European Heart Journal Advance Access originally published online on December 16, 2007
European Heart Journal 2008 29(3):424; doi:10.1093/eurheartj/ehm552
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A double blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days: reply
Deutsches Herzzentrum München
Lazarettstr. 36
80636 München
Germany
Tel: + 49 89 1218 4073
Fax: + 49 89 1218 4013
Email: beckerath{at}dhm.mhn.de
Deutsches Herzzentrum München
Lazarettstr. 36
80636 München
Germany
Deutsches Herzzentrum München
Lazarettstr. 36
80636 München
Germany
We thank Zhang and Balavenkatesh for their valuable comments on our paper.1 We agree with them that maximal ADP-induced platelet aggregation was quite high in our recent double-blind randomized study in which we compared the antiplatelet effects of a 150 with a 75 mg daily clopidogrel maintenance dose. Although, light transmission aggregometry (LTA) is the gold standard to evaluate platelet function in response to agonists such as ADP, it is a poorly standardized method2 which makes it nearly impossible to compare absolute values obtained in different laboratories. Importantly, during the period of this double-blind randomized study, LTA was uniformly performed on a Chrono-log aggregometer as described in the methods section.1 Therefore, we believe that we describe an existing dose–response phenomenon. This is supported by the data that we obtained with the VerifyNowTM P2Y12 assay. These data also show that the level of platelet aggregation is significantly lower in patients treated with 150 mg per day than in those treated with 75 mg per day. Moreover, at least three other studies have shown that the antiplatelet effects of a 150 mg daily maintenance dose exceed those of a 75 mg daily maintenance dose.3–5 Zhang and Balavenkatesh suggest that the sample size calculation may not be valid since values for platelet aggregation were higher than expected. Interestingly, the relative difference in ADP (5 µM)-induced platelet aggregation 30 days after percutaneous coronary intervention (31 %) amounted quite accurately to what we had assumed1,6. Recalculating the sample size with the absolute values obtained actually increases the power of the study. Moreover, we believe that the sample size of our present study is far too small to allow conclusions on subgroups of patients (e.g. those who are females and those who have diabetes and peripheral artery disease). It should be mentioned, though, that just recently, Angiolillo et al.1 showed that an increase of the daily maintenance dose of clopidogrel from 75 to 150 mg per day also results in a significant reduction of the level of platelet aggregation in diabetics with a poor response to clopidogrel.
References
- von Beckerath N, Kastrati A, Wieczorek A, Pogatsa-Murray G, Sibbing D, Graf I, Schömig A. A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days. Eur Heart J (2007) 28:1814–1819.
- Harrison P, Frelinger AL III, Furman MI, Michelson AD. Measuring antiplatelet drug effects in the laboratory. Thromb Res (2007) 120:323–336.
- Angiolillo DJ, Shoemaker SB, Desai B, Yuan H, Charlton RK, Bernardo E, Zenni MM, Guzman LA, Bass TA, Costa MA. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) study. Circulation (2007) 115:708–716.
- Fontana P, Senouf D, Mach F. Biological effect of increased maintenance dose of clopidogrel in cardiovascular outpatients and influence of the cytochrome P450 2C19 2 allele on clopidogrel responsiveness. Thromb Res (2007) 1:1.
- Hochholzer W, Trenk D, Müller B, Valina CM, Stratz C, Bestehorn HP, Büttner HJ, Neumann F. Efficacy of adjusted clopidogrel dosing in patients with insufficient platelet inhibition after elective coronary stenting: the ExcelsiorACT study. (Abstract). Eur Heart J (2006) 27(Suppl):750.
- Kastrati A, von Beckerath N, Joost A, Pogatsa-Murray G, Gorchakova O, Schömig A. Loading with 600 mg clopidogrel in patients with coronary artery disease with and without chronic clopidogrel therapy. Circulation (2004) 110:1916–1919.
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