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The role of aspirin resistance on outcome in patients with acute coronary syndrome and the effect of clopidogrel therapy in the prevention of major cardiovascular events

  • Clinical Trials and Thromboepidemiology
  • Published:
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Background: Aspirin resistance may increase up to more then threefold the risk of major cardiovascular events (MACE) in patients with stable coronary artery disease.

Aim:The aim of our study was to determine; the prevalence of aspirin resistance in patients with acute coronary syndromes, the role of aspirin resistance on outcome in the follow-up and the effect of clopidogrel therapy in the prevention of MACE in aspirin resistant subjects.

Material and methods: We detected the prevelance of aspirin resistance in 105 patients with acute coronary syndrome. Platelet functions were analyzed in Platelet Function Analyzer (PFA)-100 (Dade Behring, Germany) with collagen and/or epinephrine (Col/Epi) and collagen and/or ADP (Col/ADP) cartridges. Primary end points of the study were myocardial infarction, unstable angina, cardiac death.

Results: 19% (n = 20) of patients were aspirin resistant by PFA-100. In the follow-up, MACE occured in 9 patients (45%) with aspirin resistance and in 10 patients (11.7%) with aspirin sensitive platelet aggregation (p = 0.001). Multivariate analysis showed that aspirin resistance was an independant predictor of MACE. The prevalence of MACE in patients who were on clopidogrel treatment for 12 months were lower compared to those who were on a clopidogrel treatment for the first six months (p = 0.040).

Conclusions: We determined that the MACE risk in patients with acute coronary syndromes having detected aspirin resistance, was higher at statistically significant levels compared to patients having aspirin sensitive platelet aggregation. Our results showed that aspirin resistance, was an independant predictor of MACE in patients with acute coronary syndrome.

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  1. Ridker PM, Manson JE, Buring JE et al. (1991) The effect of chronic platelet inhibition with low dose aspirin on atherosclerotic progression and acute thrombosis: Clinical evidence from Physicians Health Study. Am Heart J 122:1588–1592

    Article  PubMed  CAS  Google Scholar 

  2. Antiplatelet Trialists’ Collaboration (1994) Collaborative overview of randomized trials of antiplatelet therapy I. Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 308:81–106

    Google Scholar 

  3. Gum PA, Kottke-Marchant K, Poggio ED et al. (2001) Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol 88(3):230–235

    Article  PubMed  CAS  Google Scholar 

  4. Cipollone F, Patrignani P, Greco A et al. (1997) Differential suppression of thromboxane biosynthesis by indobufen and aspirin in patients with unstable angina pectoris. Circulation 96:1109–1116

    PubMed  CAS  Google Scholar 

  5. Cipollone F, Prontera C, Pini B et al. (2001) Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability. Circulation 104:921–927

    PubMed  CAS  Google Scholar 

  6. Belton O, Byrne D, Kearney D et al. (2000) Cyclooxygenase-1 and -2-dependent prostacyclin formation in patients with atherosclerosis. Circulation 102:840–845

    PubMed  CAS  Google Scholar 

  7. Larsson PT, Wallen NH, Hjemdahl P (1994) Norepinephrine-induced human platelet activation in vivo is only partly counteracted by aspirin. Circulation 89:1951–1957

    PubMed  CAS  Google Scholar 

  8. Pamukcu B, Oflaz H, Acar RD, Umman S, Koylan N, Umman B, Nisanci Y (2005) The role of exercise on platelet aggregation in patients with stable coronary artery disease: exercise induces aspirin resistant platelet activation. J Thromb Thrombolysis 20:17–22

    Article  PubMed  Google Scholar 

  9. Davis JW, Hartman CR, Lewis HD et al. (1985) Cigarette smoking-induced enhancement of platelet function: lack of prevention by aspirin in men with coronary artery disease. J Lab Clin Med 105:479–483

