Predictive value of the platelet function PFA-200 P2Y on the secondary prevention of acute ischemic stroke with clopidogrel

doi:10.3969/j.issn.1004-583X.2023.11.003

Abstract

Abstract:

Objective To explore the predictive value of the platelet function analyzer (PFA)-200 P2Y testing in evaluating the clinical outcome of patients with acute ischemic stroke. Methods From January 2021 to December 2021, clinical data of patients with acute ischemic stroke and long-term use of clopidogrel for secondary prevention were collected. The patients were followed up for a median of 1 year. They were divided into ischemic vascular event group and non-ischemic vascular event group according to their prognosis. The closure time (CT) was measured using the PFA-200 P2Y analyzer to detect platelet function. The recurrence of ischemic vascular events during the follow-up period was observed. Logistic regression was used to analyze the risk factors for the recurrence of ischemic vascular events, and the receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of the PFA-200 P2Y testing for the recurrence of ischemic vascular events. Results A total of 142 patients with acute ischemic stroke were included, of whom 24 (16.9%) had recurrent ischemic vascular events during the follow-up period. The level of P2Y in the ischemic vascular event group was significantly lower than that of the non-ischemic vascular event group, and the modified Rankin Scale (mRS) score was significantly higher ( $P$ <0.05). Logistic regression analysis showed that the PFA-200 P2Y testing was the independent risk factor for ischemic vascular events in the prognosis of acute ischemic stroke ( $P$ <0.05). ROC results showed that the PFA-200 P2Y testing had a good predictive value for ischemic vascular events in patients receiving clopidogrel for secondary prevention of ischemic stroke, with an area under the curve (AUC) of 0.766 (95% $C I$ : 0.644, 0.887). Conclusion Low P2Y level is an independent risk factor for recurrence of ischemic vascular events in patients with acute ischemic stroke and the use of clopidogrel for secondary prevention, and PFA-200 P2Y results have a certain predictive value for ischemic vascular events within 1 year.

Key words: clopidogrel, acute ischemic stroke, stroke, platelet function, high on-treatment platelet reactivity

CLC Number:

R743

Luo Weigang, Xu Yuzhu, Zhang Lingyan, Wu Xiangyun, Bu Wei, Ren Huiling. Predictive value of the platelet function PFA-200 P2Y on the secondary prevention of acute ischemic stroke with clopidogrel[J]. Clinical Focus, 2023, 38(11): 979-983.

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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2023.11.003

https://huicui.hebmu.edu.cn/EN/Y2023/V38/I11/979

Figures/Tables 4

Tab. 1 Comparison of clinical data between the two groups (M[Q1, Q3])

组别	例数		年龄(岁)			男		吸烟		饮酒			NIHSS评分(分)		mRS评分(分)
缺血性血管事件组	24		70.00(57.50,75.50)			17(70.80)		10(41.70)		11(45.80)			3.00(2.00,4.00)		1.00(0.00,2.00)
无缺血性血管事件组	118		63.00(56.50,71.00)			85(72.00)		46(39.00)		41(34.70)			3.00(2.00,4.00)		0.00(0.00,1.00)
χ²/ $t$ / $Z$ 值			-1.362			0.014		0.060		1.056			-0.072		-2.230
$P$ 值			0.173			0.905		0.806		0.304			0.942		0.026
组别		高血压			糖尿病			卒中史			冠心病			总胆固醇(mmol/L)
缺血性血管事件组		16(66.70)			9(37.50)			11(45.80)			4(16.70)			4.16(3.50,4.62)
无缺血性血管事件组		80(67.80)			44(37.30)			47(39.80)			16(13.60)			4.21(3.43,5.04)
χ²/ $t$ / $Z$ 值		0.012			0.000			0.297			0.159			-0.189
$P$ 值		0.914			0.984			0.585			0.690			0.850
组别	甘油三酯 (mmol/L)			高密度脂蛋白胆固醇(mmol/L)			低密度脂蛋白胆固醇 (mmol/L)		同型半胱氨酸 (μmol/L))			糖化血红蛋白 (%)		P2Y (s)
缺血性血管事件组	1.24(1.01,1.36)			1.02(0.88,1.28)			2.21±0.80		13.70(9.68,21.45)			5.90(5.55,7.00)		63.50(57.25,127.00)
无缺血性血管事件组	1.36(1.03,2.06)			1.02(0.88,1.20)			2.56±0.79		14.50(11.35,18.55)			6.05(5.60,7.00)		127.00(82.00,233.25)
χ²/ $t$ / $Z$ 值	-1.586			-0.726			1.803		-0.473			-0.647		-0.023
$P$ 值	0.113			0.468			0.073		0.639			0.517		0.982

