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Updated: Feb 10, 2026
Optimized Management of Endovascular Treatment for Acute Ischemic Stroke
Published on: January 18, 2018
Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA
S Claiborne Johnston1, J Donald Easton1, Mary Farrant1
1From the Dean's Office, Dell Medical School, University of Texas at Austin, Austin (S.C.J.); the Department of Neurology, University of California, San Francisco, San Francisco (J.D.E., M.F., A.S.K.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B.); the Division of Clinical Research, National Institute of Neurological Disorders and Stroke, Bethesda (R.A.C.), and Emmes, Rockville (A.S.L.) - both in Maryland; and the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.J.E., Y.Y.P.).
Insights
Combination therapy with clopidogrel and aspirin reduced recurrent stroke risk after minor ischemic stroke or TIA. However, this approach also increased the risk of major hemorrhage compared to aspirin alone.
Area of Science:
- Neurology
- Cardiology
- Clinical Trials
Background:
- Combination antiplatelet therapy with clopidogrel and aspirin is investigated for reducing recurrent stroke risk post-minor ischemic stroke or transient ischemic attack (TIA).
- Previous studies in Chinese populations indicated a reduced risk of recurrent stroke with this combination therapy.
- This international trial aimed to validate these findings in a diverse patient cohort.
Purpose of the Study:
- To evaluate the efficacy and safety of combination clopidogrel and aspirin therapy compared to aspirin alone in patients with minor ischemic stroke or high-risk TIA.
- To determine the impact of this combination on the rate of major ischemic events and major hemorrhage within 90 days.
Main Methods:
- A randomized trial involving 4881 patients across 269 international sites.
- Patients received either clopidogrel (loading dose 600 mg, then 75 mg/day) plus aspirin (50-325 mg/day) or aspirin alone.
- The primary efficacy outcome was a composite of ischemic stroke, myocardial infarction, or ischemic vascular death at 90 days.
Main Results:
- The trial was halted early due to observed benefits and risks.
- Combination therapy showed a reduced risk of major ischemic events (5.0% vs. 6.5%, HR 0.75, P=0.02).
- However, combination therapy also led to a higher risk of major hemorrhage (0.9% vs. 0.4%, HR 2.32, P=0.02).
Conclusions:
- Combination clopidogrel and aspirin therapy significantly lowers the risk of major ischemic events in patients with minor ischemic stroke or high-risk TIA.
- This benefit is counterbalanced by a significantly increased risk of major hemorrhage.
- The findings suggest a need for careful consideration of the risk-benefit profile in clinical practice.
Background:
Combination antiplatelet therapy with clopidogrel and aspirin may reduce the rate of recurrent stroke during the first 3 months after a minor ischemic stroke or transient ischemic attack (TIA). A trial of combination antiplatelet therapy in a Chinese population has shown a reduction in the risk of recurrent stroke. We tested this combination in an international population.
Methods:
In a randomized trial, we assigned patients with minor ischemic stroke or high-risk TIA to receive either clopidogrel at a loading dose of 600 mg on day 1, followed by 75 mg per day, plus aspirin (at a dose of 50 to 325 mg per day) or the same range of doses of aspirin alone. The dose of aspirin in each group was selected by the site investigator. The primary efficacy outcome in a time-to-event analysis was the risk of a composite of major ischemic events, which was defined as ischemic stroke, myocardial infarction, or death from an ischemic vascular event, at 90 days.
Results:
A total of 4881 patients were enrolled at 269 international sites. The trial was halted after 84% of the anticipated number of patients had been enrolled because the data and safety monitoring board had determined that the combination of clopidogrel and aspirin was associated with both a lower risk of major ischemic events and a higher risk of major hemorrhage than aspirin alone at 90 days. Major ischemic events occurred in 121 of 2432 patients (5.0%) receiving clopidogrel plus aspirin and in 160 of 2449 patients (6.5%) receiving aspirin plus placebo (hazard ratio, 0.75; 95% confidence interval [CI], 0.59 to 0.95; P=0.02), with most events occurring during the first week after the initial event. Major hemorrhage occurred in 23 patients (0.9%) receiving clopidogrel plus aspirin and in 10 patients (0.4%) receiving aspirin plus placebo (hazard ratio, 2.32; 95% CI, 1.10 to 4.87; P=0.02).
Conclusions:
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. (Funded by the National Institute of Neurological Disorders and Stroke; POINT ClinicalTrials.gov number, NCT00991029 .).
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