Skip Navigation


European Heart Journal Advance Access originally published online on November 30, 2007
European Heart Journal 2008 29(1):21-30; doi:10.1093/eurheartj/ehm545
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
29/1/21    most recent
ehm545v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (51)
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Wallentin, L.
Right arrow Articles by Siegbahn, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wallentin, L.
Right arrow Articles by Siegbahn, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please e-mail: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org.

Prasugrel achieves greater and faster P2Y12receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin-treated patients with coronary artery disease

Lars Wallentin1,*, Christoph Varenhorst1, Stefan James1, David Erlinge2, Oscar Ö Braun2, Joseph A. Jakubowski3, Atsuhiro Sugidachi4, Kenneth J. Winters3 and Agneta Siegbahn5

1 Department of Medical Sciences and Cardiology, Uppsala Clinical Research Center, University Hospital, 751 85 Uppsala, Sweden
2 Department of Cardiology, Lund University, Sweden
3 Lilly Research Laboratories, IN, USA
4 Daiichi Sankyo Co., Ltd., Tokyo, Japan
5 Coagulation Laboratory, Department Medical Sciences, Uppsala, Sweden

Received 17 September 2007; revised 26 October 2007; accepted 29 October 2007; online publish-ahead-of-print 30 November 2007.

* Corresponding author. Tel: +46 18 611 95 07, Fax: +46 18 50 66 38, Email: lars.wallentin{at}ucr.uu.se

Aims: P2Y12 receptor antagonism and platelet inhibition by prasugrel vs. clopidogrel were investigated in patients with stable coronary artery disease.

Methods and results: One hundred and ten aspirin treated subjects were randomized to double-blind treatment with clopidogrel (n = 55) 600 mg loading dose (LD) and 75 mg maintenance dose (MD) or prasugrel (n = 55) 60 mg LD and 10 mg MD for 28 days. Concentrations of prasugrel and clopidogrel active metabolites were determined. Platelet aggregation to 20 µM adenosine diphosphate, measured by light transmission aggregometry, was reported as maximal platelet aggregation (MPA). P2Y12 function was assessed by the vasodilator-stimulated phosphoprotein assay and reported as platelet reactivity index (PRI). The same pharmacodynamic measurements were performed after ex vivo addition of clopidogrel’s active metabolite. At 2 h post-LD, mean MPA was 31 vs. 55%, and mean PRI 8.3 vs. 55.9% for prasugrel and clopidogrel, respectively (P < 0.001). During MD on day 14 and 28, mean MPA was 42 vs. 54% and mean PRI was 25 vs. 51%, respectively (P < 0.001). Peak level of the active metabolite and P2Y12 inhibition occurred earlier and was greater with prasugrel (P < 0.001). Mean area under the time-concentration curve (AUC; µM·h) of the respective active metabolite was higher with prasugrel vs. clopidogrel post-LD (1.11 vs. 0.24) and post-MD (0.16 vs. 0.062). Ex vivo addition of clopidogrel’s active metabolite further reduced PRI in all patients whose platelets were not already maximally inhibited.

Conclusion: In aspirin-treated subjects with coronary artery disease, prasugrel 60/10 mg provides faster onset and greater inhibition of P2Y12 receptor-mediated platelet aggregation than clopidogrel 600/75 mg, because of greater and more efficient generation of the active metabolite.

Key Words: Trials • Platelets • Coronary artery disease • Clopidogrel • Prasugrel


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
K. Hagihara, M. Kazui, A. Kurihara, M. Yoshiike, K. Honda, O. Okazaki, N. A. Farid, and T. Ikeda
A Possible Mechanism for the Differences in Efficiency and Variability of Active Metabolite Formation from Thienopyridine Antiplatelet Agents, Prasugrel and Clopidogrel
Drug Metab. Dispos., November 1, 2009; 37(11): 2145 - 2152.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
A. Schomig
Ticagrelor -- Is There Need for a New Player in the Antiplatelet-Therapy Field?
N. Engl. J. Med., September 10, 2009; 361(11): 1108 - 1111.
[Full Text] [PDF]

Home page
 NEJMHome page
L. Wallentin, R. C. Becker, A. Budaj, C. P. Cannon, H. Emanuelsson, C. Held, J. Horrow, S. Husted, S. James, H. Katus, et al.
Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes
N. Engl. J. Med., September 10, 2009; 361(11): 1045 - 1057.
[Abstract] [Full Text] [PDF]

Home page
 J CARDIOVASC PHARMACOL THERHome page
J.-P. Collet and G. Montalescot
Review: Platelet Function Testing and Implications for Clinical Practice
Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2009; 14(3): 157 - 169.
[Abstract] [PDF]

