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Evevident
Original paper
2013NEJMNeurology

CHANCE

Clopidogrel with aspirin in acute minor stroke or transient ischemic attack

RCTSecondary stroke prevention

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Overview

In minor stroke/TIA treated within 24 hours, 21 days of aspirin plus 90 days of clopidogrel reduced recurrent stroke without increasing hemorrhage in the Chinese trial population.

Clinical takeaway

CHANCE supports early short-course DAPT after minor ischemic stroke or high-risk TIA, especially when started promptly.

Key result

Recurrent stroke at 90 days was lower with clopidogrel-aspirin (8.2% vs 11.7%; HR 0.68).

Practice impact

Short-course DAPT became standard for selected minor stroke/high-risk TIA patients.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

5,170

Follow-up

90 days.

Geography

China

Clinical question

Does early clopidogrel plus aspirin reduce recurrent stroke after minor stroke or high-risk TIA?

Population

  • Chinese patients with minor ischemic stroke (NIHSS <=3) or high-risk TIA treated within 24 hours of onset.

Intervention

Clopidogrel (300 mg load, then 75 mg daily) plus aspirin for 21 days, then clopidogrel alone through 90 days.

Comparator

Aspirin alone.

Primary outcome

Stroke (ischemic or hemorrhagic) at 90 days.

Short-course clopidogrel plus aspirin reduced recurrent stroke at 90 days without a significant increase in hemorrhage.

Hazard ratio / 0.68 / CI 95% CI 0.57-0.81 / p=<0.001

Key results

  • Stroke at 90 days: 8.2% with clopidogrel-aspirin vs 11.7% with aspirin; HR 0.68 (95% CI 0.57-0.81; p<0.001).
  • Moderate or severe hemorrhage occurred in 0.3% of each group, with no significant difference.
  • The benefit was concentrated in the first weeks after the event.

Harms

  • Moderate or severe hemorrhage did not differ between groups (0.3% vs 0.3%).
  • Any bleeding was slightly more frequent with dual antiplatelet therapy.

Clinical Use

When to cite

  • When starting early dual antiplatelet therapy after minor ischemic stroke or high-risk TIA, while limiting duration to the early high-risk period.

Practice impact

  • Short-course DAPT became standard for selected minor stroke/high-risk TIA patients.

Applicability

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

Limitations

  • Conducted entirely in China; higher CYP2C19 loss-of-function prevalence and different stroke mechanisms may affect generalizability.
  • DAPT was short-course (21 days), not indefinite.
  • Confirmed in a broader population by POINT, which also revealed the bleeding tradeoff of longer therapy.

Common misinterpretations

  • CHANCE does not support indefinite dual antiplatelet therapy; benefit comes from a brief early course.
  • The lack of excess bleeding partly reflects the short 21-day DAPT duration and a lower clopidogrel loading dose than POINT.

Related evidence

POINT - Similar Question

Citation

Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med. 2013;369(1):11-19. doi:10.1056/NEJMoa1215340

Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage.