Copyright © 2004 by the European Society of Cardiology.
Letters to the Editor
Do statins really interfere with clopidogrel-induced platelet function?
Sheba Medical Center, Heart Institute, Tel Aviv University, Tel Hashomer 52621, Israel
* Tel.: +972-3-5302645; fax: +972-3-6780581
E-mail address: shechtes{at}netviion.net.il
To the Editor
Following Lau et al.1 publication last year, suggesting that lipophilic statins may inhibit clopidogrel-induced platelet function, the medical community is torn apart between implementing the guidelines and prescribing statins to patients with coronary artery disease (CAD) undergoing percutaneous coronary interventions to further reducing mortality and morbidity and the possibility of harm, although not yet proven, by increasing platelet activity when statins are coadministered with clopidogerel.
Neubauer et al.2 recently contributed this uncertainty and dilemma. In a well-designed study they demonstrated that lipophilic statins (atorvastatin and simvastatin) reduced significantly the inhibitory effects of clopidogrel, especially during the loading phase, measured by flow-cytometry P-selectin (CD62P) activity.
Platelet activity is measured by the combination of the following three tests: (a) platelet aggregation by ADP or collagen-induced whole blood (or platelet-rich plasma) platelet aggregometry; (b) platelet adhesion by ex vivo perfusion (Badimon) chamber;3 and (c) platelet activation by flow-cytometry measurement of the surface membrane expression of CD62P (P-selectin, GMP140) in the whole blood.4–6 All three tests together are needed to test platelet function.
Lau and Neubauer based their conclusions on one test only out of the above three tests: Lau et al. studied only the in vitro anti-aggregation effect of clopidogrel in patients after stent deployment1 and Neubauer et al. only the flow-cytometry P-selectin (CD62P) activity.2 Blocking only one pathway does not necessarily predict stent restenosis (and/or in-stent thrombosis) and/or a worse clinical outcome.7 The medical community urgently needs a large, well-designed prospective trial, using the three tests – all together – as surrogate end-point for platelet function in order to conclude this dilemma and better guide our daily practice. Until then, physicians are urged to continue implement the guidelines and prescribe statins to CAD patients with or without clopidogrel coadministration.
References
- Lau WC, Waskell LA, Watkins PB et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation. Circulation. 2002;107:32–37.
- Neubauer H, Gunesdogan B, Hanefeld C et al. Lipophilic statins interfere with the inhibitory effects of clopidogrel on platelet function – a flow cytometry study. Eur. Heart J. 2003;24:1744–1749.
[Abstract/Free Full Text] - Badimon L, Badimon JJ, Galvez A et al. Influence of arterial damage and wall shear rate on platelet formation: ex vivo study in a swine model. Arteriosclerosis. 1986;6:312–320.
[Abstract/Free Full Text] - Janes SL, Wilson DJ, Chronos N et al. Evaluation of whole blood flow cytometric detection of platelet bound fibrinogen in normal subjects and patients with activated platelets. Thromb. Haemost. 1993;70:659–666.[Web of Science][Medline]
- Schafer Al. Antiplatelet activity. Am J. Med. 1996;101:199–209.[CrossRef][Web of Science][Medline]
- Rupprecht HJ, Darus H, Borkowski U et al. Comparison of antiplatelet effects of aspirin, ticlopidine, or their combination after stent implantation. Circulation. 1998;97:1046–1052.
[Abstract/Free Full Text] - Shechter M. Atorvastatin and the ability of clopidogrel to inhibit platelet aggregation. Circulation. 2003;107:210e.
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