POINT

POINT: Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke

Sponsored by: NIH

Principal Investigator at BMC: J Rafael Romero, MD

Study duration: 90 days

Study drugs: Aspirin vs aspirin & 75mg clopidogrel QD (600mg/placebo loading dose; 81mg ASA site prescription)

Inclusion Criteria:

1. Neurologic deficit (based on history or exam) attributed to focal brain ischemia and EITHER:

• High risk TIA: Complete resolution of the deficit at the time of randomization AND ABCD² score >4

OR

• Minor ischemic stroke: residual deficit with NIHSS <3 at the time of randomization

2. Ability to randomize within 12 hours of time last known free of new ischemic symptoms.
3. Head CT or MRI ruling out hemorrhage or other pathology (i.e. vascular malformation, tumor, or abscess).
4. Ability to tolerate aspirin at a dose of 50-325 mg/day.

Exclusion Criteria:

1. Age <18 years.
2. TIA symptoms limited to isolated numbness, isolated visual changes, or isolated dizziness/vertigo.
3. A candidate for thrombolysis, endarterectomy or endovascular intervention, unless the subject declines both endarterectomy and endovascular intervention at the time of evaluation for eligibility.
4. Receipt of any intravenous or intra-arterial thrombolysis within 1 week prior to index event.
5. Gastrointestinal bleed or major surgery within 3 months prior to index event.
6. History of nontraumatic intracranial hemorrhage.
7. Clear indication for anticoagulation (e.g., warfarin, heparin) such as atrial fibrillation, mechanical heart valve, deep venous thrombosis, pulmonary embolism, antiphospholipid antibody syndrome, hypercoagulable state.
8. Qualifying  ischemic event induced by angiography or surgery.
9. Severe non-cardiovascular comorbidity with life expectancy <3 months.
10. Contraindication to clopidogrel or aspirin:
    • Known allergy
    • Severe renal (serum creatinine >2 mg/dL) or hepatic insufficiency (prior or concurrent diagnosis, with INR>1.5, or any resultant complication, such as variceal bleeding, encephalopathy, or icterus)
    • Hemostatic disorder or systemic bleeding in the past 3 months
    • Current thrombocytopenia (platelet count <100 x10⁹/l) or neutropenia/granulocytopenia (<1 x10⁹/l)
    • History of drug-induced hematologic or hepatic abnormalities
11. Anticipated requirement for long-term (>7 day) non-study antiplatelet drugs (e.g., dipyridamole, clopidogrel, ticlopidine), or NSAIDs affecting platelet function (such as prior vascular stent or arthritis).
12. At risk for pregnancy:  premenopausal or post menopausal woman within 12 months of last menses  without a negative pregnancy test or not committing to adequate birth control (e.g., oral contraceptive,  two methods of barrier birth control, or abstinence).
13. Ongoing treatment in another study of an investigational therapy, or treatment in such a study within the last 7 days. (and previous POINT study patient)

A prospective, randomized, double-blind, multicenter trial with the primary null hypothesis that, in patients with TIA or minor ischemic stroke treated with aspirin 50-325 mg/day, there is no difference in the event-free survival at 90 days in those treated with clopidogrel (600 mg loading dose then 75 mg/day) compared to placebo when therapy is initiated within 12 hours of onset.

N Engl J Med 2018; 379:215-225.

In patients with minor ischemic stroke or high-risk TIA, those who received a combination of clopidogrel and aspirin had a lower risk of major ischemic events but a higher risk of major hemorrhage at 90 days than those who received aspirin alone.