Tab. 1 Comparison of clinical data between the two groups (M[Q1, Q3])

组别	例数		年龄(岁)			男		吸烟		饮酒			NIHSS评分(分)		mRS评分(分)
缺血性血管事件组	24		70.00(57.50,75.50)			17(70.80)		10(41.70)		11(45.80)			3.00(2.00,4.00)		1.00(0.00,2.00)
无缺血性血管事件组	118		63.00(56.50,71.00)			85(72.00)		46(39.00)		41(34.70)			3.00(2.00,4.00)		0.00(0.00,1.00)
χ²/ $t$ / $Z$ 值			-1.362			0.014		0.060		1.056			-0.072		-2.230
$P$ 值			0.173			0.905		0.806		0.304			0.942		0.026
组别		高血压			糖尿病			卒中史			冠心病			总胆固醇(mmol/L)
缺血性血管事件组		16(66.70)			9(37.50)			11(45.80)			4(16.70)			4.16(3.50,4.62)
无缺血性血管事件组		80(67.80)			44(37.30)			47(39.80)			16(13.60)			4.21(3.43,5.04)
χ²/ $t$ / $Z$ 值		0.012			0.000			0.297			0.159			-0.189
$P$ 值		0.914			0.984			0.585			0.690			0.850
组别	甘油三酯 (mmol/L)			高密度脂蛋白胆固醇(mmol/L)			低密度脂蛋白胆固醇 (mmol/L)		同型半胱氨酸 (μmol/L))			糖化血红蛋白 (%)		P2Y (s)
缺血性血管事件组	1.24(1.01,1.36)			1.02(0.88,1.28)			2.21±0.80		13.70(9.68,21.45)			5.90(5.55,7.00)		63.50(57.25,127.00)
无缺血性血管事件组	1.36(1.03,2.06)			1.02(0.88,1.20)			2.56±0.79		14.50(11.35,18.55)			6.05(5.60,7.00)		127.00(82.00,233.25)
χ²/ $t$ / $Z$ 值	-1.586			-0.726			1.803		-0.473			-0.647		-0.023
$P$ 值	0.113			0.468			0.073		0.639			0.517		0.982

Tab. 2 Univariate analysis of indicators related to P2Y and ischemic vascular events(r)

	NIHSS评分	mRS评分	总胆固醇	甘油三酯	高密度脂蛋白胆固醇	低密度脂蛋白胆固醇	同型半胱氨酸	糖化血红蛋白
$r$ 值	-0.028	-0.017	-0.055	0.009	-0.123	0.017	-0.063	0.042
$P$ 值	0.745	0.853	0.518	0.917	0.155	0.845	0.456	0.616

Tab. 2 Univariate analysis of indicators related to P2Y and ischemic vascular events(r)

	NIHSS评分	mRS评分	总胆固醇	甘油三酯	高密度脂蛋白胆固醇	低密度脂蛋白胆固醇	同型半胱氨酸	糖化血红蛋白
$r$ 值	-0.028	-0.017	-0.055	0.009	-0.123	0.017	-0.063	0.042
$P$ 值	0.745	0.853	0.518	0.917	0.155	0.845	0.456	0.616

Tab. 3 Multivariate Logistic regression analysis of influencing factors of ischemic vascular events

