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

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.

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.