Determination of the Prevalence of Aspirin and Clopidogrel Resistances in Patients with Coronary Artery Disease by using Various Platelet-function Tests

Kwang-Sook Woo; Bo-Ram Kim; Ji-Eun Kim; Ri-Young Goh; Long-Hao Yu; Moo-Hyun Kim; Jin-Yeong Han

doi:10.3343/kjlm.2010.30.5.460

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Woo, Kim, Kim, Goh, Yu, Kim, and Han: Determination of the Prevalence of Aspirin and Clopidogrel Resistances in Patients with Coronary Artery Disease by using Various Platelet-function Tests

Original Article

Korean J Leg Med 2010;30(5):460-468.

Published online: 14 January 2010

DOI: https://doi.org/10.3343/kjlm.2010.30.5.460

Determination of the Prevalence of Aspirin and Clopidogrel Resistances in Patients with Coronary Artery Disease by using Various Platelet-function Tests

Kwang-Sook Woo, M.D.¹, Bo-Ram Kim, M.D.¹, Ji-Eun Kim, M.D.¹, Ri-Young Goh, Ph.D.¹, Long-Hao Yu, M.D.², Moo-Hyun Kim, M.D.², Jin-Yeong Han, M.D.^1,³

¹Departments of Laboratory Medicine and Cardiology, Korea

²Dong-A University College of Medicine, Medical Research Center for Cancer Molecular Therapy, Korea

³Dong-A University, Busan, Korea

Corresponding author: Jin-Yeong Han, M.D. Department of Laboratory Medicine, Dong-A University College of Medicine, 1 Dongdaesin-dong 3-ga, Seo-gu, Busan 602-715, Korea Tel: +82-51-240-5323, Fax: +82-51-255-9366 E-mail: jyhan@dau.ac.kr

^∗ This study was supported by a Korea Science and Engineering Foundation (KOSEF) grant of the Korea government (MEST) (R13-2002-044-05002-0).

^∗ It is commonly accepted that a correlation coefficient (R) between 0 and 0.2 shows no correlation; between 0.2 and 0.4, low correlation; between 0.4 and 0.6, moderate correlation; between 0.6 and 0.8, high correlation; and values greater than 0.8, good correlation.

Revised 15 April 201012 August 2010 Accepted 18 August 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

Dual therapy with aspirin and clopidogrel has emerged as the gold standard therapy for patients treated with drug-eluting stents (DES). However, there is variability in patients' responses to this antiplatelet therapy, and some patients continue to show ischemic recurrences after therapy. The purpose of the study was to compare the simultaneously obtained results of various plateletfunction tests for assessing the prevalence of antiplatelet resistance in coronary artery disease patients undergoing DES therapy.

Methods:

A total of 66 patients were administered a loading dose of aspirin, clopidogrel, and cilostazol at least 12 hr before stenting. The results of VerifyNow (Accumetrics, USA), multiplate analyzer (Dynabyte Medical, Germany), and vasodilator-stimulated phosphoprotein/P2Y12 (Biocytex, France) assays were compared with those of light transmission aggregometry (LTA) analysis.

Results:

The P2Y12 reaction units and P2Y12% inhibition values obtained using the VerifyNow assay showed strong correlation (r) with the results of the LTA analysis. All tests results showed low concordance in defining the antiplatelet resistance in patients, and the degrees of agreement were as follows: 0 for aspirin reaction units; 0.25, P2Y12% inhibition; 0, aspirin-sensitive patients' identification test; 0.21, ADPtest; and 0.14, platelet reactivity index, expressed as the κ statistics. The prevalence of aspirin and clopidogrel resistances in patients resulted in remarkable variations, from 0% to 22.7% and from 9.1% to 48.5%, respectively.

Conclusions:

The clinical usefulness of the different assays for the correct classification of patients in terms of antiplatelet resistance remains unclear. Further studies are required to determine the best method for correlating the occurrences of adverse ischemic events.

Keywords: Aspirin, Clopidogrel, Resistance, Platelet-function tests

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Fig. 1.

Distribution of platelet aggregation results of various platelet-function tests and correlations between the results obtained from the various platelet-function tests and those of LTA analysis. (A) Platelet aggregation measured by LTA analysis. (B) ARU value measured by VerifyNow assay and its comparison with the result of LTA analysis performed using AA as the agonist. (C) PRU measured by using VerifyNow and its comparison with the result of LTA analysis performed using ADP as the agonist. (D) P2Y12% inhibition measured by using VerifyNow and its comparison with the result of the LTA analysis performed using ADP as the agonist. (E) ASPItest performed using multiplate analyzer and its comparison with the LTA analysis performed using AA as the agonist. (F) ADPtest performed using multiplate analyzer and its comparison with LTA analysis performed using ADP as the agonist. (G) PRI measured by using VASP/P2Y12 assay and its comparison with the result of the LTA analysis performed using ADP as the agonist.

Abbreviations: LTA, light transmission aggregometry; ARU, aspirin reaction units; AA, arachidonic acid; PRU, P2Y12 reaction units; VASP, vasodilator-stimulated phosphoprotein; ASPI, aspirin-sensitive patients identification.

Table 1.

Demographic and angiographic data of the patients with CAD (N=66)

Variable	N of patients (N=66)
Sex (female/male)	29/37
Age (yr)∗	63.0±10.9
BMI (kg/m²)∗	24.7±2.9
Risk factor^†
Active smoking	25 (37.8)
Diabetes mellitus	27 (40.9)
Hypertension	38 (27.6)
Hyperlipidemia	14 (21.2)
Angiographic diagnosis^†
1-VD	22 (33.3)
2-VD	26 (39.4)
3-VD	18 (27.3)
Clinical diagnosis^†
Stable angina	8 (12.1)
Unstable angina	40 (60.6)
AMI	18 (27.3)

^∗ Values are expressed as mean±SD;

^† Values are expressed as numbers (%).

Abbreviations: CAD, coronary artery disease; BMI, body mass index; VD, vessel disease; AMI, acute myocardial infarction

Table 2.

Prevalence of aspirin and clopidogrel resistance determined using various platelet-function tests

Variable	Prevalence (%)
Variable	Aspirin resistance	Clopidogrel resistance
LTA analysis	0 (0)	6 (9.1)
VerifyNow assay	2 (3.0)	28 (42.4)
Multiplate analyzer assay	15 (22.7)	14 (21.2)
VASP/P2Y12 assay	-	32 (48.5)

^∗ Values are expressed as numbers (%).

Abbreviations: LTA, light transmission aggregometry; VASP, vasodilator-stimulated phosphoprotein.

Table 3.

Degree of agreement on aspirin and clopidogrel resistance status between LTA analysis and other platelet-function tests∗

Variable	κ statistic
VerifyNow
ARU value	0
P2Y12% inhibition value	0.25
Multiplate analyzer
ASPItest	0
ADPtest	0.21
VASP/P2Y12 assay
PRI	0.14

^∗ Values are expressed in terms of κ statistic, and it is commonly accepted that a κ statistic between 0 and 0.2 indicates slight agreement; between 0.2 and 0.4, fair agreement; between 0.4 and 0.6, moderate agreement; 0.6 and 0.8, substantial agreement; and 0.8 and 1, almost perfect agreement.

Abbreviations: LTA, light transmission aggregometry; ARU, aspirin reaction units; ASPI, aspirin-sensitive patients identification; VASP, vasodilator-stimulated phosphoprotein; PRI, platelet reactivity index.

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