Switching From Ticagrelor to Clopidogrel in Patients With Coronary Artery Disease

The recommended antiplatelet treatment regimen for patients affected by acute coronary
syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI) consists in the
combination of aspirin and a P2Y12 receptor inhibitor. Currently, three P2Y12 receptor
inhibitors are available for clinical use (clopidogrel, prasugrel, and ticagrelor). Among
these, clopidogrel remains the most widely used. However, recent studies have shown that
there is a broad variability in platelet-inhibitory response induced by clopidogrel, which in
turn is associated with worse outcomes. More potent P2Y12 receptor inhibitors (prasugrel and
ticagrelor) have been developed which are associated with less response variability than
clopidogrel and better clinical outcomes. Ticagrelor use has increased significantly because
of its more expanded Food and Drug Administration (FDA) indications compared with prasugrel.
However, despite the evidence for sustained efficacy and safety, many physicians limit
treatment duration with ticagrelor to the early phases following an ACS (early weeks or
months, rather than one-year) mostly due to cost issues and concerns about increased
bleeding. Therefore, it is very common in clinical practice to switch patients while on
maintenance dosing (MD) with ticagrelor to treatment with clopidogrel. However, the
pharmacodynamic (PD) effects of switching from ticagrelor to clopidogrel remain unknown. In
addition, it is unknown whether switching from ticagrelor to clopidogrel should occur with or
without a loading dose (LD). Therefore, the aim of this investigation is to evaluate the PD
effects of switching from ticagrelor to clopidogrel with and without a LD. The present study
has a prospective, randomized, open-label design, in which patients will be treated with 4
different strategies to assess PD profiling after switching. This study will provide
important insights on PD effects of switching from ticagrelor to clopidogrel.

Inclusion Criteria

1. Patients with angiographically documented CAD

2. On therapy with aspirin(<100mg/day) and clopidogrel (75mg/day) for at least 30 days
per standard of care

3. Age between 18 and 80 years old

Exclusion Criteria

1. History of intracranial bleeding

2. Severe hepatic impairment (ALT >2.5 times the upper limit of normal)

3. Active bleeding or propensity to bleed or blood dycrasia

4. Platelet count <80x106/mL

5. Hemoglobin <10g/dL

6. Hemodynamic instability

7. Estimated glomerular filtration rate (eGFR) <30 mL/min

8. On treatment with oral anticoagulants

9. Patients with sick sinus syndrome (SSS) or II or III degree AV block without pacemaker
protection

10. Drugs interfering CYP3A4 metabolism (to avoid interaction with ticagrelor):
ketoconazole, itraconazole, voriconazole, clarithromicin, nefazodone, ritonavir,
saquinavir, nelfinavir, indinavir, atazanavir and telithromizycin

11. Pregnant females [women of childbearing age must use reliable birth control (i.e. oral
contraceptives) while participating in the study].