    PubMed  CAS  Google Scholar 

  10. Santos MT, Valles J, Marcus AJ et al. (1991) Enhancement of platelet reactivity and modulation of eicosanoid production by intact erythrocytes. J Clin Invest 87:572–580

    Article  Google Scholar 

  11. Kawasaki T, Ozeki Y, Igawa T et al. (2000) Increased platelet sensitivity to collagen in individuals resistant to low-dose aspirin. Stroke 31:591–595

    PubMed  CAS  Google Scholar 

  12. Maalej N, Folts JD (1996) Increased shear stress overcomes the anti-thrombotic platelet inhibitory effect of aspirin in stenosed dog coronary arteries. Circulation 93:1201–1205

    PubMed  CAS  Google Scholar 

  13. Patrono C, FitzGerald GA (1997) Isoprostanes: potential markers of oxidant stress in atherothrombotic disease. Arterioscler Thromb Vasc Biol 17:2309–2315

    PubMed  CAS  Google Scholar 

  14. McKee SA, Sane DC, Deliargyris EN (2002) Aspirin resistance in cardiovascular disease: A review of prevalence, mechanisms, and clinical significance. Thromb Haemost 88:711–715

    PubMed  CAS  Google Scholar 

  15. Macchi L, Christiaens L, Brabant S et al. (2003) Resistance in vitro to low-dose aspirin is associated with platelet PlA1 (GP IIIa) polymorphism but not with C807T (GP Ia/Iı a) and C-5T Kozak (GP Ibα) polymorphisms. J Am Coll Cardiol 42:1115–1119

    Article  PubMed  CAS  Google Scholar 

  16. Pamukcu B, Oflaz H, Nisanci Y (2005) The role of platelet glycoprotein IIIa polymorphism in the high prevalence of in vitro aspirin resistance in patients with intracoronary stent restenosis. Am Heart J 149:675–680

    Article  PubMed  CAS  Google Scholar 

  17. Gum PA, Kottke-Marchant K, Welsh PA et al. (2003) A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 41:961–965

    Article  PubMed  CAS  Google Scholar 

  18. Favaloro EJ (2002) Clinical application of the PFA-100. Curr Opin Hematol 9:407–415

    Article  PubMed  Google Scholar 

  19. Mammen EF, Alsbameeri RS, Comp PC (1995) Preliminary data from a field trial of the PFA-100® system. Semin Thromb Hemost 21:113–121

    PubMed  Google Scholar 

  20. Mueller MR, Salat A, Stangl P et al. (1997) Variable platelet response to low-dose ASA and the risk of limb deterioration in patients submitted to peripheral arterial angioplasty. Thromb Haemost 78:1003–1007

    Google Scholar 

  21. Grotemeyer KH, Scharafinski HW, Husstedt IW et al. (1993) Two-Year follow-up of aspirin responder and aspirin non responder a pilot-study including 180 post-stroke patients. Thromb Research 71:397–403

    Article  CAS  Google Scholar 

  22. Grundmann K, Jaschonek K, Kleine B et al. (2003) Aspirin non-responder status in patients with recurrent cerebral ischemic attacks. J Neurol 250:63–66

    Article  PubMed  CAS  Google Scholar 

  23. CAPRIE Steering committee (1996) A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 348:1329–1339

    Article  Google Scholar 

  24. Mehta SR, Yusuf S, Peters RJ et al. (2001) Effects of pretreatment with clopidogrel and aspirin followed bu long-term therapy in patients undergoing percutaneous coronary intervention: The PCI-CURE study. Lancet 358:527–533.

    Google Scholar 

  25. The CREDO Investigators (2002) Clopidogrel for reduction of events during observation. JAMA 288:2411–2420

    Article  Google Scholar 

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Correspondence to Burak Pamukcu.

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Pamukcu, B., Oflaz, H., Oncul, A. et al. The role of aspirin resistance on outcome in patients with acute coronary syndrome and the effect of clopidogrel therapy in the prevention of major cardiovascular events. J Thromb Thrombolysis 22, 103–110 (2006).

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