European Heart Journal Advance Access originally published online on April 18, 2006
European Heart Journal 2006 27(10):1166-1173; doi:10.1093/eurheartj/ehi877
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Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease
1 Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, University Hospital, 751 85 Uppsala, Sweden
2 Lilly Research Centre Ltd., Windlesham, Surrey, UK
3 Eli Lilly and Company, Indianapolis, IN, USA
4 Clinical Pharmacology and Biostatistics Department, Sankyo Co. Ltd., Tokyo, Japan
5 Department of Medical Sciences, Clinical Chemistry, University Hospital, Uppsala, Sweden
Received 3 September 2005; revised 6 March 2006; accepted 23 March 2006; online publish-ahead-of-print 18 April 2006.
* Corresponding author. Tel: +46 18 611 00 00; fax: +46 18 50 66 38. E-mail address: lars.wallentin{at}ucr.uu.se
Aims This study was designed to compare the degree of inhibition of platelet aggregation (IPA) of prasugrel with that of clopidogrel in stable aspirin-treated patients with coronary artery disease (CAD).
Methods and results Subjects (n=101) were randomly assigned to the following loading dose (LD) (day 1)/maintenance dose (MD) (days 2–28) combinations: prasugrel, 40 mg/5 mg; 40 mg/7.5 mg; 60 mg/10 mg; 60 mg/15 mg; or clopidogrel, 300 mg/75 mg. Turbidometric platelet aggregation was measured at multiple timepoints during the study. At 4 h after dosing, with 20 µM ADP, both prasugrel LDs achieved significantly higher mean IPA levels (60.6% and 68.4 vs. 30.0%, respectively; all P<0.0001) and lower percentage (3 vs. 52%, P<0.0001) of pharmacodynamic non-responders (defined as IPA <20%) than clopidogrel. Prasugrel 10 and 15 mg MDs achieved consistently higher mean IPA than clopidogrel 75 mg at day 28 (all P<0.0001). At pre-MD on day 28, there were no non-responders in the 10 and 15 mg prasugrel group, compared with 45% in the clopidogrel group (P=0.0007).
Conclusion In this population, prasugrel (40–60 mg LD and 10–15 mg MD) achieves greater IPA and a lower proportion of pharmacodynamic non-responders compared with the approved clopidogrel dosing.
Key Words: Prasugrel • CS-747 • Thienopyridine • Clopidogrel • Platelets • Trials
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