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Am Fam Physician. 2022;105(5):online

Clinical Question

What is the balance of benefits and harms for dual antiplatelet therapy compared with monotherapy for the secondary prevention of ischemic stroke?

Bottom Line

For patients with minor stroke or transient ischemic attack (TIA), dual antiplatelet therapy with aspirin plus clopidogrel (Plavix) for up to 30 days reduces the likelihood of subsequent stroke (number needed to treat = 50) more than aspirin monotherapy, with a small increase in the risk of major hemorrhage (number needed to harm = 500). A longer duration of therapy increases the risk of harm without increasing the likelihood of benefit. (Level of Evidence = 1a)


The authors identified randomized trials that compared dual antiplatelet therapy with monotherapy, started within three days of the index stroke or TIA. In some cases, the researchers were able to get data for the subset of patients who were randomized within three days from studies in which longer intervals were allowed between stroke and randomization. The search was comprehensive, and the analysis was methodologically sound. The final analysis included 17 studies with a total of 27,358 patients. The mean age of participants was 65 years, approximately two-thirds were men, and most studies targeted patients with minor ischemic stroke or TIA. The studies were assessed to be at low risk of bias. Monotherapy was aspirin in 15 studies and clopidogrel in two studies. The most common dual antiplatelet therapy regimen was aspirin plus clopidogrel. The largest study (THALES) compared aspirin alone with aspirin plus ticagrelor (Brilinta); because of the size of the study, the authors performed sensitivity analyses with and without this trial. Using dual antiplatelet therapy instead of monotherapy for 30 days or less resulted in 20 fewer strokes (number needed to treat = 50) and two more major hemorrhages (number needed to harm = 500) per 1,000 patients. The likelihood of major hemorrhage was the same when the THALES trial was excluded, although there was no longer a significant difference in the risk of hemorrhage between the aspirin and dual antiplatelet therapy groups. The authors stratified the analysis by treatment of more than 30 days or 30 days or less. Although the benefit was similar for a treatment duration of up to 30 days, the risk of hemorrhage was greater with a longer duration of therapy.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Setting: Outpatient (any)

Reference: Trifan G, Gorelick PB, Testai FD. Efficacy and safety of using dual versus monotherapy antiplatelet agents in secondary stroke prevention: systematic review and meta-analysis of randomized controlled clinical trials. Circulation. 2021;143(25):2441–2453.

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.

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