TY - JOUR
T1 - Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention
T2 - The prasugrel in comparison to clopidogrel for inhibition of platelet activation and aggregation-thrombolysis in myocardial infarction 44 trial
AU - Wiviott, Stephen D.
AU - Trenk, Dietmar
AU - Frelinger, Andrew L.
AU - O'Donoghue, Michelle
AU - Neumann, Franz Josef
AU - Michelson, Alan D.
AU - Angiolillo, Dominick J.
AU - Hod, Hanoch
AU - Montalescot, Gilles
AU - Miller, Debra L.
AU - Jakubowski, Joseph A.
AU - Cairns, Richard
AU - Murphy, Sabina A.
AU - McCabe, Carolyn H.
AU - Antman, Elliott M.
AU - Braunwald, Eugene
PY - 2007/12
Y1 - 2007/12
N2 - BACKGROUND - The increasing use of higher-than-approved doses of clopidogrel in clinical practice is based in part on the desire for greater levels of inhibition of platelet aggregation (IPA). Prasugrel is a new thienopyridine that is more potent than standard-dose clopidogrel in healthy subjects and patients with stable coronary artery disease. The relative antiplatelet effects of prasugrel versus high-dose clopidogrel in percutaneous coronary intervention patients are unknown. METHODS AND RESULTS - Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 (PRINCIPLE-TIMI 44) was a randomized, double-blind, 2-phase crossover study of prasugrel compared with high-dose clopidogrel in patients undergoing cardiac catheterization for planned percutaneous coronary intervention. The primary end point of the loading-dose phase (prasugrel 60 mg versus clopidogrel 600 mg) was IPA with 20 μmol/L ADP at 6 hours. Patients with percutaneous coronary intervention entered the maintenance-dose phase, a 28-day crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a primary end point of IPA after 14 days of either drug. In this study, 201 subjects were randomized. IPA at 6 hours was significantly higher in subjects receiving prasugrel (mean±SD, 74.8±13.0%) compared with clopidogrel (31.8±21.1%; P<0.0001). During the maintenance-dose phase, IPA with 20 μmol/L ADP was higher in subjects receiving prasugrel (61.3±17.8%) compared with clopidogrel (46.1±21.3%; P<0.0001). Results were consistent across all key secondary end points; significant differences emerged by 30 minutes and persisted across all time points. CONCLUSIONS - Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention, loading with 60 mg prasugrel resulted in greater platelet inhibition than a 600-mg clopidogrel loading dose. Maintenance therapy with prasugrel 10 mg/d resulted in a greater antiplatelet effect than 150 mg/d clopidogrel.
AB - BACKGROUND - The increasing use of higher-than-approved doses of clopidogrel in clinical practice is based in part on the desire for greater levels of inhibition of platelet aggregation (IPA). Prasugrel is a new thienopyridine that is more potent than standard-dose clopidogrel in healthy subjects and patients with stable coronary artery disease. The relative antiplatelet effects of prasugrel versus high-dose clopidogrel in percutaneous coronary intervention patients are unknown. METHODS AND RESULTS - Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 (PRINCIPLE-TIMI 44) was a randomized, double-blind, 2-phase crossover study of prasugrel compared with high-dose clopidogrel in patients undergoing cardiac catheterization for planned percutaneous coronary intervention. The primary end point of the loading-dose phase (prasugrel 60 mg versus clopidogrel 600 mg) was IPA with 20 μmol/L ADP at 6 hours. Patients with percutaneous coronary intervention entered the maintenance-dose phase, a 28-day crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a primary end point of IPA after 14 days of either drug. In this study, 201 subjects were randomized. IPA at 6 hours was significantly higher in subjects receiving prasugrel (mean±SD, 74.8±13.0%) compared with clopidogrel (31.8±21.1%; P<0.0001). During the maintenance-dose phase, IPA with 20 μmol/L ADP was higher in subjects receiving prasugrel (61.3±17.8%) compared with clopidogrel (46.1±21.3%; P<0.0001). Results were consistent across all key secondary end points; significant differences emerged by 30 minutes and persisted across all time points. CONCLUSIONS - Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention, loading with 60 mg prasugrel resulted in greater platelet inhibition than a 600-mg clopidogrel loading dose. Maintenance therapy with prasugrel 10 mg/d resulted in a greater antiplatelet effect than 150 mg/d clopidogrel.
KW - Anticoagulants
KW - Antiplatelet agents
KW - Coronary disease
KW - Platelets
KW - Thrombosis
UR - http://www.scopus.com/inward/record.url?scp=37349111065&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.107.740324
DO - 10.1161/CIRCULATIONAHA.107.740324
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AN - SCOPUS:37349111065
VL - 116
SP - 2923
EP - 2932
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 25
ER -