目的 评价光比浊法(light transmittance aggregometry, LTA)和血小板功能分析法(VerifyNow)对抗血小板药物药效学指标-血小板反应性检测结果的一致性。方法 纳入北京大学第一医院收治的,规律服用P2Y12受体抑制剂氯吡格雷或替格瑞洛的冠心病患者,在服药前采集谷浓度血样,使用LTA和VerifyNow两种检测方法对药效学指标血小板反应性进行检测,对两种检测方法结果之间的相关性进行spearman相关性分析;然后分别按LTA和VerifyNow将患者判定为血小板高反应性(high platelet reactivity, HPR)和血小板低反应性(low platelet reactivity,LPR),比较两种方法结果的一致性;最后根据抗血小板治疗药物将患者分为氯吡格雷组和替格瑞洛组,分析在不同药物组LTA和VerifyNow两种检测结果之间的相关性。结果 共纳入116名患者,其中氯吡格雷组39人,替格瑞洛组77人。血小板反应性检测结果显示LTA和VerifyNow检测结果显著相关性,r=0.565,P=3.99×10-11。但在HPR和LPR的判定方面,两种方法一致性中等(kappa=0.403)。氯吡格雷组的两种检测方法结果具有相关性,r=0.526,P=5.89×10-4。替格瑞洛组血小板反应性显著低于氯吡格雷组,药效更好,但两种检测方法结果不具有相关性,r=0.120,P=0.299。结论 LTA和VerifyNow检测值整体具有相关性,但在血小板反应性较低的替格瑞洛组无显著相关,两种检测方法判定出的HPR和LPR一致性中等,需要进一步改进判定的阈值。
Abstract
OBJECTIVE To evaluate the consistency of platelet reactivity test results between light transmission aggregometry (LTA) and VerifyNow. METHODS In Peking University First Hospital, patients with coronary heart disease who regularly took P2Y12 receptor inhibitor clopidogrel or ticagrelor were included. Blood sample of trough concentration was collected before taking P2Y12 receptor inhibitor. The pharmacodynamic indexes platelet reactivity were detected by LTA and VerifyNow. The correlation between the results of the two detection methods was evaluated by spearman correlation analysis. Then the high platelet reactivity (HPR) and low platelet reactivity (LPR) were determined according to LTA and VerifyNow respectively, and the consistency of the results of the two methods was compared. Finally, patients using clopidogrel and ticagrelor were divided into two groups to evaluate the correlation between LTA and Verify Now, respectively. RESULTS A total of 116 patients were enrolled, including 39 patients of clopidogrel group and 77 patients of ticagrelor group. There was significant correlation between LTA and VerifyNow(r=0.565, P=3.99×10-11). However, in the determination of HPR and LPR, the consistency of the two methods was medium (kappa=0.403). The results of the two methods in clopidogrel group were correlated(r=0.526, P=5.89×10-4). Compared with clopidorel group, the platelet reactivity of ticagrelor group was significantly lower, which indicated better efficacy. However, there was no correlation between the results of LTA and VerifyNow in different P2Y12 receptor groups. CONCLUSION Except for the detection of LPR in ticagrelor group, platelet reactivity detected by LTA and VerifyNow is mostly correlated. The consistency of HPR and LPR determined by the two detection methods is medium, and the judgment threshold needs to be further improved.
关键词
光比浊法 /
血小板功能分析法 /
P2Y12受体 /
血小板反应性 /
冠心病 /
氯吡格雷 /
替格瑞洛
{{custom_keyword}} /
Key words
LTA /
VerifyNow /
P2Y12 receptor /
platelet reactivity /
coronary heart disease /
clopidogrel /
ticagrelor
{{custom_keyword}} /
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] WIRTZ P H, VON KÄNEL R. Psychological stress, inflammation, and coronary heart disease. Curr Cardiol Rep, 2017, 19(11):111.Doi: 10.1007/s11886-017-0919-x.
[2] GILLETTE M, MORNEAU K, HOANG V, et al. Antiplatelet management for coronary heart disease: advances and challenges. Curr Atheroscler Rep, 2016, 18(6):35. Doi: 10.1007/s11883-016-0581-6.
[3] PEREIRA N L, RIHAL C S, SO D Y F, et al. Clopidogrel pharmacogenetics. Circ Cardiovasc Interv, 2019, 12(4):e007811. Doi: 10.1161/CIRCINTERVENTIONS.119.007811.
[4] NGUYEN T A, DIODATI J G, PHARAND C. Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol, 2005, 45(8):1157-1164.
[5] FEFER P, HOD H, MATETZKY S. Clopidogrel resistance--the cardiologist′s perspective. Platelets, 2007, 18(3):175-181.
[6] TANG Y D, WANG W, YANG M, et al. Randomized comparisons of double-dose clopidogrel or adjunctive cilostazol versus standard dual antiplatelet in patients with high posttreatment platelet reactivity: results of the CREATIVE trial. Circulation, 2018, 137(21):2231-2245.