变量	β	$S E$	Wald χ²值	$P$ 值	$O R$ 值	95% $C I$
P2Y	-0.010	0.005	5.078	0.024	0.990	0.981~0.999
MRS评分	0.244	0.183	1.779	0.182	1.276	0.892~1.827
甘油三酯	-0.353	0.408	0.746	0.388	0.703	0.316~1.565
低密度脂蛋白	-0.506	0.364	1.925	0.165	0.603	0.295~1.232

Tab. 3 Multivariate Logistic regression analysis of influencing factors of ischemic vascular events

变量	β	$S E$	Wald χ²值	$P$ 值	$O R$ 值	95% $C I$
P2Y	-0.010	0.005	5.078	0.024	0.990	0.981~0.999
MRS评分	0.244	0.183	1.779	0.182	1.276	0.892~1.827
甘油三酯	-0.353	0.408	0.746	0.388	0.703	0.316~1.565
低密度脂蛋白	-0.506	0.364	1.925	0.165	0.603	0.295~1.232

Fig. 1 ROC curve analysis of PFA-200 P2Y in predicting ischemic vascular events in patients receiving clopidogrel for prevention of ischemic stroke

References 24

[1]	Kang K, Park TH, Kim N, et al. Recurrent stroke, myocardial infarction, and major vascular events during the first year after acute ischemic stroke: The multicenter prospective observational study about recurrence and its determinants after acute ischemic stroke i[J]. J Stroke Cerebrovasc Dis, 2016, 25(3):656-664. doi: 10.1016/j.jstrokecerebrovasdis.2015.11.036 pmid: 26750575
[2]	Alhazzani A, Venkatachalapathy P, Padhilahouse S, et al. Biomarkers for antiplatelet therapies in acute ischemic stroke: A clinical review[J]. Front Neurol, 2021, 12:667234. doi: 10.3389/fneur.2021.667234 URL
[3]	Hidayat R, Nabilah RA, Rasyid A, et al. Clopidogrel resistance among ischemic stroke patients and its risk factors in indonesia[J]. Acta Med Acad, 2022, 51(1):29-34. doi: 10.5644/ama2006-124.367 pmid: 35695400
[4]	Mason GA, Rabbolini DJ. The current role of platelet function testing in clinical practice[J]. Semin Thromb Hemost, 2021, 47(7):843-854. doi: 10.1055/s-0041-1728786 pmid: 34130344
[5]	贾媛, 白世茹, 李如意, 等. 血小板功能检测的常用方法及容易忽略的影响因素[J]. 中国心血管杂志, 2020, 25(2):197-200.
[6]	Favaloro EJ. Clinical utility of closure times using the platelet function analyzer-100/200[J]. Am J Hematol, 2017, 92(4):398-404. doi: 10.1002/ajh.24620 pmid: 27935090
[7]	Yi X, Lin J, Zhou Q, et al. Clopidogrel resistance increases rate of recurrent stroke and other vascular events in chinese population[J]. J Stroke Cerebrovasc Dis, 2016, 25(5):1222-1228. doi: 10.1016/j.jstrokecerebrovasdis.2016.02.013 URL
[8]	Cayla G, Hulot J S, O'Connor SA, et al. Clinical, angiographic, and genetic factors associated with early coronary stent thrombosis[J]. JAMA, 2011, 306(16):1765-1774. doi: 10.1001/jama.2011.1529 pmid: 22028352
[9]	Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel[J]. N Engl J Med, 2009, 360(4):354-362. doi: 10.1056/NEJMoa0809171 URL
[10]	Collet JP, Hulot JS, Pena A, et al. Cytochrome p450 2c19 polymorphism in young patients treated with clopidogrel after myocardial infarction: A cohort study[J]. Lancet, 2009, 373(9660):309-317. doi: 10.1016/S0140-6736(08)61845-0 URL
[11]	Fu H, Hu P, Ma C, et al. Association of clopidogrel high on-treatment reactivity with clinical outcomes and gene polymorphism in acute ischemic stroke patients: An observational study[J]. Medicine (Baltimore), 2020, 99(15):e19472. doi: 10.1097/MD.0000000000019472 URL
