TY - JOUR
T1 - A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease
T2 - Results of the Optimizing anti-Platelet Therapy in diabetes MellitUS (OPTIMUS)-3 Trial
AU - Angiolillo, Dominick J.
AU - Badimon, Juan Jose
AU - Saucedo, Jorge F.
AU - Frelinger, Andrew L.
AU - Michelson, Alan D.
AU - Jakubowski, Joseph A.
AU - Zhu, Baojin
AU - Ojeh, Clement K.
AU - Baker, Brian A.
AU - Effron, Mark B.
N1 - Funding Information:
This work was supported by Daiichi Sankyo, Inc., and Eli Lilly and Company. Funding to pay the Open Access publication charges for this article was provided by Eli Lilly and Company.
PY - 2011/4
Y1 - 2011/4
N2 - Aims Patients with diabetes mellitus (DM) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM. Prasugrel, a more potent antiplatelet agent, is associated with greater reductions in ischaemic events compared with clopidogrel, particularly in patients with DM. The aim of this study was to perform serial pharmacodynamic assessments of prasugrel with high-dose clopidogrel in patients with DM. Methods and resultsOptimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospective, randomized, double-blind, crossover study in patients with type 2 DM and coronary artery disease (CAD). Patients (n 35) were randomly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period. Platelet function was assessed by VerifyNow ® P2Y12 assay, light transmission aggregometry, and vasodilator-stimulated phosphoprotein phosphorylation at 0, 1, 4, and 24 h and 7 days. Greater platelet inhibition by VerifyNow ® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD (least squares mean, 89.3 vs. 27.7, P< 0.0001; primary endpoint). The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days (P < 0.0001). Similar results were obtained using all other platelet function measures. Prasugrel resulted in fewer poor responders at all time points irrespective of definition used. ConclusionIn patients with type 2 DM and CAD, standard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel.Clinical trial identifier: www.clinicaltrials.govNCT00642174.
AB - Aims Patients with diabetes mellitus (DM) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM. Prasugrel, a more potent antiplatelet agent, is associated with greater reductions in ischaemic events compared with clopidogrel, particularly in patients with DM. The aim of this study was to perform serial pharmacodynamic assessments of prasugrel with high-dose clopidogrel in patients with DM. Methods and resultsOptimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospective, randomized, double-blind, crossover study in patients with type 2 DM and coronary artery disease (CAD). Patients (n 35) were randomly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period. Platelet function was assessed by VerifyNow ® P2Y12 assay, light transmission aggregometry, and vasodilator-stimulated phosphoprotein phosphorylation at 0, 1, 4, and 24 h and 7 days. Greater platelet inhibition by VerifyNow ® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD (least squares mean, 89.3 vs. 27.7, P< 0.0001; primary endpoint). The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days (P < 0.0001). Similar results were obtained using all other platelet function measures. Prasugrel resulted in fewer poor responders at all time points irrespective of definition used. ConclusionIn patients with type 2 DM and CAD, standard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel.Clinical trial identifier: www.clinicaltrials.govNCT00642174.
KW - Coronary disease
KW - Diabetes mellitus
KW - Platelets
UR - http://www.scopus.com/inward/record.url?scp=79952149001&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/ehq494
DO - 10.1093/eurheartj/ehq494
M3 - Article
C2 - 21252171
AN - SCOPUS:79952149001
SN - 0195-668X
VL - 32
SP - 838
EP - 846
JO - European Heart Journal
JF - European Heart Journal
IS - 7
ER -