Platelet Function Testing for Aspirin Resistance Is Reasonable to Do
2010; Lippincott Williams & Wilkins; Volume: 41; Issue: 10 Linguagem: Inglês
10.1161/strokeaha.110.595637
ISSN1524-4628
Autores Tópico(s)Atrial Fibrillation Management and Outcomes
ResumoHomeStrokeVol. 41, No. 10Platelet Function Testing for Aspirin Resistance Is Reasonable to Do Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBPlatelet Function Testing for Aspirin Resistance Is Reasonable to DoYes! Mark J. Alberts, MD Mark J. AlbertsMark J. Alberts From the Department of Neurology, Northwestern University Feinberg School of Medicine, and the Stroke Program, Northwestern Memorial Hospital, Chicago, Ill. Originally published19 Aug 2010https://doi.org/10.1161/STROKEAHA.110.595637Stroke. 2010;41:2400–2401Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: August 19, 2010: Previous Version 1 When discussing the issue of aspirin resistance and platelet function testing, there are a number of data-based conclusions that I believe we can agree on:(1) Aspirin resistance is a real phenomenon. There are dozens of studies and a number of meta-analyses that show on average 15% to 25% of individuals will be aspirin-resistant (ie, lack of the anticipated antiplatelet response when taking aspirin).1,2 The largest meta-analysis included 42 studies and reported a 27% rate of aspirin resistance.3 Rates may be slightly higher in patients with stroke.4,5 The rate of aspirin resistance tends to increase with lower doses of aspirin and may be higher when using enteric-coated aspirin.3,4 The rate of aspirin resistance appears to increase with age above the mid-60s.1 Perhaps this relates to gastrointestinal issues such as stomach pH, which increases with age due to lower acid production.(2) Aspirin resistance has clinical consequences. Various studies, most in cardiac patients, have shown that individuals with aspirin resistance have an increased risk of having a cardiovascular event (stroke, myocardial infarction, vascular death) when followed for 2 to 5 years.6 A recent meta-analysis of 20 studies with >2900 patients reported that individuals with aspirin resistance had a significantly increased risk (3.85 OR) of having a cardiovascular event.7 Compliance with aspirin therapy was confirmed in 14 studies, and the dose of aspirin varied from 75 mg/day to 325 mg/day.Given these data and conclusions, there are several controversial points to consider:(1) What is the optimal method to determine aspirin resistance? This is 1 of the most common limitations mentioned in research on this topic. Different techniques for measuring aspirin resistance can produce somewhat different results. Assays using arachidonic acid as the agonist with just platelets report lower rates of aspirin resistance, typically approximately 5%. Tests using whole blood assays and point-of-care testing paradigms report higher rates ranging from 15% to 40%.2,8This variance is true of most tests of coagulation functions. However, this variation does not negate the concept of aspirin resistance or its clinical implications. Like with other tests, what is required is some consensus on a testing paradigm and normal ranges.Another misconception is that aspirin resistance is an all-or-nothing phenomenon. Like with most biological systems, the antiaggregation response to aspirin is almost certainly a continuum with lower responses associated with a higher risk of ischemic events, whereas higher responses may increase the risk of a hemorrhagic event.(2) Can aspirin resistance be overcome and thereby reduce the rate of ischemic events? In some studies, increasing the dose of aspirin can reduce the overall rate of aspirin resistance, although at least 5% to 10% of patients do not appear to have a significant response to aspirin at any reasonable dose. We have found that adding clopidogrel to aspirin can reduce the overall rate of aspirin resistance, although some patients fail to respond to even combination therapy.4 Genetic and metabolic factors may cause some cases of aspirin resistance.Increasing the dose of aspirin carries some risks and some unknowns. Higher doses of aspirin can increase the risk of gastrointestinal hemorrhage and other side effects. At higher doses, aspirin may inhibit the activity of the cyclo-oxygenase-2 enzyme, which produces prostacyclin, a potent endogenous antiplatelet compound and vasodilator. Like with any biological system, there must be a balance between too little and too much of any effect.