Ticagrelor Therapy for RefrACTORy Migraine Study

Migraine headaches are poorly understood, and can be severely debilitating. Many types of
drugs have been tried in migraine sufferers including anti-depressants, anti-seizure
medications, blood pressure medicines and others. The investigators have shown that in a
small number of patients, a certain type of blood thinner (Clopidogrel) can reduce or
eliminate migraine headaches in patients who also have a hole in the heart wall that allows
flow from the right side of the heart to the left. Ticagrelor is a blood thinning drug which
works in the same way as the clopidogrel, but is broken down by the body differently and
thus allows everyone to use it. The investigators wish to test this medication to see if it
works as well, or better than the clopidogrel.

Inclusion Criteria:

- At least one year history of Episodic or Chronic migraine headache symptoms

- At least 6 headache days per month

- Subject able to complete online daily headache log

Exclusion Criteria:

- Inability to understand the study or history of non-compliance with medical advice

- Currently taking a P2Y12 inhibitor

- Known hypersensitivity to Brilinta/ticagrelor

- History of stroke/transient ischemic attack (TIA) in the previous 6 months

- Active bleeding from any site

- Active peptic ulcer disease or upper gastrointestinal (GI) bleeding within six (6)
months

- Migraine onset after 50 years of age

- Renal impairment: Creatinine Clearance < 60 cc/min

- Severe hepatic impairment with total bilirubin > 3.0 mg/dL

- Thrombocytopenia with platelet count < 100,000 / ul

- History of intracranial hemorrhage

- Contraindications to blood thinner therapy or history of major bleeding episode while
taking blood thinner therapy

- Need for chronic oral anti-coagulation therapy (i.e. Atrial Fibrillation)

- Need for chronic anti-platelet therapy (i.e. drug-eluting (DE) Stent), including
daily aspirin use

- Need for daily nonsteroidal anti-inflammatory drug (NSAID) use

- Need for daily carbamazepine therapy or other strong CYP3A inhibitors or potent CYP3A
inducers

- Need for simvastatin or lovastatin greater than 40 mg daily

- Symptomatic bradycardia or syncope

- Pregnancy or currently breast-feeding, or plan to become pregnant during the study
period

- Planned surgery during the study time-frame

- Previously implanted patent foramen ovale (PFO), atrial septal defect (ASD),
pacemaker, inferior vena cava filter, or left atrial appendage closure device