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Evevident
Original paper
2018NEJMNeurology

POINT

Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA

RCTSecondary stroke prevention

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Overview

In minor stroke/high-risk TIA, clopidogrel plus aspirin reduced major ischemic events but increased major hemorrhage.

Clinical takeaway

POINT confirmed DAPT benefit in a broader international population but clarified the bleeding tradeoff, supporting short-duration therapy in selected patients.

Key result

Major ischemic events were lower with DAPT (5.0% vs 6.5%; HR 0.75), but major hemorrhage was higher.

Practice impact

Use short-course DAPT after minor stroke/high-risk TIA when bleeding risk is acceptable.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

4,881

Follow-up

90 days.

Geography

Multinational

Clinical question

Does clopidogrel plus aspirin reduce ischemic events after minor stroke or high-risk TIA, and what is the bleeding tradeoff?

Population

  • Patients with minor ischemic stroke (NIHSS <=3) or high-risk TIA treated within 12 hours of onset.

Intervention

Clopidogrel (600 mg load, then 75 mg daily) plus aspirin.

Comparator

Aspirin alone.

Primary outcome

Composite of major ischemic events (ischemic stroke, MI, or death from ischemic vascular causes) at 90 days.

Clopidogrel plus aspirin reduced major ischemic events after minor stroke or high-risk TIA but roughly doubled major hemorrhage.

Hazard ratio / 0.75 / CI 95% CI 0.59-0.95 / p=0.02

Key results

  • Major ischemic events: 5.0% with DAPT vs 6.5% with aspirin; HR 0.75 (95% CI 0.59-0.95; p=0.02).
  • Major hemorrhage: 0.9% with DAPT vs 0.4% with aspirin; HR 2.32 (95% CI 1.10-4.87; p=0.02).
  • Ischemic benefit was concentrated in the first week, while excess bleeding accrued later, supporting a shorter (~21-day) DAPT course.

Harms

  • Major hemorrhage was increased with DAPT (0.9% vs 0.4%; HR 2.32).
  • The bleeding excess accumulated beyond the first week, which is why guidelines favor limiting DAPT to about 21 days.

Clinical Use

When to cite

  • When using short-course dual antiplatelet therapy after minor stroke or high-risk TIA and weighing early ischemic benefit against bleeding risk.

Practice impact

  • Use short-course DAPT after minor stroke/high-risk TIA when bleeding risk is acceptable.

Applicability

  • Most applicable to patients with minor ischemic stroke (NIHSS <=3) or high-risk TIA who can start treatment within 12-24 hours.

Limitations

  • Bleeding risk rises with longer DAPT; POINT used 90 days whereas the excess harm supports a shorter course.
  • Does not apply to large strokes, cardioembolic stroke needing anticoagulation, or patients recently treated with thrombolysis without guideline review.

Common misinterpretations

  • POINT and CHANCE together support DAPT for about 21 days, not 90 days; the longer POINT regimen added bleeding without added ischemic benefit.
  • The net benefit is greatest when DAPT is started early and stopped after the first few weeks.

Related evidence

CHANCE - Similar Question

Citation

Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med. 2018;379(3):215-225. doi:10.1056/NEJMoa1800410

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.