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

• Published in: European heart journal Vol. 27; no. 10; pp. 1166 - 1173
• Main Authors: JERNBERG, Tomas, PAYNE, Christopher D, WINTERS, Kenneth J, DARSTEIN, Christelle, BRANDT, John T, JAKUBOWSKI, Joseph A, NAGANUMA, Hideo, SIEGBAHN, Agneta, WALLENTIN, Lars
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2006; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Aspirin - administration & dosage; Aspirin - adverse effects; Biological and medical sciences; Cardiology. Vascular system; Coronary Artery Disease - drug therapy; Coronary heart disease; Drug Therapy, Combination; Female; Heart; Humans; Male; Medical sciences; MEDICIN; MEDICINE; Middle Aged; Piperazines - administration & dosage; Piperazines - adverse effects; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; Prasugrel Hydrochloride; Thiophenes - administration & dosage; Thiophenes - adverse effects; Ticlopidine - administration & dosage; Ticlopidine - adverse effects; Ticlopidine - analogs & derivatives; Human; Rate; CS-747; Cardiovascular disease; Thienopyridine; Acetylsalicylic acid; Coronary heart disease; Phlebology; Aggregation; Prasugrel; Platelet; Treatment; Trials; Clopidogrel; Circulatory system; Inhibition; Cardiology; Platelets; Comparative study; Responder
• ISSN: 0195-668X; 1522-9645; 1522-9645
• DOI: 10.1093/eurheartj/ehi877

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). 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 microM 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). 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.