Home page
 JAMAHome page
A. R. Shuldiner, J. R. O'Connell, K. P. Bliden, A. Gandhi, K. Ryan, R. B. Horenstein, C. M. Damcott, R. Pakyz, U. S. Tantry, Q. Gibson, et al.
Association of Cytochrome P450 2C19 Genotype With the Antiplatelet Effect and Clinical Efficacy of Clopidogrel Therapy
JAMA, August 26, 2009; 302(8): 849 - 857.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
M. O'Donoghue, E. M. Antman, E. Braunwald, S. A. Murphy, P. G. Steg, A. Finkelstein, W. F. Penny, V. Fridrich, C. H. McCabe, M. S. Sabatine, et al.
The efficacy and safety of prasugrel with and without a glycoprotein IIb/IIIa inhibitor in patients with acute coronary syndromes undergoing percutaneous intervention: a TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) Analysis.
J. Am. Coll. Cardiol., August 18, 2009; 54(8): 678 - 685.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
A. Roguin
Magnetic resonance imaging in patients with implantable cardioverter-defibrillators and pacemakers.
J. Am. Coll. Cardiol., August 4, 2009; 54(6): 556 - 557.
[Full Text] [PDF]

Home page
 Eur Heart JHome page
L. Wallentin
P2Y12 inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use
Eur. Heart J., August 2, 2009; 30(16): 1964 - 1977.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
C. Verstuyft, T. Simon, and R. B. Kim
Personalized medicine and antiplatelet therapy: ready for prime time?
Eur. Heart J., August 2, 2009; 30(16): 1943 - 1963.
[Full Text] [PDF]

Home page
 J Clin PharmacolHome page
C. S. Ernest II, M. A. Heathman, and R. E. Wrishko
Prediction of Prasugrel Active Metabolite Concentrations From 2 Downstream Inactive Metabolite Concentrations Using Multilinear Regression Analysis
J. Clin. Pharmacol., August 1, 2009; 49(8): 973 - 983.
[Abstract] [Full Text] [PDF]

Home page
 J Clin PharmacolHome page
R. E. Wrishko, C. S. Ernest II, D. S. Small, Y. G. Li, G. J. Weerakkody, J. R. Riesmeyer, W. L. Macias, S. Rohatagi, D. E. Salazar, E. M. Antman, et al.
Population Pharmacokinetic Analyses to Evaluate the Influence of Intrinsic and Extrinsic Factors on Exposure of Prasugrel Active Metabolite in TRITON-TIMI 38
J. Clin. Pharmacol., August 1, 2009; 49(8): 984 - 998.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
C. Varenhorst, S. James, D. Erlinge, J. T. Brandt, O. O. Braun, M. Man, A. Siegbahn, J. Walker, L. Wallentin, K. J. Winters, et al.
Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease
Eur. Heart J., July 2, 2009; 30(14): 1744 - 1752.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
A. D. Michelson, A. L. Frelinger III, E. Braunwald, W. E. Downey, D. J. Angiolillo, N. P. Xenopoulos, J. A. Jakubowski, Y. Li, S. A. Murphy, J. Qin, et al.
Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial
Eur. Heart J., July 2, 2009; 30(14): 1753 - 1763.
[Abstract] [Full Text] [PDF]

Home page
 J Clin PharmacolHome page
N. F. Ford
Clopidogrel Resistance: Pharmacokinetic or Pharmacogenetic?
J. Clin. Pharmacol., May 1, 2009; 49(5): 506 - 512.
[Abstract] [Full Text] [PDF]

Home page
 Journal of Pharmacy PracticeHome page
A. Veverka and J. M. Hammer
Prasugrel: A New Thienopyridine Inhibitor
Journal of Pharmacy Practice, April 1, 2009; 22(2): 158 - 165.
[Abstract] [PDF]

Home page
 Eur Heart JHome page
W. Kuliczkowski, A. Witkowski, L. Polonski, C. Watala, K. Filipiak, A. Budaj, J. Golanski, D. Sitkiewicz, J. Pregowski, J. Gorski, et al.
Interindividual variability in the response to oral antiplatelet drugs: a position paper of the Working Group on antiplatelet drugs resistance appointed by the Section of Cardiovascular Interventions of the Polish Cardiac Society, endorsed by the Working Group on Thrombosis of the European Society of Cardiology
Eur. Heart J., February 2, 2009; 30(4): 426 - 435.
[Abstract] [Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
D. M. Scott, R. M Norwood, and D. Parra
P2Y12 Inhibitors in Cardiovascular Disease: Focus on Prasugrel
Ann. Pharmacother., January 1, 2009; 43(1): 64 - 76.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
J. A. Cairns and J. Eikelboom
The Pursuit of Clinically Relevant Measures of Platelet Function After Antiplatelet Drug Therapy
J. Am. Coll. Cardiol., December 9, 2008; 52(24): 1978 - 1980.
[Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
S. D. Kristensen, H. Baumgartner, B. Casadei, H. Drexler, E. Eeckhout, G. Filippatos, K. A.A. Fox, J. Perk, L. A. Pierard, D. Poldermans, et al.
Highlights of the 2008 Scientific Sessions of the European Society of Cardiology: Munich, Germany, August 30 to September 3, 2008
J. Am. Coll. Cardiol., December 9, 2008; 52(24): 2032 - 2042.
[Full Text] [PDF]

Home page
 J Am Coll Cardiol IntvHome page
D. J. Kereiakes and P. A. Gurbel
Peri-Procedural Platelet Function and Platelet Inhibition in Percutaneous Coronary Intervention
J. Am. Coll. Cardiol. Intv., April 1, 2008; 1(2): 111 - 121.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.