Clopidogrel With Aspirin in Acute Minor Stroke or Transient Ischemic Attack

Study Questions:

What is the benefit of clopidogrel in patients with acute minor stroke or transient ischemic attacks (TIAs)?


The authors performed a randomized, double-blind, placebo-controlled trial at 114 centers in China, which assigned 5,170 patients within 24 hours after the onset of minor ischemic stroke (National Institutes of Health stroke scale of 3 or less) or high-risk TIA to combination therapy with clopidogrel and aspirin or aspirin alone. Combination therapy patients received clopidogrel at an initial dose of 300 mg, followed by 75 mg/day for 90 days, plus aspirin at a dose of 75 mg/day for the first 21 days, while the control arm received placebo plus aspirin (75 mg/day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75-300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to-treat analysis. Treatment differences were assessed with the use of a Cox proportional-hazards model, with study center as a random effect.


The median time from the onset of the qualifying minor stroke or TIA to randomization was 13 hours. Dual antiplatelet therapy was associated with a reduction in stroke (8.2% vs. 11.7%; hazard ratio, 0.68; 95% confidence interval, 0.57-0.81; p < 0.001). There was no difference in moderate or severe hemorrhage, which occurred in seven patients (0.3%) in the clopidogrel-aspirin group and in eight (0.3%) in the aspirin group (p = 0.73). The rate of hemorrhagic stroke was similar (0.3%) in both the arms. Overall bleeding trends were nonsignificantly higher in the dual antiplatelet therapy arm (2.3% vs. 1.6%, p = 0.09).


Among patients with TIA or minor stroke 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.


This study demonstrates a clinically relevant reduction in recurrent stroke with clopidogrel in patients with small strokes or TIAs. These results differ from prior studies and may relate to the fact that the investigators restricted enrollment to patients with minor stroke and those presenting early after symptom onset. Most of the events in the placebo arm occurred early after randomization, and the benefit of clopidogrel was evident in the first few days. Based on the results of this study, clopidogrel and aspirin should be initiated early in patients with minor stroke or TIAs.

Keywords: Stroke, China, Intracranial Hemorrhages, Ischemic Attack, Transient, Proportional Hazards Models, National Institutes of Health (U.S.), Ticlopidine

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