Prasugrel compared with high-dose clopidogrel in acute coronary syndrome. The randomised, double-blind ACAPULCO study.
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 microM 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.
Montalescot
Gilles
G
Institut de Cardiologie (AP-HP), INSERM U856 and Universite Paris 6, Hopital Pitié-Salpetrière, Paris, France. gilles.montalescot@psl.aphp.fr
Sideris
Georgios
G
Cohen
Remy
R
Meuleman
Catherine
C
Bal dit Sollier
Claire
C
Barthélémy
Olivier
O
Henry
Patrick
P
Lim
Pascal
P
Beygui
Farzin
F
Collet
Jean-Philippe
JP
Marshall
Debra
D
Luo
Junxiang
J
Petitjean
Helene
H
Drouet
Ludovic
L
D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy*; D000244:Adenosine Diphosphate; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077144:Clopidogrel; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010297:Paris; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine