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

Contribution To Literature:

The POINT trial showed that clopidogrel plus aspirin reduced ischemic events; however, it increased major bleeding events.

Description:

The goal of the trial was to evaluate clopidogrel plus aspirin compared with placebo plus aspirin among patients with minor stroke or high-risk transient ischemic attack (TIA). An earlier study had suggested that dual antiplatelet therapy may be beneficial when given for 21 days after stroke or TIA.

Study Design

  • Randomized
  • Parallel
  • Stratified

Patients with minor stroke or high-risk TIA were randomized to clopidogrel plus aspirin (n = 2,432) versus aspirin alone (n = 2,449). Clopidogrel was given as a loading dose of 600 mg, followed by 75 mg daily. Aspirin dose ranged from 50 to 325 mg daily.

  • Total number of enrollees: 4,881
  • Duration of follow-up: 90 days
  • Mean patient age: median 65 years
  • Percentage female: 45%

Inclusion criteria:

  • Minor stroke or high-risk TIA
  • At least 18 years of age
  • No intracranial bleeding by head computed tomography

Exclusion criteria:

  • Received thrombolytic therapy within the last week
  • Candidates for thrombolysis, endovascular therapy, or endarterectomy
  • Use of antiplatelet therapy or anticoagulation therapy
  • Contraindication to aspirin or clopidogrel
  • Use of a nonsteroidal anti-inflammatory drug for >7 days during the trial period

Principal Findings:

The primary efficacy outcome, cardiovascular death, stroke, or myocardial infarction, occurred in 5.0% of the clopidogrel plus aspirin group compared with 6.5% of the placebo plus aspirin group (p = 0.02).

The primary safety outcome, major hemorrhage (symptomatic intracranial hemorrhage, intraocular bleeding causing vision loss, transfusion of ≥2 units of red cells or an equivalent amount of whole blood, hospitalization or prolongation of an existing hospitalization, or death due to hemorrhage), occurred in 0.9% of the clopidogrel plus aspirin group compared with 0.4% of the placebo plus aspirin group (p = 0.02).

Interpretation:

Among patients with minor ischemic stroke or high-risk TIA, clopidogrel plus aspirin compared with placebo plus aspirin was associated with a reduction in ischemic events, but an increase in major hemorrhage. The investigators estimated that for every 100 patients treated with this regimen, 15 ischemic events would be prevented at the cost of five excess major hemorrhages. The longer treatment duration (90 days) in this trial may have contributed to the harm, which was not observed in the CHANCE trial (21 days of treatment).

References:

Johnston SC, Easton JD, Farrant M, et al., on behalf of the POINT Investigators. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med 2018;May 16:[Epub ahead of print].

Editorial: Grotta JC. Antiplatelet Therapy After Ischemic Stroke or TIA. N Engl J Med 2018;May 16:[Epub ahead of print].

Clinical Topics: Prevention

Keywords: Aspirin, Brain Ischemia, Hemorrhage, Intracranial Hemorrhages, Ischemic Attack, Transient, Myocardial Infarction, Platelet Aggregation Inhibitors, Primary Prevention, Secondary Prevention, Stroke, Vascular Diseases


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