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

Jul 03, 2019
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
National Institute of Neurological Disorders and Stroke
Date Published:
06/26/2019
Date Updated:
07/03/2019
Original Posted Date:
07/19/2018
References

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).

From 0 to 21 days, the risk of major ischemic events from clopidogrel plus aspirin versus placebo plus aspirin was hazard ratio (HR) 0.65 (p = 0.0015).

From 22 to 90 days, the risk of major ischemic events from clopidogrel plus aspirin versus placebo plus aspirin was HR 1.38 (p = 0.24).

Major hemorrhage occurred at a low, but constant rate over 90 days.

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 1,000 patients treated with this regimen, 15 ischemic events would be prevented at the cost of five excess major hemorrhages.

Subanalysis revealed that treatment for 21 days maximized benefit, while reducing harm. This is similar to the net benefit observed in the CHANCE trial (21 days of treatment).

References:

Johnston SC, Elm JJ, Easton JD, et al., on behalf of the POINT and Neurological Emergencies Treatment Trials Network Investigators. Time Course for Benefit and Risk of Clopidogrel and Aspirin After Acute Transient Ischemic Attack and Minor Ischemic Stroke: A Secondary Analysis From the POINT Randomized Trial. Circulation 2019;Jun 26:[Epub ahead of print].

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;379:215-25.

Editorial: Grotta JC. Antiplatelet Therapy After Ischemic Stroke or TIA. N Engl J Med 2018;379:291-2.

Keywords: Anticoagulants, 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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