[7] ADAMSKI P, BUSZKO K, SIKORA J, et al. Determinants of high platelet reactivity in patients with acute coronary syndromes treated with ticagrelor. Sci Rep, 2019, 9(1):3924.Doi: 10.1038/s41598-019-40628-0.
[8] CHOI K N, JIN H Y, SHIN H C, et al. Comparison of the antiplatelet effects of once and twice daily low-dose ticagrelor and clopidogrel after percutaneous coronary intervention. Am J Cardiol, 2017, 120(2):201-206.
[9] NAWARSKAS J J, MONTOYA T N. Switching from ticagrelor or prasugrel to clopidogrel. Cardiol Rev, 2018, 26(2):107-111.
[10] THOMAS M R, STOREY R F. Clinical significance of residual platelet reactivity in patients treated with platelet P2Y12 inhibitors. Vascul Pharmacol, 2016, 84:25-27.
[11] SHAO T, CHENG Y, JIN J, et al. A comparison of three platelet function tests in ischemic stroke patients with antiplatelet therapy. J Clin Neurosci, 2020, 78:91-96.
[12] PANICCIA R, PRIORA R, LIOTTA A A, et al. Platelet function tests: a comparative review. Vasc Health Risk Manag, 2015, 11:133-148.
[13] MARKEL K M, AVGERINOS E D. Clopidogrel resistance in lower extremity arterial endovascular interventions. Curr Pharm Des, 2018, 24(38):4554-4557.
[14] ALVITIGALA B Y, GOONERATNE L V, CONSTANTINE G R, et al. Pharmacokinetic, pharmacodynamic, and pharmacogenetic assays to monitor clopidogrel therapy. Pharmacol Res Perspect, 2020, 8(6):e00686. Doi: 10.1002/prp2.686.
[15] GURBEL P A, BLIDEN K P, BUTLER K, et al. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation, 2010, 121(10):1188-1199.
[16] VARENHORST C, JAMES S, ERLINGE D, et al. Assessment of P2Y(12) inhibition with the point-of-care device VerifyNow P2Y12 in patients treated with prasugrel or clopidogrel coadministered with aspirin. Am Heart J, 2009, 157(3):562.e561-569.
[17] TANTRY U S, 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.
[18] JEONG Y H, BLIDEN K P, ANTONINO M J, et al. Usefulness of the VerifyNow P2Y12 assay to evaluate the antiplatelet effects of ticagrelor and clopidogrel therapies. Am Heart J, 2012, 164(1):35-42.
[19] LE BLANC J, MULLIER F, VAYNE C, et al. Advances in platelet function testing-light transmission aggregometry and beyond. J Clin Med, 2020, 9(8):2636. Doi: 10.3390/jcm9082636..
[20] MADSEN E H, SAW J, KRISTENSEN S R, et al. Long-term aspirin and clopidogrel response evaluated by light transmission aggregometry, VerifyNow, and thrombelastography in patients undergoing percutaneous coronary intervention. Clin Chem, 2010, 56(5):839-847.
[21] VAN WERKUM J W, HARMSZE A M, ELSENBERG E H, et al. The use of the VerifyNow system to monitor antiplatelet therapy: a review of the current evidence. Platelets, 2008, 19(7):479-488.
[22] ARADI D, TORNYOS A, PINTÉR T, et al. Optimizing P2Y12 receptor inhibition in patients with acute coronary syndrome on the basis of platelet function testing: impact of prasugrel and high-dose clopidogrel. J Am Coll Cardiol, 2014, 63(11):1061-1070.
[23] PARK Y, JEONG Y H, KIM I S, et al. The concordance and correlation of measurements by multiple electrode and light transmittance aggregometries based on the pre-defined cutoffs of high and low on-treatment platelet reactivity. Platelets, 2012, 23(4):290-298.
[24] JANSSEN P W, TEN BERG J M. Platelet function testing and tailored antiplatelet therapy. J Cardiovasc Transl Res, 2013, 6(3):316-328.
[25] SIBBING D, SCHULZ S, BRAUN S, et al. Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. J Thromb Haemost, 2010, 8(2):250-256.
[26] VRIES M J, BOUMAN H J, OLIE R H, et al. Determinants of agreement between proposed therapeutic windows of platelet function tests in vulnerable patients. Eur Heart J Cardiovasc Pharmacother, 2017, 3(1):11-17.
[27] LEMESLE G, LANDEL J B, BAUTERS A, et al. Poor agreement between light transmission aggregometry, Verify Now P2Y and vasodilatator-stimulated phosphoprotein for clopidogrel low-response assessment: a potential explanation of negative results of recent randomized trials. Platelets, 2014, 25(7):499-505.
[28] LORDKIPANIDZÉ M, PHARAND C, NGUYEN T A, et al. Comparison of four tests to assess inhibition of platelet function by clopidogrel in stable coronary artery disease patients. Eur Heart J, 2008, 29(23):2877-2885.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(1011 KB)
