Pharmacodynamic Effects of Prasugrel Compared With Ticagrelor in Patients With Coronary Artery Disease

Study Overview
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Brief Summary
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Recently, two P2Y12 receptor inhibitors have been approved for clinical use: prasugrel and ticagrelor. Both prasugrel and ticagrelor have shown to be associated with more potent antiplatelet effects compared with clopidogrel and are associated with an improved net clinical benefit. However, to date there are limited head-to-head comparisons of these two new agents.

Detailed Description
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Dual antiplatelet therapy consisting of aspirin and clopidogrel is the cornerstone of treatment for prevention of thrombotic events in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). However, there are a considerable number of patients who continue to have recurrent ischemic events despite this treatment regimen. These observations underscore the need for more potent antiplatelet therapies. Recently, two P2Y12 receptor inhibitors have been approved for clinical use: prasugrel and ticagrelor. Both prasugrel and ticagrelor have shown to be associated with more potent antiplatelet effects compared with clopidogrel. These more favorable pharmacodynamic effects translate into reduced ischemic event rates, at the expense of an increased risk of bleeding in patients with acute coronary syndromes. Overall, these drugs are associated with an improved net clinical benefit. These findings from large-scale clinical investigations have led to approval of prasugrel and ticagrelor. However, to date there are limited head-to-head comparisons of these two new agents.

Official Title
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A head-to Head Comparison of the Pharmacodynamic Effects of Prasugrel Compared With Ticagrelor in Patients With Coronary Artery Disease

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Prasugrel
* Drug: Ticagrelor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with known coronary artery disease On maintenance treatment with aspirin (81 mg per day) and clopidogrel (75 mg per day) for at least 1-month as per standard of care. Age between 18 and 74 years old. Exclusion Criteria: History of stroke, transient ischemic attack or intracranial bleeding. Known allergies to aspirin, prasugrel, ticagrelor, or clopidogrel. Weight <60kg On treatment with oral anticoagulation (coumarin derivate, dabigatran). Hemoglobin<10 gm/dL Platelet count <80x106/mL Active bleeding or hemodynamic instability. Creatinine Clearance <30 mL/minute. Baseline ALT >2.5 times the upper limit of normal. Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection. Drugs interfering with 2C19 metabolism (to avoid interaction with clopidogrel): , fluconazole (Diflucan), ketoconazole (Nizoral), voriconazole (VFEND), etravirine (Intelence), felbamate (Felbatol), fluoxetine (Prozac, Serafem, Symbyax), fluvoxamine (Luvox), and ticlopidine (Ticlid). Drugs interfering CYP3A4 metabolism (to avoid interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromizycin. Pregnant females*. *Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Prasugrel<br>Prasugrel 60mg loading dose and 10 mg maintenance dose | Drug: Prasugrel<br>* Prasugrel 60mg loading dose and 10mg maintenance dose<br>* Other names: Effient;|
| Active Comparator: Ticagrelor<br>Ticagrelor 180mg loading dose and 90mg bid maintenance dose | Drug: Ticagrelor<br>* Ticagrelor 180mg loading dose and 90mg bid maintenance dose<br>* Other names: Brillinta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) | The primary end-point of the study was the comparison in the platelet reactivity index (PRI%) determined by vasodilator-stimulated phosphoprotein (VASP) at 1 week between prasugrel and ticagrelor. | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP) | A secondary outcome was the comparison between groups of platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein (VASP) at 2 hours after loading dose. | 2 hours | 
| Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP) | A secondary outcome was the comparison between groups of platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein (VASP) at 24 hours after loading dose. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary artery disease, Dual antiplatelet therapy, prasugrel, ticagrelor