Journal of Neurology

, Volume 258, Issue 11, pp 1979–1986 | Cite as

Aspirin resistance in patients with acute ischemic stroke

  • Serkan Ozben
  • Beste Ozben
  • Azra Meryem Tanrikulu
  • Feriha Ozer
  • Tomris Ozben
Original Communication

Abstract

Aspirin is used in ischemic stroke therapy. However, some patients are not responsive to the antithrombotic action of aspirin. The aim of this study was to assess the prevalence of aspirin resistance in stroke patients and its association with mortality. One-hundred and six patients (mean age 64.9 ± 14.6 years, 53 male) with acute ischemic stroke were consecutively recruited. All subjects were taking aspirin regularly. Aspirin responsiveness was determined by Ultegra Rapid Platelet Function Assay-ASA (VerifyNow Aspirin). Aspirin resistance was defined as aspirin reaction unit (ARU) ≥ 550. Aspirin resistance was detected in 35 patients. There were not any significant differences in age, gender and comorbidities between aspirin-resistant and aspirin-sensitive patients. The mean National Institute of Health Stroke Scale (NIHSS) scores of the aspirin-resistant and aspirin-sensitive patients were 15 ± 3 and 12 ± 5, respectively (p = 0.006). Twenty-seven patients had a history of prior ischemic stroke and eight of them had aspirin resistance. Eleven patients died in-hospital and a total of 43 patients died during 2 years. Both the in-hospital and 2-year mortality rates were significantly higher in patients with aspirin resistance (20 vs. 5.6%, p = 0.038 and 60.0 vs. 31.0%, p = 0.004, respectively). Regression analysis revealed aspirin resistance [odds ratio (OR) 3.097, 95% confidence interval (CI) 1.070–8.959, p = 0.037] as an independent predictor of 2-year mortality, as well as age (OR 1.051, 95% CI 1.003–1.102, p = 0.038) and NIHSS scores (OR 1.208, 95% CI 1.016–1.437, p = 0.033). Aspirin resistance is not uncommon in patients with acute ischemic stroke and is associated with short and long term mortality in these patients.

