort, single-centre study. Clin Drug Investig, 2012, 32(2):87-97.
• [17] Jeon HS, Kim MJ, Choi HY, et al. Pharmacokinetics and pharmacodynamics of ticagrelor and prasugrel in healthy male Korean volunteers. Clin Ther, 2015, 37(3):563-573.
• [18] Choi KN, Jin HY, Shin HC, et al. Comparison of the antiplatelet ef fects of once and twice daily low-dose ticagrelor and clopidogrel after percutaneous coronary intervention. Am J Cardiol, 2017, 120(2):201-206.
• [19]陈夏欢，刘梅林，黄波，等.老年冠心病患者经皮冠状动脉介入治疗服用不同剂量替格瑞洛疗效的研究.中国介入心脏病学杂志，2017, 25(11):617-621.
• [20] Wang Y, Liu B, Chen L, et al. Safety and e ffi cacy of lowdose ticagrelor in Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention. Platelets, 2021.[Online ahead of print]
• [21] Husted S, James SK, Bach RG, et al. The efficacy of ticagrelor is maintained in women with acute coronary syndromes participating in the prospective, randomized, PLATelet inhibition and patient outcomes(PLATO)trial. Eur Heart J,2014, 35(23):1541-1550.
• [22] Lau ES, Braunwald E, Murphy SA, et al. Potent P2Y12Inhibitors in men versus women:a collaborative Meta-analysis of randomized trials. J Am Coll Cardiol, 2017, 69(12):1549-1559.
• [23] Grodecki K, Huczek Z, Scislo P, et al. Gender-related dif ferences in post-discharge bleeding among patients with acute coronary syndrome on dual antiplatelet therapy:A Blee MACS sub-study. Thromb Res, 2018, 168:156-163.
• [24] Kelsey SF, James M, Holubkov AL, et al. Results of percutaneous transluminal coronary angioplasty in women. 1985-1986 national heart, lung, and blood institute’s coronary angioplasty registry. Circulation, 1993, 87(3):720-727.
• [25] Cowley MJ, Mullin SM, Kelsey SF, et al. Sex dif ferences in early and long-term results of coronary angioplasty in the NHLBI PTCA registry. Circulation, 1985, 71(1):90-97.
• [26] Hao Y, Liu J, Liu J, et al. Sex differences in in-hospital management and outcomes of patients with acute coronary syndrome. Circulation, 2019, 139(15):1776-1785.
• [27] Gargiulo G, Ariotti S, Santucci A, et al. Impact of sex on 2-year clinical outcomes in patients treated with 6-month or24-month dual-antiplatelet therapy duration:a pre-specified analysis from the PRODIGY trial. JACC Cardiovasc Interv,2016, 9(17):1780-1789.
• [28] Yu J, Mehran R, Grinfeld L, et al. Sex-based dif ferences in bleeding and long term adverse events after percutaneous coronary intervention for acute myocardial infarction:three year results from the HORIZONS-AMI trial. Catheter Cardiovasc Interv,2015, 85(3):359-368.