Copyright © 2004 by the European Society of Cardiology.
Letter to the Editor
Do statins really interfere with clopidogrel-induced platelet function?: Reply
Cardiology Department, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791 Bochum, Germany
* Tel.: +49-234-509-2301; fax: +49-234-509-2353
E-mail address: horst.neubauer{at}ruhr-uni-bochum.de
Dr. Shechter correctly notes that there exist three different techniques to measure ex vivo the effects of clopidogrel on platelet activity, with the flow cytometry is probably the most sensitive method. Using aggregometry, Lau et al.1 observed a strong and dose-dependent interference between atorvastatin and the inhibitory effect of clopidogrel on platelet function. We measured instead platelet activation by flow cytometry,2 and observed only a marginal interference, predominantly in the loading phase, and to an even lesser extent in the maintenance phase after clopidogrel application. A recent study used 600 mg clopidogrel for loading, and did not observe a significant interference between various statins and clopidogrel on ADP-induced platelet aggregation.3
All studies used ex vivo platelet function tests and measured only indirectly the drug–drug interaction between lipophilic statins and conversion of the prodrug clopidogrel into an active metabolite. Certainly, this potential interference between statins and clopidogrel cannot directly be translated into clinical outcome. A retrospective analysis of clinical studies (MITRAplus registry,4 CREDO-study5) revealed no significant influence of different statins on the clinical outcome in clopidogrel treated patients. Thus, we agree to the suggestion of Dr. Shechter that large, well-designed and prospective trials may be helpful to further resolve this potential dilemma.
Perhaps more important as the potential interference between statins and clopidogrel may be the observation that a certain percentage of patients apparently does not respond at all to clopidogrel treatment.2,6 Others noted a pronounced variability in the effectiveness of clopidogrel.7 Prospective studies will also be helpful to further characterize these patients, and to re-define antithrombotic therapy for this subgroup.
Given the marginal interference in our study and the high variability, there is no need to discontinue the statin use during the clopidogrel treatment or to prefer hydrophylic statins in patients with clopidogrel comedication.
References
- Lau WC, Waskell LA, Watkins PB et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation. Circulation. 2003;107:32–37.
[Abstract/Free Full Text] - 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] - Muller I, Besta F, Schulz C et al. Effects of statins on platelet inhibition by a high loading dose of clopidogrel. Circulation 2003 Oct 20 [Epub ahead of print].
- Wienbergen H, Gitt AK, Schiele R et al. Comparison of clinical benefits of clopidogrel therapy in patients with acute coronary syndromes taking atorvastatin versus other statin therapies. Am. J. Cardiol. 2003;92:285–288.[CrossRef][ISI][Medline]
- Saw J, Steinhubl SR, Berger PB et al. Lack of adverse clopidogrel–atorvastatin clinical interaction from secondary analysis of a randomized, placebo-controlled clopidogrel trial. Circulation. 2003;108:921–924.
[Abstract/Free Full Text] - 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.[ISI][Medline]
- Gurbel PA, Bliden KP, Hiatt BL et al. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation. 2003;107:2908–2913.
[Abstract/Free Full Text]
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