Patient-Oriented Evidence That Matters

Short-Term Clopidogrel Plus Aspirin Prevents Second Ischemic Stroke Better Than Aspirin Alone


Am Fam Physician. 2019 Aug 15;100(4):249.

Clinical Question

Does clopidogrel (Plavix) add benefit to aspirin treatment in patients with acute minor ischemic stroke or transient ischemic attack?

Bottom Line

Combined treatment with clopidogrel and aspirin, started within 24 hours of the first event, will decrease the likelihood of a recurrent stroke in an additional 2% of patients compared with aspirin alone, with a slight increase in the risk of extracranial bleeding. The greatest additional benefit is in the first 10 days with little additional benefit after 21 days of combined treatment. (Level of Evidence = 1a)


The authors searched several databases, including the Cochrane Central Register of Controlled Trials and reference lists of retrieved studies. They included studies that enrolled patients with a diagnosis of an acute minor ischemic stroke or high-risk transient ischemic attack for whom treatment was started within three days. Two researchers independently abstracted data from the studies and evaluated study quality. They identified three high-quality studies of 10,447 patients. When started within 24 hours of symptoms, combination treatment with clopidogrel and aspirin, compared with either treatment alone, had no additional effect on reducing all-cause mortality but reduced the risk of non-fatal recurrent stroke by 1.9% (a reduction of 20 per 1,000 patients treated). Stroke reduction benefit was most prominent in the first 10 days of treatment with the combination; there was little additional benefit after 21 days. The likelihood of major extracranial bleeding was slightly higher with the combination (0.2% absolute increase).

Study design: Systematic review

Funding source: Self-funded or unfunded

Setting: Various (meta-analysis)

Reference: Hao Q, Tampi M, O'Donnell M, et al. Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis. BMJ. 2018;363:k5108.

Editor's Note: Dr. Ebell is Deputy Editor for Evidence-Based Medicine for AFP and cofounder and Editor-in-Chief of Essential Evidence Plus, published by Wiley-Blackwell. Dr. Shaughnessy is an Assistant Medical Editor for AFP.


POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see http://www.essentialevidenceplus.com/product/ebm_loe.cfm?show=oxford.

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This series is coordinated by Sumi Sexton, MD, Editor-in-Chief.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.



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