A combined therapeutic strategy consisting of clopidogrel and aspirin may reduce the risk for major ischemic events in patients with minor ischemic stroke or high-risk transient ischemic attack (TIA), according to results from a randomized trial published in the New England Journal of Medicine.

The study investigators randomly assigned patients with minor ischemic stroke or high-risk TIA (ABCD2 scale score of ≥4) to either clopidogrel plus 50 to 325 mg/day aspirin (n=2432) or 50 to 325 mg/day aspirin only (n=2449). In the combined treatment group, patients received a loading clopidogrel dose of 600 mg on day 1 and a clopidogrel dose of 75 mg/day on subsequent days. The risk for a 90-day composite of major ischemic events (ie, ischemic stroke, myocardial infarction, or mortality related to an ischemic vascular event) made up the primary efficacy outcome.

At 90-day follow-up, the data and safety monitoring board halted the trial after it found that approximately 84% of patients had experienced both a lower risk and a higher risk for major ischemic events and major hemorrhage compared with aspirin only, respectively.

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Significantly fewer patients in the combined therapy regimen experienced a major ischemic event during follow-up compared with those in the aspirin-only group (5.0% vs 6.5%, respectively; hazard ratio, 0.75; 95% CI, 0.59-0.95; P =.02). The majority of these events were reported in the first week after the initial ischemic event.

Despite the reduction in major ischemic events among the clopidogrel plus aspirin group, these patients had significantly greater major hemorrhage rates compared with those receiving aspirin monotherapy (0.9% vs 0.4%, respectively; hazard ratio, 2.32; 95% CI, 1.10-4.87; P =.02).

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The findings from this study may not be generalizable to patients with cardioembolic stroke or moderate to severe stroke, as these patients were not represented in the analysis.

The majority of composite events of the primary outcome were ischemic strokes, and the investigators suggest that “the effect of dual antiplatelet treatment was attributable to a reduction in the rate of these strokes.”


Johnston SC, Easton JD, Farrant M, et al; for the Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA [published online May 16, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1800410