Skip to main content
SpringerLink
Log in

Antiplatelet resistance with aspirin and clopidogrel: Is it real and does it matter?

  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Platelets play a pivotal role in the pathophysiology of ischemic complications of atherosclerotic cardiovascular disease. Aspirin and clopidogrel are oral antiplatelet drugs that have been shown to reduce adverse clinical events across the wide spectrum of patients with atherothrombotic disease. However, recurrent ischemic events still occur in a significant proportion of patients despite treatment with these antiplatelet drugs. The concept of antiplatelet resistance therefore emerges. Although uniform definitions and standardized assays are not yet available, numerous studies have documented the interindividual variability in platelet responsiveness to oral antiplatelet drugs. Evidence is also accumulating to demonstrate that hyporesponsiveness to antiplatelet drugs in the laboratory (ie, resistance) is associated with adverse clinical events in different patient populations. Clinical application of antiplatelet resistance will require proof from prospective randomized trials that modifications of antiplatelet therapy based on tests of antiplatelet responsiveness will improve the outcomes of patients with antiplatelet resistance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Antithrombotic Trialists#x2019; 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.

  2. Barnathan ES, Schwartz JS, Taylor L, et al.: Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty. Circulation 1987, 76:125–134.

    PubMed  CAS  Google Scholar 

  3. Schwartz L, Bourassa MG, Lesperance J, et al.: Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty. N Engl J Med 1988, 318:1714–1719.

    Article  PubMed  CAS  Google Scholar 

  4. Lembo NJ, Black AJR, Roubin GS, et al.: Effect of pre-treatment with aspirin versus aspirin plus dipyridamole on frequency and type of acute complications of percutaneous transluminal coronary angioplasty. Am J Cardiol 1990, 65:422–426.

    Article  PubMed  CAS  Google Scholar 

  5. Patrono C, Bachmann F, Baigent C, et al.: Expert consensus document on the use of antiplatelet agents. The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology. Eur Heart J 2004, 25:166–181.

    Article  PubMed  Google Scholar 

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

  7. Yusuf S, Zhao F, Mehta SR, et al.: Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001, 345:494–502.

    Article  PubMed  CAS  Google Scholar 

  8. Steinhubl SR, Berger PB, Mann JT 3rd, et al.: Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002, 288:2411–2420.

    Article  PubMed  CAS  Google Scholar 

  9. Sabatine MS, Cannon CP, Gibson CM, et al.: Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005, 352:1179–1189.

    Article  PubMed  CAS  Google Scholar 

  10. Chen ZM, Pan HC, Chen YP, et al.: Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005, 366:1607–1621.

    Article  PubMed  CAS  Google Scholar 

  11. Mehta J, Mehta P, Burger C, Pepine CJ: Platelet aggregation studies in coronary artery disease. Part 4. Effect of aspirin. Atherosclerosis 1978, 31:169–175.

    Article  PubMed  CAS  Google Scholar 

  12. Grotemeyer KH: Effects of acetylsalicylic acid in stroke patients. Evidence of nonresponders in a subpopulation of treated patients. Thromb Res 1991, 63:587–593.

    Article  PubMed  CAS  Google Scholar 

  13. Pappas JM, Westengard JC, Bull BS: Population variability in the effect of aspirin on platelet function. Implications for clinical trials and therapy. Arch Pathol Lab Med 1994, 118:801–804.

    PubMed  CAS  Google Scholar 

  14. Buchanan MR, Brister SJ: Individual variation in the effects of ASA on platelet function: implications for the use of ASA clinically. Can J Cardiol 1995, 11:221–227.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  16. Hurlen M, Seljeflot I, Arnesen H: The effect of different antithrombotic regimens on platelet aggregation after myocardial infarction. Scand Cardiovasc J 1998, 32:233–237.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Andersen K, Hurlen M, Arnesen H, Seljeflot I: Aspirin nonresponsiveness as measured by PFA-100 in patients with coronary artery disease. Thromb Res 2002, 108:37–42.

    Article  PubMed  Google Scholar 

  19. Macchi L, Christiaens L, Brabant S, et al.: Resistance to aspirin in vitro is associated with increased platelet sensitivity to adenosine diphosphate. Thromb Res 2002, 107:45–49.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Wang JC, Aucoin-Barry D, Manuelian D, et al.: Incidence of aspirin nonresponsiveness using the Ultegra Rapid Platelet Function Assay-ASA. Am J Cardiol 2003, 92:1492–1494.

    Article  PubMed  Google Scholar 

  22. Lee PY, Chen WH, Ng W, et al.: Low-dose aspirin increases aspirin resistance in patients with coronary artery disease. Am J Med 2005, 118:723–727.

    Article  PubMed  CAS  Google Scholar 

  23. • McKee SA, Sane DC, Deliargyris EN: Aspirin resistance in cardiovascular disease: a review of prevalence, mechanisms, and clinical significance. Thromb Haemost 2002, 88:711–715.Informative review on the mechanisms of aspirin resistance

    PubMed  CAS  Google Scholar 

  24. Bhatt DL: Aspirin resistance: more than just a laboratory curiosity. J Am Coll Cardiol 2004, 43:1127–1129.

    Article  PubMed  Google Scholar 

  25. Grotemeyer KH, Scharafinski HW, Husstedt IW: Twoyear follow-up of aspirin responder and aspirin non-responder. A pilot study including 180 post-stroke patients. Thromb Res 1993, 71:397–403.