Keywords

Acute stroke Aspirin Aspirin resistance Ischemic stroke Mortality Prognosis 

References

  1. 1.
    Feigin VL (2005) Stroke epidemiology in the developing world. Lancet 365:2160–2161PubMedCrossRefGoogle Scholar
  2. 2.
    Donnan GA, Fisher M, Macleod M, Davis SM (2008) Stroke. Lancet 371:1612–1623PubMedCrossRefGoogle Scholar
  3. 3.
    Bogousslavsky J, Van Melle G, Regli F (1988) The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke. Stroke 19:1083–1092PubMedCrossRefGoogle Scholar
  4. 4.
    Yip HK, Liou CW, Chang HW, Lan MY, Liu JS, Chen MC (2005) Link between platelet activity and outcomes after an ischemic stroke. Cerebrovasc Dis 20:120–128PubMedCrossRefGoogle Scholar
  5. 5.
    Antithrombotic Trialists’ Collaboration (2002) Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 324:71–86CrossRefGoogle Scholar
  6. 6.
    Ridker PM, Manson JE, Buring JE, Goldhaber SZ, Hennekens CH (1991) The effect of chronic platelet inhibition with low-dose aspirin on atherosclerotic progression and acute thrombosis: clinical evidence from the Physicians’ Health Study. Am Heart J 122:1588–1592PubMedCrossRefGoogle Scholar
  7. 7.
    ISIS-2 (Second International Study of Infarct Survival) Collaborative Group (1988) Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 2:349–360Google Scholar
  8. 8.
    Zimmermann N, Wenk A, Kim U, Kienzle P, Weber AA, Gams E, Schrör K, Hohlfeld T (2003) Functional and biochemical evaluation of platelet aspirin resistance after coronary artery bypass surgery. Circulation 108:542–547PubMedCrossRefGoogle Scholar
  9. 9.
    Borna C, Lazarowski E, van Heusden C, Ohlin H, Erlinge D (2005) Resistance to aspirin is increased by ST-elevation myocardial infarction and correlates with adenosine diphosphate levels. Thromb J 3:10PubMedCrossRefGoogle Scholar
  10. 10.
    Kahraman G, Sahin T, Kilic T, Baytugan NZ, Agacdiken A, Ural E, Ural D, Komsuoglu B (2007) The frequency of aspirin resistance and its risk factors in patients with metabolic syndrome. Int J Cardiol 115:391–396PubMedCrossRefGoogle Scholar
  11. 11.
    Watala C, Pluta J, Golanski J, Rozalski M, Czyz M, Trojanowski Z, Drzewoski J (2005) Increased protein glycation in diabetes mellitus is associated with decreased aspirin-mediated protein acetylation and reduced sensitivity of blood platelets to aspirin. J Mol Med 83:148–158PubMedCrossRefGoogle Scholar
  12. 12.
    Anfossi G, Russo I, Trovati M (2008) Resistance to aspirin and thienopyridines in diabetes mellitus and metabolic syndrome. Curr Vasc Pharmacol 6:313–328PubMedCrossRefGoogle Scholar
  13. 13.
    Fateh-Moghadam S, Plöckinger U, Cabeza N, Htun P, Reuter T, Ersel S, Gawaz M, Dietz R, Bocksch W (2005) Prevalence of aspirin resistance in patients with type 2 diabetes. Acta Diabetol 42:99–103PubMedCrossRefGoogle Scholar
  14. 14.
    Gorog DA, Sweeny JM, Fuster V (2009) Antiplatelet drug ‘resistance’. Part 2: laboratory resistance to antiplatelet drugs-fact or artifact? Nat Rev Cardiol 6:365–373PubMedGoogle Scholar
  15. 15.
    Eikelboom JW, Emery J, Hankey GJ (2010) The use of platelet function assays may help to determine appropriate antiplatelet treatment options in a patient with recurrent stroke on baby aspirin: against. Stroke 41:2398–2399PubMedCrossRefGoogle Scholar
  16. 16.
    Lev EI (2009) Aspirin resistance transient laboratory finding or important clinical entity? J Am Coll Cardiol 53:678–680PubMedCrossRefGoogle Scholar
  17. 17.
    Bennett D, Yan B, Macgregor L, Eccleston D, Davis SM (2008) A pilot study of resistance to aspirin in stroke patients. J Clin Neurosci 15:1204–1209PubMedCrossRefGoogle Scholar
  18. 18.
    Hohlfeld T, Weber AA, Junghans U, Schumacher M, Boucher M, Schrör K, Siebler M (2007) Variable platelet response to aspirin in patients with ischemic stroke. Cerebrovasc Dis 24:43–50PubMedCrossRefGoogle Scholar
  19. 19.
    Berrouschot J, Schwetlick B, von Twickel G, Fischer C, Uhlemann H, Siegemund T, Siegemund A, Roessler A (2006) Aspirin resistance in secondary stroke prevention. Acta Neurol Scand 113:31–35PubMedCrossRefGoogle Scholar
  20. 20.
    Chen WH, Lee PY, Ng W, Tse HF, Lau CP (2004) Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment. J Am Coll Cardiol 43:1122–1126PubMedCrossRefGoogle Scholar
  21. 21.
    Coleman JL, Wang JC, Simon DI (2004) Determination of ındividual response to aspirin therapy using the Accumetrics Ultegra RPFA-ASA System. Point of Care: J Near-Patient Test Technol 3:77–82CrossRefGoogle Scholar
  22. 22.
    Algra A, van Gijn J (1996) Aspirin at any dose above 30 mg offers only modest protection after cerebral ischaemia. J Neurol Neurosurg Psychiatry 60:197–199PubMedCrossRefGoogle Scholar
  23. 23.
    Lee SJ, Kim TH, Kim JG, Lee BR, Chun JU, Oh GS, Lee J (2007) The prevalence of aspirin resistance and related factors in patients with ischemic stroke using the Rapid Platelet Function Assay. Stroke 38:524 (abstract)Google Scholar
  24. 24.
    Grundmann K, Jaschonek K, Kleine B, Dichgans J, Topka H (2003) Aspirin non-responder status in patients with recurrent cerebral ischemic attacks. J Neurol 250:63–66PubMedCrossRefGoogle Scholar
  25. 25.
