Prasugrel compared with high-dose clopidogrel in acute coronary syndrome

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Issue: 2010: 103/1 (Jan) pp. 1–249
Pages: 213-223

Prasugrel compared with high-dose clopidogrel in acute coronary syndrome

The randomised, double-blind ACAPULCO* study

G. Montalescot (1), G. Sideris (2), R. Cohen (3), C. Meuleman (4), C. Bal dit Sollier (2), O. Barthélémy (1), P. Henry (2), P. Lim (3), F. Beygui (1), J.-P. Collet (1), D. Marshall (5), J. Luo (5), H. Petitjean (6), L. Drouet (2)

(1) Institut de Cardiologie (AP-HP), INSERM U856 and Université Paris 6, Hôpital Pitié-Salpêtrière, Paris, France; (2) Hôpital Lariboisière and Université Paris 7, Paris, France; (3) Hôpital H Mondor and Université Paris 12, Paris, France; (4) Hôpital Saint-Antoine and Université Paris 6, Paris, France; (5) Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA; (6) Daiichi Sankyo, Inc., Parsippany, New Jersey, USA


prasugrel, high-dose clopidogrel, thienopyridine switching


Compared with the approved dose regimen of clopidogrel (300-mg loading dose [LD], 75-mg maintenance dose [MD]), prasugrel has been demonstrated to reduce ischaemic events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). In ACS, antiplatelet effects of a prasugrel MD regimen have not been previously compared with either a higher clopidogrel MD or after switching from a higher clopidogrel LD. The objective of this study was to evaluate the antiplatelet effect of a prasugrel 10-mg MD versus a clopidogrel 150-mg MD in patients with ACS who had received a clopidogrel 900-mg LD. Patients with non-ST elevation ACS, treated with aspirin and a clopidogrel 900-mg LD, were randomised within 24 hours post-LD to receive a prasugrel 10-mg or clopidogrel 150-mg MD. After 14 days of the initial MD, subjects switched to the alternative treatment for 14 days. The primary endpoint compared maximum platelet aggregation (MPA, 20 µM adenosine diphosphate [ADP]) between prasugrel and clopidogrel MDs for both periods. Responder analyses between treatments were performed using several platelet-function methods. Of 56 randomised subjects, 37 underwent PCI. MPA was 26.2% for prasugrel 10 mg and 39.1% for clopidogrel 150 mg (p<0.001). The prasugrel MD regimen reduced MPA from the post-900-mg LD level (41.2% to 29.1%, p=0.003). Poor response ranged from 0% to 6% for prasugrel 10 mg and 4% to 34% for clopidogrel 150 mg. Thus, in ACS patients a prasugrel 10-mg MD regimen resulted in significantly greater platelet inhibition than clopidogrel at twice its approved MD or a 900-mg LD.

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