    Article  PubMed  CAS  Google Scholar 

  26. •• Eikelboom JW, Hirsh J, Weitz JI, et al.: Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002, 105:1650–1655.Influential paper describing the clinical risk associated with aspirin resistance that aroused widespread interest in this field

    Article  PubMed  CAS  Google Scholar 

  27. •• Gum PA, Kottke-Marchant K, Welsh PA, et al.: A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003, 41:961–965.First prospective study documenting adverse outcomes of aspirinresistant patients using gold standard platelet function test

    Article  PubMed  CAS  Google Scholar 

  28. • Chen WH, Lee PY, Ng W, et al.: Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment. J Am Coll Cardiol 2004, 43:1122–1126.Simple study revealing the importance of hyporesponsiveness to aspirin#x2019;s platelet antiaggregatory effect on myocardial necrosis after PCI

    Article  PubMed  CAS  Google Scholar 

  29. Chen WH, Lee PY, Ng W, et al.: Relation of aspirin resistance to coronary flow reserve in patients undergoing elective percutaneous coronary intervention. Am J Cardiol 2005, 96:760–763.

    Article  PubMed  CAS  Google Scholar 

  30. Jaremo P, Lindahl TL, Fransson SG, Richter A: Individual variations of platelet inhibition after loading doses of clopidogrel. J Intern Med 2002, 252:233–238.

    Article  PubMed  CAS  Google Scholar 

  31. Gurbel PA, Bliden KP: Durability of platelet inhibition by clopidogrel. Am J Cardiol 2003, 91:1123–1125.

    Article  PubMed  CAS  Google Scholar 

  32. Muller I, Besta F, Schulz C, et al.: Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost 2003, 89:783–787.

    PubMed  CAS  Google Scholar 

  33. Soffer D, Moussa I, Harjai KJ, et al.: Impact of angina class on inhibition of platelet aggregation following clopidogrel loading in patients undergoing coronary intervention: do we need more aggressive dosing regimens in unstable angina? Catheter Cardiovasc Interv 2003, 59:21–25.

    Article  PubMed  Google Scholar 

  34. Gurbel PA, Bliden KP, Hiatt BL, O#x2019;Connor CM: Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003, 107:2908–2913.

    Article  PubMed  Google Scholar 

  35. Mobley JE, Bresee SJ, Wortham DC, et al.: Frequency of nonresponse antiplatelet activity of clopidogrel during pretreatment for cardiac catheterization. Am J Cardiol 2004, 93:456–458.

    Article  PubMed  CAS  Google Scholar 

  36. Serebruany VL, Steinhubl SR, Berger PB, et al.: Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol 2005, 45:246–251.

    Article  PubMed  CAS  Google Scholar 

  37. Wiviott SD, Antman EM: Clopidogrel resistance: a new chapter in a fast-moving story. Circulation 2004, 109:3064–3067.

    Article  PubMed  Google Scholar 

  38. • Nguyen TA, Diodati JG, Pharand C: Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol 2005, 45:1157–1164.Comprehensive review on clopidogrel pharmacology and mechanisms of clopidogrel resistance

    Article  PubMed  CAS  Google Scholar 

  39. Barragan P, Bouvier JL, Roquebert PO, et al.: Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation. Catheter Cardiovasc Interv 2003, 59:295–302.

    Article  PubMed  Google Scholar 

  40. •• Matetzky S, Shenkman B, Guetta V, et al.: Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004, 109:3171–3175.Key prospective study illustrating clinical significance of clopidogrel resistance in a high-risk population

    Article  PubMed  CAS  Google Scholar 

  41. Lev EI, Patel RT, Maresh KJ, et al.: Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance. J Am Coll Cardiol 2006, 47:27–33.

    Article  PubMed  CAS  Google Scholar 

  42. Bhatt DL, Topol EJ: Clopidogrel added to aspirin versus aspirin alone in secondary prevention and high-risk primary prevention: rationale and design of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial. Am Heart J 2004, 148:263–268.

    Article  PubMed  CAS  Google Scholar 

  43. Pettersen AA, Seljeflot I, Abdelnoor M, Arnesen H: Unstable angina, stroke, myocardial infarction and death in aspirin non-responders. A prospective, randomized trial. The ASCET (ASpirin non-responsiveness and Clopidogrel Endpoint Trial) design. Scand Cardiovasc J 2004, 38:353–356.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, The University of Hong Kong Room 1929C, Block K, Queen Mary Hospital, Hong Kong, China

    Wai-Hong Chen MBBS

Authors
  1. Wai-Hong Chen MBBS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wai-Hong Chen MBBS.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, WH. Antiplatelet resistance with aspirin and clopidogrel: Is it real and does it matter?. Curr Cardiol Rep 8, 301–306 (2006). https://doi.org/10.1007/s11886-006-0063-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11886-006-0063-5

Keywords

Search

Navigation