(3) Can changing the dose of aspirin to achieve and maintain an effective level of antiplatelet activity result in a reduction in ischemic events without excess bleeding? This is the "Holy Grail" of this line of research. It is a very relevant issue for several reasons: (1) approximately 35% to 40% of patients with stroke are taking aspirin at the time of their event; and (2) in much of the world, aspirin is the only antiplatelet agent that is readily available and affordable. Therefore, there are important public health implications for being able to optimize the efficacy and safety of aspirin.Some have observed that clinical trials of aspirin have failed to demonstrate enhanced efficacy with higher doses; therefore, checking platelet function is likely to be irrelevant. Such statements are based largely on indirect comparisons of diverse studies; such comparisons are typically erroneous or misleading. In the ATC meta-analysis, the few studies that directly compared high-dose versus low-dose aspirin did show evidence of enhanced efficacy with higher doses, although the small number of outcome events limits firm conclusions.In summary, aspirin resistance is common and carries significant clinical consequences. Although we cannot prove that altering therapy in affected patients would reduce the risk of ischemic events, it seems reasonable to perform studies to determine the wisdom of such an approach. Would you want to take a medication that is not working as intended?The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. This article is Part 3 in a 3-part series. Parts 1 and 2 appear on pages 2396 and 2398, respectively.DisclosuresM.J.A. has received modest funding from Accumetrics for consulting work and speaking engagements related to platelet function testing.FootnotesCorrespondence to Mark J. Alberts, MD, 710 N Lake Shore Drive, Room 1420, Chicago, IL 60611. E-mail [email protected]References1 Shen H, Herzog W, Drolet M, Pakyz R, Newcomer S, Sack P, Karon H, Ryan KA, Zhao Y, Shi X, Mitchell BD, Shuldiner AR. Aspirin resistance in healthy drug-naive men versus women (from the Heredity and Phenotype Intervention Heart Study). Am J Cardiol. 2009; 104: 606–612.CrossrefMedlineGoogle Scholar2 Mansour K, Taher AT, Musallam KM, Alam S. Aspirin resistance. Adv Hematol. 2009; 2009: 937352.CrossrefMedlineGoogle Scholar3 Hovens MM, Snoep JD, Eikelboom JW. Prevalence of persistent platelet reactivity despite use of aspirin: a systemic review. Am Heart J. 2007; 153: 175–181.CrossrefMedlineGoogle Scholar4 Alberts MJ, Bergman DL, Molner E, Jovanovic BD, Ushiwata I, Teruya J. Antiplatelet effect of aspirin in patients with cerebrovascular disease. Stroke. 2004; 35: 175–178.LinkGoogle Scholar5 Bennett D, Yan B, Macgregor L, Eccleston D, Davis SM. A pilot study of resistance to aspirin in stroke patients. J Clin Neurosci. 2008; 15: 1204–1209.CrossrefMedlineGoogle Scholar6 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.CrossrefMedlineGoogle Scholar7 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.CrossrefMedlineGoogle Scholar8 Pamukcu B. A review of aspirin resistance; definition, possible mechanisms, detection with platelet function tests, and its clinical outcomes. J Thromb Thrombolysis. 2007; 23: 213–222.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Venketasubramanian N, Agustin S, Padilla J, Yumul M, Sum C, Lee S, Ponnudurai K and Gan R (2022) Comparison of Different Laboratory Tests to Identify "Aspirin Resistance" and Risk of Vascular Events among Ischaemic Stroke Patients: A Double-Blind Study, Journal of Cardiovascular Development and Disease, 10.3390/jcdd9050156, 9:5, (156) Javalkar V, Kuybu O, Amireh A and Kelley R (2020) Evolving Approaches to Antithrombotics in Stroke Prevention and Treatment, Southern Medical Journal, 10.14423/SMJ.0000000000001173, 113:11, (585-592), Online publication date: 1-Nov-2020. Pratiwi B, Setiasih S, Handayani S and Hudiyono S (2020) Dissolution study of bromelain resulting from partial purification of pineapple stem (Ananas comosus [L.] Merr) encapsulated in chitosan-guar gum and its activity as an antiplatelet THE 8TH INTERNATIONAL CONFERENCE OF THE INDONESIAN CHEMICAL SOCIETY (ICICS) 2019, 10.1063/5.0001347, , (030018) Diz-Küçükkaya R and López J (2018) Acquired Disorders of Platelet Function Hematology, 10.1016/B978-0-323-35762-3.00130-X, (1932-1943.e6), . Harrigan M and Deveikis J (2018) General Considerations for Neurointerventional Procedures Handbook of Cerebrovascular Disease and Neurointerventional Technique, 10.1007/978-3-319-66779-9_4, (167-246), . Yi X, Lin J, Wang C, Huang R, Han Z and Li J (2017) Platelet function-guided modification in antiplatelet therapy after acute ischemic stroke is associated with clinical outcomes in patients with aspirin nonresponse, Oncotarget, 10.18632/oncotarget.22293, 8:63, (106258-106269), Online publication date: 5-Dec-2017. Rosafio F, Lelli N, Mimmi S, Vandelli L, Bigliardi G, Dell'Acqua