任德旺,刘飞,徐东

• 1:首都医科大学附属北京天坛医院心脏及大血管外科

摘要(Abstract)：

<正>阿司匹林和P2Y12抑制药的双联抗血小板治疗(dual antiplatelet therapy,DAPT)已成为急性冠状动脉综合征(acute coronary syndrome,ACS)和经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后患者管理的基石,可以有效抑制血小板反应性,显著降低不良心血管事件的发生率,所以在国内外指南中均被列为Ⅰ类推荐[1-2]。但在DAPT期间,个体间对抗血小板药物治疗反应存在差异,即血小板反应多样性(variability of platelet response,VPR)。目前已有多项研究表明高血小板反应性(high platelet reactivity,HPR)与缺血事件发生具有一定的相关性[3-5],尤其与近期急性或亚急性支架内血栓形成具有较强相关性[6]。而低血小板反应性(low

关键词(KeyWords)： 抗血小板治疗;血小板反应多样性;血小板功能检测

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 任德旺,刘飞,徐东

参考文献(References)：

• [1] Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J, 2019,40(2):87-165.
• [2]中华医学会心血管病学分会，中华心血管病杂志编辑委员会.抗血小板治疗中国专家共识.中华心血管病杂志，2013,41(3):183-194.
• [3] Spiliopoulos S, Pastromas G. Current status of high on-treatment platelet reactivity in patients with coronary or peripheral arterial disease:Mechanisms, evaluation and clinical implications. World J Cardiol, 2015,7(12):912-921.
• [4] Rinaldi MJ, Kirtane A, Xu K, et al. Impact of point-of-care platelet function testing among patients with and without acute coronary syndromes undergoning PCI with drug-eluting stents:AN ADAPTDES SUBSTUDY. J Am Coll Cardiol, 2012,59(13):E268.
• [5] Mangiacapra F, Colaiori I, Ricottini E, et al. Impact of platelet reactivity on 5-year clinical outcomes following percutaneous coronary intervention:a landmark analysis. J Thromb Thrombolysis, 2018,45(4):496-503.
• [6] Siller-Matula JM, Trenk D, Schrfir K, et al. Response variability to P2Y12, receptor inhibitors:expectations and reality. JACC Cardiovasc Interv, 2013,6(11):1111-1128.
• [7] Tantry US, Bonello L, Aradi D, et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol, 2013,62(24):2261-2273.
• [8] Aradi D, Storey RF, Komócsi A, et al. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J, 2014,35(4):209-215.
• [9] Snoep JD, Hovens MM, Eikenboom JC, et al. Association of laboratory-defined aspirin resistance with a higher risk of recurrent cardiovascular events. Arch Intern Med, 2007,167(15):1593-1595.
• [10] Grosser T, Fries S, Lawson JA, et al. Drug resistance and pseudoresistance. Circulation, 2013,127(3):377-385.
• [11] Chung CJ, Kirtane AJ, Zhang Y, et al. Impact of high on-aspirin platelet reactivity on outcomes following successful percutaneous coronary intervention with drug-eluting stents. Am Heart J, 2018,205:77-86.
• [12]中华医学会心血管病学会.抗血小板药物治疗反应多样性临床检测和处理的中国专家建议.中华心血管病杂志，2014,42(12):986-991.
• [13] Jovanovic L, Antonijevic N, Novakovic T, et al. Practical aspects of monitoring of antiplatelet therapy. Semin Thromb Hemost, 2017,43(1):14-23.
• [14]张昌琳，朱宁.细胞色素P450 2C19多态性与对氯吡格雷的反应性研究进展.心血管病学进展，2011,32(6):858-862.
• [15] Joo HJ, Ahn SG, Park JH, et al. Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention:A prospective multicentre registry study. Sci Rep, 2018,8(1):1229.
• [16] Zhuo ZL, Xian HP, Long Y, et al. Association between CYP2C19and ABCB1 polymorphisms and clopidogrel resistance in clopidogreltreated Chinese patients. Anatol J Cardiol, 2018,19(2):123-129.
• [17] Gurbel PA, Bergmeijer TO, Tantry US, et al. The effect of CYP2C19 gene polymorphisms on the pharmacokinetics and pharmacodynamics of prasugrel 5-mg, prasugrel 10-mg and clopidogrel 75-mg in patients with coronary artery disease. Thromb Haemost, 2014,112(3):589-597.
• [18] Chen YC, Lin FY, Lin YW, et al. DAPT plus cilostazol is better than traditional DAPT or aspirin plus ticagrelor as elective PCI for intermediate-to-highly complex cases:prospective, randomized, PRUBased study in Taiwan. Am J Cardiovasc Drugs,2019,19(1):75-86.
• [19] Verdoia M, Pergolini P, Nardin M, et al. Prevalence and predictors of high-on treatment platelet reactivity during prasugrel treatment in patients with acute coronary syndrome undergoing stent implantation. J Cardiol, 2019,73(3):198-203.
• [20] Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J, 2018,39(2):119-177.
• [21]徐娜，袁晋青.血小板功能检测对冠心病患者抗血小板治疗出血事件的预测价值.中国循环杂志，2017,32(2):193-196.
• [22]李梦梦，李全，张晓玲，等.血小板功能系列检测对接受复杂经皮冠状动脉介入治疗患者临床结局的预测价值.中华心血管病杂志，2017,45(9):770-776.
• [23] Cattaneo M, Cerletti C, Harrison P, et al. Recommendations for the standardization of light transmission aggregometry:a consensus of the working party from the platelet physiology subcommittee of SSC/ISTH. J Thromb Haemost, 2013,11(6):1183-1189.
• [24] Harrison P, Mackie I, Mumford A, et al. Guidelines for the laboratory investigation of heritable disorders of platelet function. Br J Haematol, 2011,155(1):30-44.
• [25] Othman M, Kaur H. Thromboelastography(TEG). Methods Mol Biol, 2017,1646:533-543.
