Pharmacokinetics and Pharmacodynamics of Ticagrelor in Patients With Stable Angina, NSTEMI and STEMI Undergoing PCI

Inclusion Criteria:

- Stable Angina: Stable coronary artery disease patients with documented ischemia
undergoing elective PCI will be enrolled.Inclusion criteria for enrollment in the ACS
group with or without ST-segment elevation, requires onset of symptoms during the
previous 48 hours.

NSTEMI

For patients who had an ACS without ST-segment elevation (NTSEMI), two of the following
criteria had to be met:

- a positive test of a biomarker (troponin I) in accordance with the universal
definitions indicating myocardial necrosis

- ST-segment changes on electrocardiography, indicating ischemia that do not meet
criteria for STEMI.

STEMI

For patients who had an ACS with ST-segment elevation, the following two inclusion
criteria had to be met:

- either persistent ST-segment elevation of at least 0.1 mV in at least two contiguous
leads or a new left bundle-branch block; and

- the intention to perform primary PCI with 24 hours of symptom onset

Exclusion Criteria:

- Patients who are on P2Y12 receptor blockers, oral anticoagulants, or GPIIb/IIIa
receptor blocker therapies.

- Presence or history of any of the following: ischemic or hemorrhagic stroke;
transient ischemic attack (TIA); intracranial neoplasm; arteriovenous malformation,
or aneurysm; intracranial hemorrhage; head trauma (within 3 months of study entry)

- History of refractory ventricular arrhythmias or an increased risk of bradycardic
events (eg, subjects without a pacemaker who have sick sinus syndrome, 2nd or 3rd
degree atrioventricular (AV) block or bradycardic-related syncope)

- History or evidence of congestive heart failure (New York Heart Association Class III
or above ≤ 6 months before screening

- Severe hepatic impairment defined as ALT> 2.5 X ULN

- Uncontrolled hypertension, or systolic blood pressure > 180 mmHg or diastolic blood
pressure > 110 mmHg at screening

- Severely impaired renal function (glomerular filtration rate < 30 mL/minute) or on
dialysis

- Platelet count <100 X103, illicit drug or alcohol abuse, prothrombin time>1.5 times
control, haematocrit <30%, and creatinine >2.0 mg/dl.

- Contraindication or other reason that ticagrelor should not be administered (eg,
hypersensitivity, active bleeding, moderate or severe liver disease, history of
previous intracranial bleed, GI bleed within the past 6 months, major surgery within
30 days)

- Fibrinolytic therapy in the 24 hours prior to PCI, or planned fibrinolytic treatment
following PCI.

- Participation in another investigational drug or device study in the last 30
-Pregnancy or lactation

- Concomitant oral or intravenous therapy (see examples below) with strong CYP3A
inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A
inducers which cannot be stopped for the course of the study

- Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin,
clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir

- Substrates with narrow therapeutic index: cyclosporine, quinidine

- Strong inducers: rifampin/rifampicin, phenytoin, carbamazepine

- Any other condition which in the opinion of the investigator, may either put the
patient at risk or influence the result of the study (eg, cardiogenic shock or severe
haemodynamic instability, active cancer, risk for non-compliance, risk for being lost
to follow up)