[12]	Chetty M, Ravenstijn P, Manchandani P. Clopidogrel dosing: Current successes and emerging factors for further consideration[J]. Clin Pharmacol Ther, 2021, 109(5):1203-1211. doi: 10.1002/cpt.v109.5 URL
[13]	Kamarova M, Baig S, Patel H, et al. Antiplatelet use in ischemic stroke[J]. Ann Pharmacother, 2022, 56(10):1159-1173. doi: 10.1177/10600280211073009 URL
[14]	Zhou K, Yu S, Li J, et al. High on-treatment platelet reactivity is associated with poor outcomes after ischemic stroke: A meta-analysis[J]. Acta Neurol Scand, 2022, 146(3):205-224. doi: 10.1111/ane.13655 pmid: 35652290
[15]	Le Blanc J, Mullier F, Vayne C, et al. Advances in platelet function testing-light transmission aggregometry and beyond[J]. J Clin Med, 2020, 9(8):2636. doi: 10.3390/jcm9082636 URL
[16]	Hu YF, Lu TM, Wu CH, et al. Differences in high on-treatment platelet reactivity between intra-coronary and peripheral blood after dual anti-platelet agents in patients with coronary artery disease[J]. Thromb Haemost, 2013, 110(1):124-130. doi: 10.1160/TH13-01-0034 URL
[17]	Heireman L, Monteyne T, Hemelsoet D, et al. Search for a practical approach for detection of clopidogrel resistance: comparison of light transmission aggregometry and innovance(r) PFA P2Y cartridge and correlation with cyp2c19 variants[J]. Int J Lab Hematol, 2020, 42(4):e189-e191.
[18]	Tsantes A, Ikonomidis I, Papadakis I, et al. Evaluation of the role of the new innovance PFA P2Y test cartridge in detection of clopidogrel resistance[J]. Platelets, 2012, 23(6):481-489. doi: 10.3109/09537104.2012.689037 pmid: 22646492
[19]	Wisniewski A. Multifactorial background for a low biological response to antiplatelet agents used in stroke prevention[J]. Medicina (Kaunas), 2021, 57(1):59.
[20]	Li S, Choi JL, Guo LZ, et al. Correlation between the cyp2c19 phenotype status and the results of three different platelet function tests in cardiovascular disease patients receiving antiplatelet therapy: an emphasis on newly introduced platelet function analyzer-200 P2Y test[J]. Ann Lab Med, 2016, 36(1):42-48. doi: 10.3343/alm.2016.36.1.42 pmid: 26522758
[21]	Li S, Choi JL, Guo LZ, et al. Correlation between the cyp2c19 phenotype status and the results of three different platelet function tests in cardiovascular disease patients receiving antiplatelet therapy: An emphasis on newly introduced platelet function analyzer-200 p2y test[J]. Ann Lab Med, 2016, 36(1):42-48. doi: 10.3343/alm.2016.36.1.42 pmid: 26522758
[22]	Cheng Y, Shao T, Huang L, et al. Platelet function tests predicting the efficacy and safety of aspirin secondary prevention[J]. Neurol Res, 2022, 44(4):291-298. doi: 10.1080/01616412.2021.1981103 URL
[23]	Alkattan A, Alkhalifah A, Alsalameen E, et al. Polymorphisms of genes related to phase ii metabolism and resistance to clopidogrel[J]. Pharmacogenomics, 2022, 23(1):61-79. doi: 10.2217/pgs-2021-0092 URL
[24]	Akkaif MA, Daud N, Sha'Aban A, et al. The role of genetic polymorphism and other factors on clopidogrel resistance (CR) in an asian population with coronary heart disease (CHD)[J]. Molecules, 2021, 26(7):1987. doi: 10.3390/molecules26071987 URL