• [26] Tang XF, Han YL, Zhang JH, et al. Comparing of light transmittance aggregometry and modified thrombelastograph in predicting clinical outcomes in Chinese patients undergoing coronary stenting with clopidogrel. Chin Med J(Engl), 2015,128(6):774-779.
• [27] Gurbel PA, Bliden KP, Navickas IA, et al. Adenosine diphosphateinduced platelet-fibrin clot strength:A new thrombelastographic indicator of long-term poststenting ischemic events. Am Heart J,2010,160(2):346-354.
• [28] Karon BS, Tolan NV, Koch CD, et al. Precision and reliability of5 platelet function tests in Healthy Volunteers and Donors on Daily Antiplatelet Agent Therapy. Clin Chem, 2014,60(12):1524-1531.
• [29]张涌，聂小燕，刘健，等.血栓弹力图法与光学比浊法评价急性冠状动脉综合征患者氯吡格雷反应性的临床研究.中国介入心脏病学杂志，2015,23(1):22-26.
• [30] Aradi D, Kirtane A, Bonello L, et al. Bleeding and stent thrombosis on P2Y12-inhibitors:collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention. Eur Heart J, 2015,36(27):1762-1771.
• [31] Mikkelsson J, Paana T, Lepantalo A, et al. Personalized ADPreceptor inhibition strategy and outcomes following primary PCI for STEMI(PASTOR study). Int J Cardiol, 2016,202:463-466.
• [32] Angiolillo DJ, Franchi F, Waksman R, et al. Effects of ticagrelor versus clopidogrel in troponin-negative patients with low-risk ACS undergoing Ad Hoc PCI. J Am Coll Cardiol, 2016,67(6):603-613.
• [33] Koltowski L, Tomaniak M, Aradi D, et al. Optimal antiplatelet pharmacotherapy guided by bedside genetic or functional testing in elective PCI patients:A pilot study:ONSIDE TEST pilot. Cardiol J,2017,24(3):284-292.
• [34] Rinaldi MJ, Gohs FX, Kirtane AJ, et al. Impact of point-of-care platelet function testing among patients with and without acute coronary syndromes undergoing percutaneous coronary intervention with drug-eluting stents(from the ADAPT-DES Study). Am J Cardiol,2019,123(4):549-557.
• [35] Palmerini T, CalabròP, Piscione F, et al. Impact of gene polymorphisms, platelet reactivity, and the SYNTAX score on1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention:the GEPRESS study. JACC Cardiovasc Interv, 2014,7(10):1117-1127.
• [36] Liang Y, Johnston M, Hirsh J, et al. Relation between clopidogrel active metabolite levels and different platelet aggregation methods in patients receiving clopidogrel and aspirin. J Thromb Thrombolysis,2012,34(4):429-436.
• [37] Cuisset T, Grosdidier C, Loundou AD, et al. Clinical implications of very low on-treatment platelet reactivity in patients treated with thienopyridine:the POBA study(predictor of bleedings with antiplatelet drugs). JACC Cardiovasc Interv, 2013,6(8):854-863.
• [38] Laine M, Toesca R, Berbis J, et al. Platelet reactivity evaluated with the VASP assay following ticagrelor loading dose in acute coronary syndrome patients undergoing percutaneous coronary intervention. Thromb Res, 2013,132(1):e15-e18.
• [39] Bonello L, Mancini J, Pansieri M, et al. Relationship between post treatment platelet reactivity and ischemic and bleeding events at one year follow-up in acute coronary syndrome patients receiving prasugrel. J Thromb Haemost, 2012,10(10):1999-2005.
• [40] Price MJ, Angiolillo DJ, Teirstein PS, et al. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention:a time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay:Impact on Thrombosis and Safety(GRAVITAS)trial. Circulation, 2011,124(10):1132-1137.
• [41] Siller-Matula JM, Gruber C, Francesconi M, et al. The net clinical benefit of personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention. Clin Sci(Lond),2015,128(2):121-130.
• [42] Mayer K, Schulz S, Bernlochner I, et al. A comparative cohort study on personalised antiplatelet therapy in PCI-treated patients with high on-clopidogrel platelet reactivity. Results of the ISAR-HPR registry. Thromb Haemost, 2014,112(2):342-351.
• [43] Zhang Y, Zhang P, Li Z, et al. Benefits of laboratory personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention:A meta-analysis of randomized controlled trials. Cardiol J, 2018,25(1):128-141.
• [44] Price MJ, Berger PB, Teirstein PS, et al. Standard-vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention:the GRAVITAS randomized trial. JAMA,2011,305(11):1097-1105.
• [45] Trenk D, Stone GW, Gawaz M, et al. A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents:results of the TRIGGERPCI(Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel)Study. J Am Coll Cardiol, 2012, 59(24):2159-2164.
• [46] Collet JP, Cuisset T, RangéG, et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med,2012,367(22):2100-2109.
• [47] Cayla G, Cuisset T, Silvain J, et al. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome(ANTARCTIC):an open-label, blindedendpoint, randomised controlled superiority trial. Lancet, 2016,388(10055):2015-2022.