    Harrison P, Segal H, Blasbery K, Furtado C, Silver L, Rothwell PM (2005) Screening for aspirin responsiveness after transient ischemic attack and stroke: comparison of 2 point-of-care platelet function tests with optical aggregometry. Stroke 36:1001–1005PubMedCrossRefGoogle Scholar
  26. 26.
    Boncoraglio GB, Bodini A, Brambilla C, Corsini E, Carriero MR, Parati EA (2009) Aspirin resistance determined with PFA-100 does not predict new thrombotic events in patients with stable ischemic cerebrovascular disease. Clin Neurol Neurosurg 111:270–273PubMedCrossRefGoogle Scholar
  27. 27.
    Karepov V, Tolpina G, Kuliczkowski W, Serebruany V (2008) Plasma triglycerides as predictors of platelet responsiveness to aspirin in patients after first ischemic stroke. Cerebrovasc Dis 26:272–276PubMedCrossRefGoogle Scholar
  28. 28.
    Jeon SB, Song HS, Kim BJ, Kim HJ, Kang DW, Kim JS, Kwon SU (2010) Biochemical aspirin resistance and recurrent lesions in patients with acute ischemic stroke. Eur Neurol 64:51–57PubMedCrossRefGoogle Scholar
  29. 29.
    Englyst NA, Horsfield G, Kwan J, Byrne CD (2008) Aspirin resistance is more common in lacunar strokes than embolic strokes and is related to stroke severity. J Cereb Blood Flow Metab 28:1196–1203PubMedCrossRefGoogle Scholar
  30. 30.
    Gum PA, Kottke-Marchant K, Welsh PA, White J, Topol EJ (2003) A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 41:961–965PubMedCrossRefGoogle Scholar
  31. 31.
    Eikelboom JW, Hirsh J, Weitz JI, Johnston M, Yi Q, Yusuf S (2002) Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 105:1650–1655PubMedCrossRefGoogle Scholar
  32. 32.
    Mueller MR, Salat A, Stangl P, Murabito M, Pulaki S, Boehm D, Koppensteiner R, Ergun E, Mittlboeck M, Schreiner W, Losert U, Wolner E (1997) Variable platelet response to low-dose ASA and the risk of limb deterioration in patients submitted to peripheral arterial angioplasty. Thromb Haemost 78:1003–1007PubMedGoogle Scholar
  33. 33.
    Wang JC, Aucoin-Barry D, Manuelian D, Monbouquette R, Reisman M, Gray W, Block PC, Block EH, Ladenheim M, Simon DI (2003) Incidence of aspirin nonresponsiveness using the Ultegra Rapid Platelet Function Assay-ASA. Am J Cardiol 92:1492–1494PubMedCrossRefGoogle Scholar
  34. 34.
    Grotemeyer KH, Scharafinski HW, Husstedt IW (1993) Two-year follow-up of aspirin responder and aspirin non responder. A pilot-study including 180 post-stroke patients. Thromb Res 71:397–403PubMedCrossRefGoogle Scholar
  35. 35.
    Adams RJ, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R, Johnston SC, Katzan I, Kelly-Hayes M, Kenton EJ, Marks M, Sacco RL, Schwamm LH, American Heart Association, American Stroke Association (2008) Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke 39:1647–1652PubMedCrossRefGoogle Scholar
  36. 36.
    Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR (2008) Aspirin “resistance” and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ 336:195–198PubMedCrossRefGoogle Scholar
  37. 37.
    Zytkiewicz M, Giełwanowska L, Wojtasińska E, Psuja P, Zawilska K (2008) Resistance to acetylsalicylic acid in patients after ischemic stroke. Pol Arch Med Wewn 118:727–733PubMedGoogle Scholar
  38. 38.
    Geisler T, Gawaz M (2008) Resistance to antiplatelet substances—a real clinical problem. Herz 33:260–268PubMedCrossRefGoogle Scholar
  39. 39.
    Hankey GJ, Eikelboom JW (2004) Aspirin resistance. BMJ 328:477–479PubMedCrossRefGoogle Scholar
  40. 40.
    Peters RJ, Mehta SR, Fox KA, Zhao F, Lewis BS, Kopecky SL, Diaz R, Commerford PJ, Valentin V, Yusuf S, Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Trial Investigators (2003) Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation 108:1682–1687PubMedCrossRefGoogle Scholar
  41. 41.
    Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ, CHARISMA Investigators (2006) Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 354:1706–1717PubMedCrossRefGoogle Scholar
  42. 42.
    Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, Leys D, Matias-Guiu J, Rupprecht HJ, MATCH investigators (2004) Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 364:331–337PubMedCrossRefGoogle Scholar
  43. 43.
    Lee JH, Cha JK, Lee SJ, Ha SW, Kwon SU (2010) Addition of cilostazol reduces biological aspirin resistance in aspirin users with ischaemic stroke: a double-blind randomized clinical trial. Eur J Neurol 17:434–442PubMedCrossRefGoogle Scholar
  44. 44.
    McCabe DJ, Harrison P, Mackie IJ, Sidhu PS, Lawrie AS, Purdy G, Machin SJ, Brown MM (2005) Assessment of the antiplatelet effects of low to medium dose aspirin in the early and late phases after ischaemic stroke and TIA. Platelets 16:269–280PubMedCrossRefGoogle Scholar
  45. 45.
    Harrison P, Segal H, Silver L, Syed A, Cuthbertson FC, Rothwell PM (2008) Lack of reproducibility of assessment of aspirin responsiveness by optical aggregometry and two platelet function tests. Platelets 19:119–124PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Serkan Ozben
    • 1
  • Beste Ozben
    • 2
  • Azra Meryem Tanrikulu
    • 2
  • Feriha Ozer
    • 1
  • Tomris Ozben
    • 3
  1. 1.Department of NeurologyHaseki Educational and Research HospitalIstanbulTurkey
  2. 2.Department of CardiologyMarmara University Faculty of MedicineIstanbulTurkey
  3. 3.Department of BiochemistryAkdeniz University Faculty of MedicineAntalyaTurkey

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