Clinical InvestigationCoronary Artery DiseaseA comparison of prasugrel and clopidogrel loading doses on platelet function: magnitude of platelet inhibition is related to active metabolite formation
Section snippets
Study design and subjects
This was a phase 1 randomized, 2-way crossover, open-label study in healthy subjects conducted at a single center from September to November 2003. The study was approved by the local investigational review board, and subjects provided written informed consent before enrolling in the study. Sixty-eight subjects were randomly allocated to receive either prasugrel 60 mg (15 mg as the HCl salt, 4 tablets, Eli Lilly and Co, Indianapolis, IN) or clopidogrel 300 mg (75 mg, 4 tablets, Plavix,
Results
Sixty-eight healthy subjects were enrolled in this study. The majority of the subjects were men (n = 48, 71%) and the mean ± SD age was 42 ± 17 years. Their average weight was 76.3 ± 11.6 kg, and their average body mass index was 24.7 ± 3.7 kg/m2.
Two subjects randomly allocated to receive prasugrel during the first dosing period were withdrawn from the study before the second dosing period; 1 for taking medications not permitted by the study protocol and the other for personal reasons. Two
Discussion
Studies in animals have demonstrated that prasugrel has a more rapid onset and is a more potent inhibitor of platelet P2Y12 function than clopidogrel or ticlopidine.8, 23 The results from the present study extend these findings to healthy human subjects. Prasugrel 60 mg LD was associated with more rapid, more consistent, and significantly greater inhibition of platelet aggregation than was clopidogrel 300-mg LD. The faster onset of platelet inhibition after prasugrel was evident in a number of
References (38)
- et al.
Acute and nine-month clinical outcomes after “suboptimal” coronary stenting: results from the STent Anti-thrombotic Regimen Study (STARS) registry
J Am Coll Cardiol
(1999) - et al.
Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: The PCI-CURE study
Lancet
(2001) - et al.
Frequency of nonresponse antiplatelet activity of clopidogrel during pretreatment for cardiac catheterization
Am J Cardiol
(2004) - et al.
Variability in platelet responsiveness to clopidogrel among 544 individuals
J Am Coll Cardiol
(2005) - et al.
High post-treatment platelet reactivity identified low-responders to dual antiplatelet therapy at increased risk of recurrent cardiovascular events after stenting for acute coronary syndrome
J Thromb Haemost
(2006) - et al.
Resistance to clopidogrel: a review of the evidence
J Am Coll Cardiol
(2005) - et al.
Matching the evaluation of the clinical efficacy of clopidogrel to platelet function tests relevant to the biological properties of the drug
J Am Coll Cardiol
(2005) - et al.
ACC/AHA guidelines for the management of patients with unstable angina and non–ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the management of patients with unstable angina)
J Am Coll Cardiol
(2000) Antiplatelet therapy in non–ST-segment elevation acute coronary syndromes
JAMA
(2004)- et al.
Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (FANTASTIC) study
Circulation
(1998)
A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel
N Engl J Med
Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary stent implantation in high-risk patients: the multicenter aspirin and ticlopidine trial after intracoronary stenting (MATTIS)
Circulation
Pharmacology of CS-747 (Prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y(12) receptor antagonist activity
Semin Thromb Hemost
Clopidogrel and ticlopidine: P2Y(12) adenosine diphosphate-receptor antagonists for the prevention of atherothrombosis
Semin Thromb Hemost
Clopidogrel
Drugs
Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS)
Circulation
The inter-individual variability of the response to clopidogrel
Arch Mal Coeur Vaiss
Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity
Circulation
Individual variations of platelet inhibition after loading doses of clopidogrel
J Intern Med
Cited by (539)
Aptamer-based regulation of DNA polymerase activity for the detection of protein-small molecule interactions
2023, Biosensors and Bioelectronics: XAntiplatelet Agents in Acute ST Elevation Myocardial Infarction
2022, American Journal of MedicineP2Y12 inhibition in acute coronary syndromes treated with percutaneous intervention – Understanding the debate on Prasugrel or Ticagrelor
2022, Pharmacology and TherapeuticsIschemic and Bleeding Outcomes of Potent P2Y12 Inhibitor Antiplatelet Agents Versus Clopidogrel in Elderly Patients With Acute Coronary Syndrome: A Meta-Analysis of Randomized Trials
2022, Cardiovascular Revascularization MedicineNOD2-mediated P2Y<inf>12</inf> upregulation increases platelet activation and thrombosis in sepsis
2021, Biochemical Pharmacology
This study was funded by Eli Lilly and Company and Sankyo Co, Ltd., Tokyo, Japan.