Prasugrel With Lower Dose - Loading Dose

Study Overview
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Brief Summary
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Although prasugrel, recently available thienopyridine derivative, exhibits rapid and potent platelet inhibition, concerns of low on-treatment platelet reactivity have been suggested especially in East Asian ethnicities. The investigators compared the effect of lower loading dose of prasugrel with conventional loading dose of clopidogrel and prasugrel.

Detailed Description
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Although clopidogrel together aspirin has been a backbone of anti-platelet therapy in coronary artery disease patients, clopidogrel has several limitations. It has delayed onset of peak concentration and pharmacodynamic inter-patient response variability resulting in high on-treatment platelet reactivity (HPR). Those demerits are known to be associated with adverse cardiovascular outcomes. Prasugrel has a more effective metabolism pathway than clopidogrel and exhibits more rapid and potent platelet inhibition. Recent guidelines recommend prasugrel as a first line antiplatelet agent or put precedence over clopidogrel for the patients with acute coronary syndrome. However, there have been concerns of different pharmacodynamic and pharmacokinetic response to prasugrel in East Asian ethnicities. In addition, lower loading dose of prasugrel exhibited more potent pharmacodynamic effect than clopidogrel 600 mg with comparable efficacy compared to conventional loading dose of prasugrel in healthy Korean subjects. The investigators compare the antiplatelet effect of lower loading dose of prasugrel 30 mg with conventional loading dose of clopidogrel 600 mg and prasugrel 60 mg in Korean coronary artery disease patients undergoing elective coronary angiography.

Official Title
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Effect of Lower Loading Dose of Prasugrel Compared With Conventional Loading Dose of Clopidogrel and Prasugrel in Korean Coronary Artery Disease Patients Undergoing Coronary Angiography

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Clopidogrel 600 mg
* Drug: Prasugrel 30 mg
* Drug: Prasugrel 60 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between 18 and 80 years Stable or unstable angina Planned to undergo elective coronary angiography Exclusion Criteria: Previous history of transient ischemic attack or stroke Intracranial neoplasm Uncontrolled malignant disease History of antiplatelet or anticoagulation treatment within 1 month Contraindication to the study drug Bleeding diathesis Hemoglobin < 10 g/dl Platelet count < 100,000/mm3 Significant renal insufficiency (glomerular filtration rate <60 mL/min/1.73 m2) Significant hepatic impairment (Serum liver enzyme or bilirubin > 3 times normal limit) Body weight < 50 kg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clopidogrel 600 mg<br>Patients administer conventional loading dose of clopidogrel 600 mg as active comparators. | Drug: Clopidogrel 600 mg<br>* Patients administer 600 mg of clopidogrel as conventional loading dose of clopidogrel<br>* Other names: Plavix 600 mg;|
| Experimental: Prasugrel 30 mg<br>Patients administer lower loading dose of prasugrel 30 mg. | Drug: Prasugrel 30 mg<br>* Patients administer 30 mg of prasugrel as lower loading dose of prasugrel.<br>* Other names: Effient 30 mg;|
| Active Comparator: Prasugrel 60 mg<br>Patients administer conventional loading dose of prasugrel 60 mg as active comparators. | Drug: Prasugrel 60 mg<br>* Patients take 60 mg of prasugrel as conventional loading dose of prasugrel.<br>* Other names: Effient 60 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet reactivity | Platelet reactivity was measured using traditional light transmission aggregometry (LTA), VerifyNow (Accumetrics, San Diego, CA, USA), and multiple electrode aggregometry (MEA, Dynabyte Medical, Munich, Germany). The platelet reactivity was measured at 6 hours after study drug administration (after 2 hours for the prasugrel groups). | at 6 hours after administration of study drug. (2 hours for prasugrel groups) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent inhibition | Percent inhibition is calculated using the following fomula: % inhibition = [(baseline reactivity unit - peak reactivity unit) / baseline reactivity unit] × 100. Percent inhibition is measured at the time of peak platelet inhibition. The platelet reactivity was measured at 6 hours after study drug administration (after 2 hours for the prasugrel groups). | at 6 hours after administration of study drug. (2 hours for prasugrel groups) | 
| HPR | The high platelet reactivity (HPR) was defined as the results of LTA ≥ 48% or ≥ 55%, PRU ≥ 242 or ≥ 275, and result of MEA assay ≥ 37 U or 54 U at the time of peak platelet inhibition The platelet reactivity was measured at 6 hours after study drug administration (after 2 hours for the prasugrel groups). | at 6 hours after administration of study drug. (2 hours for prasugrel groups) | 
| LPR | The low platelet reactivity (LPR) was defined as LTA < 12, PRU < 85, MEA < 19 at the time of peak platelet inhibition. The platelet reactivity was measured at 6 hours after study drug administration (after 2 hours for the prasugrel groups). | at 6 hours after administration of study drug. (2 hours for prasugrel groups) | 
| Bleeding event | Any event related to bleeding including access site bleeding and peri-procedural bleeding based on BARC and ACUITY criteria. | 30 days after study drug administration | 
| Adverse reaction | Any adverse reaction related to study drug. | 30 days after study drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronary artery disease, prasugrel, platelet function tests