M, Picchetto L, Pentore R, Ferraro D, Trenti T, Nichelli P and Zini A (2017) Platelet Function Testing in Patients with Acute Ischemic Stroke: An Observational Study, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2017.04.023, 26:8, (1864-1873), Online publication date: 1-Aug-2017. Derle E, Öcal R, Kibaroğlu S, Çelikkol C, Bayraktar N, Verdi H, Ataç B and Can U (2016) Aspirin resistance in cerebrovascular disease and the role of glycoprotein IIIa polymorphism in Turkish stroke patients, Blood Coagulation & Fibrinolysis, 10.1097/MBC.0000000000000404, 27:2, (169-175), Online publication date: 1-Mar-2016. Kim J, Heo S, Choi K, Nam T, Choi S, Lee S, Park M, Kim B, Kim M, Saver J and Cho K (2015) Clinical Implications of Changes in Individual Platelet Reactivity to Aspirin Over Time in Acute Ischemic Stroke, Stroke, 46:9, (2534-2540), Online publication date: 1-Sep-2015. Achterberg S, Kappelle L, de Bakker P, Traylor M, Algra A and Minnerup J (2015) No Additional Prognostic Value of Genetic Information in the Prediction of Vascular Events after Cerebral Ischemia of Arterial Origin: The PROMISe Study, PLOS ONE, 10.1371/journal.pone.0119203, 10:4, (e0119203) Lago A, Parkhutik V, Tembl J, Vallés J, Santos M and Moscardó A (2014) Assessment of Platelet Function in Acute Ischemic Stroke Patients Previously Treated with Aspirin, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2014.07.007, 23:10, (2794-2799), Online publication date: 1-Nov-2014. Castilla-Guerra L, Navas-Alcántara M and Fernández-Moreno M (2014) Aspirin resistant patients with recent ischemic stroke, Revista Clínica Española (English Edition), 10.1016/j.rceng.2013.12.002, 214:3, (145-149), Online publication date: 1-Apr-2014. Castilla-Guerra L, Navas-Alcántara M and Fernández-Moreno M (2014) Resistencia a la aspirina en paciente con ictus isquémico reciente, Revista Clínica Española, 10.1016/j.rce.2013.10.003, 214:3, (145-149), Online publication date: 1-Apr-2014. Liu A, Li H, Li J, Wang Y, Chen D, Wang Y and Zheng G (2014) Chinese Herbal Medicine for Aspirin Resistance: A Systematic Review of Randomized Controlled Trials, Evidence-Based Complementary and Alternative Medicine, 10.1155/2014/890950, 2014, (1-16), . Gorelick P and Farooq M (2013) Advances in Our Understanding of "Resistance" to Antiplatelet Agents for Prevention of Ischemic Stroke, Stroke Research and Treatment, 10.1155/2013/727842, 2013, (1-7), . Harrigan M and Deveikis J (2013) General Considerations for Neurointerventional Procedures Handbook of Cerebrovascular Disease and Neurointerventional Technique, 10.1007/978-1-61779-946-4_4, (153-185), . Lai P, Chen S, Lee Y, Ho Y, Chiang Y and Hsu H (2012) Relationship between acute stroke outcome, aspirin resistance, and humoral factors, Journal of the Chinese Medical Association, 10.1016/j.jcma.2012.07.005, 75:10, (513-518), Online publication date: 1-Oct-2012. Meves S, Overbeck U, Endres H, Krogias C and Neubauer H (2017) Dose-dependent effect of early antiplatelet therapy in acute ischaemic stroke, Thrombosis and Haemostasis, 10.1160/TH11-06-0436, 107:01, (69-79), . Weber R, Brenck J and Diener H (2012) Antiplatelet Therapy in Cerebrovascular Disorders Antiplatelet Agents, 10.1007/978-3-642-29423-5_21, (519-546), . Lutsep H (2014) Update on selecting and adjusting antiplatelet therapy for prevention of noncardiogenic, recurrent ischemic stroke, Expert Review of Cardiovascular Therapy, 10.1586/erc.11.113, 9:10, (1295-1303), Online publication date: 1-Oct-2011. Feher A, Pusch G, Harang G, Gasztonyi B, Papp E, Werling D, Menyhart M, Komaromy H, Szapary L and Feher G (2011) Aspirin resistance in cerebrovascular patients, International Journal of Cardiology, 10.1016/j.ijcard.2011.07.028, 152:1, (111-112), Online publication date: 1-Oct-2011. De Boni A, De Riva V, Galloni E and Perini F (2011) Attività piastrinica residua e fallimento clinico della profilassi antitrombotica nell'attacco ischemico cerebrale acutoResidual platelet activity and clinical failure of antithrombotic prophylaxis in acute cerebral ischaemic stroke, La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine, 10.1007/s13631-011-0024-8, 7:3, (163-169), Online publication date: 1-Sep-2011. Topçuoglu M, Arsava E and Ay H (2014) Antiplatelet resistance in stroke, Expert Review of Neurotherapeutics, 10.1586/ern.10.203, 11:2, (251-263), Online publication date: 1-Feb-2011. October 2010Vol 41, Issue 10 Advertisement Article InformationMetrics https://doi.org/10.1161/STROKEAHA.110.595637PMID: 20724707 Manuscript receivedJuly 8, 2010Manuscript acceptedJuly 9, 2010Originally publishedAugust 19, 2010 Keywordsantiplatelet drugsantiplatelet RXaspirinPDF download Advertisement
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