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


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


BOTTOM LINE
RÉSULTAT FINAL
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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EVIDENCE
DONNÉES PROBANTES
  • 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
Context
  • “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


karen day June 1, 2021

Good info to have

Ryan Mitchell June 1, 2021

Helpful article

Gilbert Bretecher June 6, 2021

new knowledge that Clopidogrel is more effective than Ticraglor for this condition

Steven Hobson July 5, 2021

excellent

Fanny Hersson-Edery July 8, 2021

I would like to see ASA versus clopidogrel as single antiplatelet therapy compared in efficacy of reducing stroke /TIA over longer periods of time. Some of my patients stay on clopidogrel for years and would like to know whether and when to stop antiplatelet therapy

Nidhi Pandey July 18, 2021

really helpful as we see alot of tia in GP land


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

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: https://gomainpro.ca/wp-content/uploads/tools-for-practice/1397843680_20140317_084605.pdf 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. https://acfp.ca/wp-content/uploads/2019/02/ACFPPricingDoc2019.pdf [accessed 2021 Jan 19]

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.