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J Thorac Cardiovasc Surg 2005;129:1197
© 2005 The American Association for Thoracic Surgery

Letters to the Editor

Why clopidogrel failed to inhibit platelet function early after coronary artery bypass surgery: To load or not to load, and is it a question of resistance?

Ian Hunt, MRCSa, Lucy J.H. Blows, MRCPb, Sundip J. Patel, MRCPb

a Department of Cardiothoracic Surgery, St Thomas’ Hospital, London, United Kingdom
b Department of Cardiology, St Thomas’ Hospital, London, United Kingdom

To the Editor:

Antiplatelet therapy remains a topic of much-deserved attention and debate. We read with interest the recent article by Lim and associates1 in which they found that clopidogrel after coronary artery bypass grafting failed to inhibit platelet function, on the basis of the percentage platelet aggregation on day 5. Patients were randomized to receive 100 or 325 mg of aspirin daily or 75 mg of clopidogrel daily for 5 days after coronary artery bypass grafting. It is not clear whether patients in the clopidogrel arm received a loading dose before the daily maintenance dose. Several similar studies assessing platelet inhibition, albeit in the context of percutaneous coronary intervention, have demonstrated the importance of appropriate loading of 300 to 600 mg if steady-state levels of platelet aggregation are to be achieved within the first 24 hours.2–4 Daily maintenance dosing with 75 mg of clopidogrel without preloading, as in this study, has been shown to result in steady-state levels of platelet inhibition only after 3 to 7 days.5

The second observation with regard to this study is that the investigators did not state whether a baseline pretreatment sample was taken before surgery or before administration of the antiplatelet therapy. Whether this would have added much to the final analysis remains unclear, but evidence, again drawn from studies in the percutaneous coronary intervention setting, have suggested pretreatment platelet reactivity to be an important determinant of posttreatment reactivity.6

The final comment is the most elusive, namely, the issue of "clopidogrel resistance." Although it was not directly mentioned by the authors, we can assume that it was alluded to in their discussion. It is likely that a correlation exists between a laboratory measure of clinical clopidogrel nonresponsiveness and the clinical outcome. However, until such time as there is greater understanding of the likely mechanisms of clopidogrel responsiveness and the individual heterogeneity that is apparent, can we totally dismiss the efficacy of clopidogrel in the early postoperative period?

References

  1. Lim E, Cornelissen J, Routledge T, Kirtland S, Charman SC, Bellm S, et al. Clopidogrel did not inhibit platelet function early after coronary artery bypass surgery. a prospective randomized trial. J Thorac Cardiovasc Surg. 2004;128:432-435.[Abstract/Free Full Text]
  2. Petersen JL, Dery JP, Fischi MC, Hernandez AF, Hranitzky PM, Rao SV, et al. Highlights from the American College of Cardiology Annual Scientific Sessions 2003: March 28 to April 2, 2003. Am Heart J. 2003;146:19-26.[Medline]
  3. Assali AR, Salloum J, Sdringola S, Moustapha A, Ghani M, Hale S, et al. Effects of clopidogrel pretreatment before percutaneous coronary intervention in patients treated with glycoprotein IIb/IIIa inhibitors (abciximab or tirofiban). Am J Cardiol. 2001;88:884-886A6.[Medline]
  4. Chan AW, Moliterno DJ, Berger PB, Stone GW, DiBattiste PM, Yakubov SL, et al. Triple antiplatelet therapy during percutaneous coronary intervention is associated with improved outcomes including one-year survival. results from the Do Tirofiban and ReoProGive Similar Efficacy Outcome Trial (TARGET). J Am Coll Cardiol. 2003;42:1188-1195.[Abstract/Free Full Text]
  5. Savcic M, Hauert J, Bachmann F, Wyld PJ, Geudelin B, Cariou R. Clopidogrel loading dose regimens. kinetic profile of pharmacodynamic response in healthy subjects. Semin Thromb Hemost. 1999;25(suppl 2):15-19.[Medline]
  6. Gurbel PA, Bliden KP, Hiatt BL, O’Connor CM. Clopidogrel for coronary stenting. response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003;107:2908-2913.[Abstract/Free Full Text]




This Article
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Right arrow Author home page(s):
Ian Hunt
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Right arrow Articles by Patel, S. J.
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Related Collections
Right arrow Cardiac - pharmacology
Right arrow Cardiac - physiology
Right arrow Coronary disease

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