Coronary Artery Disease
Conditions
Keywords
Coronary artery disease, Dual antiplatelet therapy, prasugrel, ticagrelor
Brief summary
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
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.
Interventions
DRUGTicagrelor
Ticagrelor 180mg loading dose and 90mg bid maintenance dose
DRUGPrasugrel
Prasugrel 60mg loading dose and 10mg maintenance dose
Sponsors
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) | 1 week | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP) | 2 hours | 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. |
Countries
United States
Participant flow
Recruitment details
Between December 2011 to June 2014 patients were screened at the outpatient cardiology clinics, UF Health, University of Florida, Jacksonville.
Participants by arm
| Arm | Count |
|---|---|
| Prasugrel Prasugrel 60mg loading dose and 10 mg maintenance dose | 55 |
| Ticagrelor Ticagrelor 180mg loading dose and 90mg bid maintenance dose | 55 |
| Total | 110 |
Baseline characteristics
| Characteristic | Ticagrelor | Total | Prasugrel |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 28 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 82 Participants | 41 Participants |
| Region of Enrollment United States | 55 participants | 110 participants | 55 participants |
| Sex: Female, Male Female | 26 Participants | 45 Participants | 19 Participants |
| Sex: Female, Male Male | 29 Participants | 65 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 55 | 5 / 55 |
| serious Total, serious adverse events | 0 / 55 | 0 / 55 |
Outcome results
Primary
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.
Time frame: 1 week
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) | 32.1 PRI% | Standard Error 2.5 |
| Ticagrelor | Platelet Reactivity by Vasodilator-stimulated Phosphoprotein (VASP) | 32.6 PRI% | Standard Error 2.7 |
Secondary
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.
Time frame: 2 hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP) | 13.4 PRI% | Standard Error 2.7 |
| Ticagrelor | Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP) | 15.6 PRI% | Standard Error 3 |
Secondary
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.
Time frame: 24 hours
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Prasugrel | Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP) | 14.2 PRI% | Standard Error 2.2 |
| Ticagrelor | Platelet Reactivity Measured by Vasodilator-stimulated Phosphoprotein (VASP) | 26.4 PRI% | Standard Error 2.2 |