Pharmacodynamic Evaluation of Switching From Prasugrel to Ticagrelor

Dual antiplatelet therapy consisting of aspirin and a P2Y12 receptor antagonist is the
cornerstone of treatment for secondary prevention of thrombotic events in patients with
coronary artery disease. Recently, two new oral P2Y12 antagonists have been approved for
clinical use: prasugrel, a third generation thienopyridine, and ticagrelor, a first in class
cyclopentyltriazolopyrimidine (CPTP). These agents have been shown to be associated with
more potent platelet inhibitory effects compared with clopidogrel. In addition, both agents
have shown to be superior to clopidogrel in preventing recurrent ischemic events in the
setting of acute coronary syndromes (ACS). Therefore, current guidelines recommend prasugrel
or ticagrelor (as first line therapy according to European Society of Cardiology) in ACS
patients undergoing percutaneous coronary intervention (PCI). Despite the broader indication
for ticagrelor (also medically managed ACS) and its mortality benefit, prasugrel has a
higher uptake than ticagrelor in the US market, likely due to its earlier approval. Further,
implementation of prasugrel into institutional protocols, particularly for ST elevation
myocardial infarction (STEMI) patients undergoing primary PCI, may also be a reason for the
slow uptake of ticagrelor. However, many clinicians would indeed consider ticagrelor as the
long-term treatment of choice for a variety of reasons. Therefore, understanding how to
switch patients from prasugrel to ticagrelor is an unmet need of clinical interest. However,
currently, there are no data on the pharmacodynamic (PD) effects of switching from prasugrel
to ticagrelor. The proposed PD investigation will have a prospective, randomized, parallel
design aimed to show that switching patients from prasugrel to ticagrelor provides similar
levels of platelet inhibition. This study will provide insights on the PD effects of
switching and will help clinicians to choose the most appropriate schema to avoid
complications related to inadequate antiplatelet therapy in patients with coronary artery
disease if switching from prasugrel to ticagrelor is desired.

Inclusion Criteria:

- Patients with known coronary artery disease who presented with and ACS and underwent
PCI.

- Age between 18 and 74 years old.

- On therapy with low-dose aspirin (81 mg) and prasugrel 10 mg/daily for at least 14
days as per standard of care

Exclusion criteria:

- History of stroke, transient ischemic attack (TIA) or intracranial bleeding.

- Known allergies to ticagrelor.

- Weight < 60 Kg

- On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran,
rivaroxaban).

- Treatment with IIb/IIIa glycoprotein inhibitors in the last 7 days.

- Blood dyscrasia or bleeding diathesis.

- Platelet count <80x106/mL.

- Hemoglobin <10 g/dL.

- Active bleeding.

- Hemodynamic instability.

- Creatinine Clearance <30 mL/minute.

- Known severe hepatic dysfunction.

- Patients with sick sinus syndrome (SSS) or high degree atrio-ventricular block
without pacemaker protection.

- Current treatment with drugs interfering with cytochrom P450 3A4 metabolism (to avoid
interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole,
clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir,
and telithromycin.

- Pregnant females.