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#291 Early dual antiplatelet therapy after minor stroke: Does it take two to tango?

In acute non-cardioembolic minor ischemic stroke or transient ischemic attack, does adding a second antiplatelet to ASA reduce recurrent stroke?

Compared to ASA alone, clopidogrel plus ASA reduced the risk of stroke from 8.2% to 5.5% but increased the risk of major bleeds from 0.6% to 1.2% at 21 days. Continuing clopidogrel beyond 21 days increased major bleeds without reducing strokes. There is no evidence that ticagrelor is more efficacious in reducing stroke than clopidogrel.

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  • Clopidogrel + ASA versus ASA: Time analysis from meta-analysis1 of 3 randomized controlled trials (RCTs), 10,447 patients:
    • Clopidogrel (300-600mg on day 1, then 75mg/day) plus ASA within 12-24 hours of onset of minor ischemic stroke or high-risk TIA versus ASA alone for 21-90 days, followed by single antiplatelet.
    • At 21 days:
      • Ischemic stroke: 5.5% versus 8.2% (ASA), number needed to treat (NNT)=38.
      • Major bleed: 1.2% versus 0.6% (ASA) (number needed to harm [NNH]=167)
    • On days 22-90:1,2 
      • Ischemic stroke: No difference.
      • Major bleed: 0.6% versus 0.3% (ASA), NNH=334.
  • Ticagrelor + ASA versus ASA: One RCT, 11,016 patients:3
    • Started ticagrelor (180mg on day 1, then 90mg twice daily) plus ASA within 24 hours of mild-moderate ischemic stroke or TIA versus ASA alone, continued for 30 days.
      • Ischemic stroke: Ticagrelor + ASA 5.0%, ASA 6.3%, NNT=84.
      • Moderate-severe bleed: 0.65% versus 0.2%, NNH~200
        • Intracranial hemorrhage: 0.36% versus 0.11%, NNH~330.
  • No significant differences in disability or death between dual and single antiplatelet.1
  • “Minor” stroke defined based on the National Institutes of Health Stroke Scale ≤3-5.1-4
  • Cardioembolic strokes (e.g. related to atrial fibrillation) are treated differently.5
  • Recurrent stroke risk highest within ~2 weeks of event.1,2,4
    • Guidelines recommend clopidogrel + ASA for 21 days in patients with acute non-cardioembolic minor ischemic stroke.5
  • Clopidogrel or ticagrelor alone have similar efficacy to ASA alone in minor-moderate ischemic non-cardioembolic stroke.6,7
  • In acute coronary syndromes, ticagrelor + ASA causes more major bleeding and dyspnea (NNH 16) than clopidogrel + ASA.8
  • Costs per 90 days: ASA $5, clopidogrel $40, ticagrelor $320.9

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  • Adrienne J Lindblad BSP ACPR PharmD
  • Jennifer Potter MD CCFP
  • Ricky D. Turgeon BSc(Pharm) ACPR PharmD

1. Hao, Tampi, O’Donnell M, et al. BMJ 2018; 363:k5108.

2. Johnston SC, Elm JJ, Easton JD, et al. Circulation 2019; 140:658-64.

3. Johnston SC, Amarenco P, Denison H, et al. New Engl J Med 2020; 383:207-17.

4. Pan Y, Jing J, Chen W, et al. Neurology 2017; 88:1906-11.

5. Powers WJ, Rabinstein AA, Ackerson T, et al. Stroke 2019; 50:e344-e418.

6. Lindblad AJ, Allan GM. Anti-platelets after stroke: Are two better than one? Tools for Practice online publication #109. Published March 17, 2014. Available at: Accessed May 20, 2021.

7. Johnston SC, Amarenco P, Albers GW, et al. N Engl J Med 2016; 375:35-43.

8. Wallentin L, Becker RC, Budaj A, et al. N Engl J Med 2009; 361:1045-57.

9. Alberta College of Family Physicians Price Comparison of Commonly Prescribed Pharmaceuticals in Alberta 2019. [accessed 2021 Jan 19]

Authors do not have any conflicts of interest to declare.