Background: Stroke occurrence despite chronic antiplatelet drug (APD) treatment is frequent. We aimed at evaluating the relevance of platelet aggregation testing in the identification of stroke etiology in this context. Methods: Patients admitted for a suspected acute ischemic stroke, while under APD (aspirin and/or clopidogrel), were prospectively included. The efficacy of the APD was evaluated using a Multiplate™ assay. Resistance was confirmed using light transmission aggregometry. A standardized diagnostic work-up was performed to identify stroke mechanism according to the TOAST and the ASCO classifications. We evaluated the influence of APD functional status on stroke severity and identified potential determinants of resistance. Results: APD resistance was observed in 53 of the 287 patients (18.5%). No difference in stroke mechanism depending on APD efficacy was observed. Patients sensitive to APD had less severe initial stroke severity (mean National Institutes of Health Stroke Scale 3.9 ± 5.6 vs. 7.2 ± 6.8; p < 0.01). Main determinants for APD resistance were a worse control of the diabetes and higher baseline levels of inflammation (mean CRP 26.4 ± 56.0 vs. 9.3 ± 21.0; p < 0.01). Conclusions: Platelet function testing does not provide orientation concerning stroke mechanism in patients who were previously on APDs. However, the high frequency of APD resistance and its association with inflammation and stroke severity are confirmed.

1.
Grau AJ, Weimar C, Buggle F, et al: Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank. Stroke 2001;32:2559-2566.
2.
Grundmann K, Jaschonek K, Kleine B, Dichgans J, Topka H: Aspirin non-responder status in patients with recurrent cerebral ischemic attacks. J Neurol 2003;250:63-66.
3.
Hankey GJ, Eikelboom JW: Aspirin resistance. Lancet 2006;367:606-617.
4.
Snoep JD, Hovens MM, Eikenboom JC, van der Bom JG, Huisman MV: Association of laboratory-defined aspirin resistance with a higher risk of recurrent cardiovascular events: a systematic review and meta-analysis. Arch Intern Med 2007;167:1593-1599.
5.
Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR: Aspirin ‘resistance' and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ 2008;336:195-198.
6.
Englyst NA, Horsfield G, Kwan J, Byrne CD: Aspirin resistance is more common in lacunar strokes than embolic strokes and is related to stroke severity. J Cereb Blood Flow Metab 2008;28:1196-1203.
7.
Lai PT, Chen SY, Lee YS, Ho YP, Chiang YY, Hsu HY: Relationship between acute stroke outcome, aspirin resistance, and humoral factors. J Chin Med Assoc 2012;75:513-518.
8.
El-Mitwalli A, Azzam H, Abu-Hegazy M, Gomaa M, Wasel Y: Clinical and biochemical aspirin resistance in patients with recurrent cerebral ischemia. Clin Neurol Neurosurg 2013;115:944-947.
9.
Adams HP Jr, Bendixen BH, Kappelle LJ, et al: Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of org 10172 in acute stroke treatment. Stroke 1993;24:35-41.
10.
Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Hennerici MG: New approach to stroke subtyping: the A-S-C-O (phenotypic) classification of stroke. Cerebrovasc Dis 2009;27:502-508.
11.
Amarenco P, Bogousslavsky J, Caplan LR, Donnan GA, Wolf ME, Hennerici MG: The ASCOD phenotyping of ischemic stroke (updated ASCO phenotyping). Cerebrovasc Dis 2013;36:1-5.
12.
Amarenco P, Davis S, Jones EF, et al; Aortic Arch Related Cerebral Hazard Trial Investigators: Clopidogrel plus aspirin versus warfarin in patients with stroke and aortic arch plaques. Stroke 2014;45:1248-1257.
13.
Antithrombotic Trialists' Collaboration: Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86.
14.
Furie B, Furie BC: Mechanisms of thrombus formation. N Engl J Med 2008;359:938-949.
15.
Joseph R, Han E, Tsering C, Grunfeld S, Welch KM: Platelet activity and stroke severity. J Neurol Sci 1992;108:1-6.
16.
Zheng AS, Churilov L, Colley RE, Goh C, Davis SM, Yan B: Association of aspirin resistance with increased stroke severity and infarct size. JAMA Neurol 2013;70:208-213.
17.
Legrand V, Cuisset T, Chenu P, et al: Platelet reactivity and cardiovascular events after percutaneous coronary intervention in patients with stable coronary artery disease: the stent thrombosis in Belgium (STIB) trial. Euro Intervention 2014;10:204-211.
18.
Fong J, Cheng-Ching E, Hussain MS, Katzan I, Gupta R: Predictors of biochemical aspirin and clopidogrel resistance in patients with ischemic stroke. J Stroke Cerebrovasc Dis 2011;20:227-230.
19.
Bonello L, Tantry US, Marcucci R, et al; Working Group on High On-Treatment Platelet Reactivity: Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010;56:919-933.
20.
Mannu GS, Macartney A, Lambert JR, et al: The clinical utility of multiplate analyser measurement in platelet function testing following stroke and transient ischaemic attack. Eur J Haematol 2015;94:138-144.
21.
Sibbing D, Braun S, Morath T, et al: Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol 2009;53:849-856.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.