Advertisement

Meta-Analysis of Usefulness of Antiplatelet Therapy in Ischemic Stroke or Transient Ischemic Attack

      The efficacy of early administration of dual antiplatelet therapy (DAPT) for secondary prevention after acute ischemic stroke or transient ischemic attack (TIA) is uncertain. This systematic review and meta-analysis compares the safety and efficacy of early administration (<24 hours) of DAPT (using either clopidogrel or ticagrelor with aspirin) versus single antiplatelet therapy (SAPT; aspirin alone) in acute non-cardioembolic ischemic stroke or TIA, incorporating data from large randomized controlled trials. Published trials fulfilling our criteria were identified from an electronic search of MEDLINE, with key words including: “clopidogrel or ticagrelor”, “aspirin”, “ischemic stroke”, “transient ischemic attack”, and “randomized controlled trial”. Included were 3 randomized controlled trials of 21,067 patients assessing early administration (<24 hours from symptom onset) of DAPT versus SAPT in non-cardioembolic acute ischemic stroke or TIA. Our efficacy outcomes were ischemic stroke and all-cause mortality. Our safety outcome was severe bleeding. We performed a meta-analysis to pool results with a hierarchical Bayesian random-effects model. Dual antiplatelet therapy significantly reduced the risk of ischemic stroke (hazard ratio [HR], 0.73; 95% credible interval [CrI]: 0.54, 0.97), while increasing the risk of severe bleeding (HR, 2.48; 95% CrI: 1.07, 5.26). There was a non-significant numerical trend toward increased mortality with DAPT (HR, 1.29; 95% CrI: 0.73, 2.23). These observations were robust under the sensitivity analysis. In the present systematic review and meta-analysis of randomized controlled trials, DAPT reduced the risk of ischemic stroke at the cost of an increase in severe bleeding. Additional trials examining the ideal timing of DAPT administration are needed to thoroughly investigate the role, if any, of routine DAPT in patients with non-cardioembolic ischemic stroke or high-risk TIA.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Virani SS
        • Alonso A
        • Aparicio HJ
        • Benjamin EJ
        • Bittencourt MS
        • Callaway CW
        • Carson AP
        • Chamberlain AM
        • Cheng S
        • Delling FN
        • Elkind MSV
        • Evenson KR
        • Ferguson JF
        • Gupta DK
        • Khan SS
        • Kissela BM
        • Knutson KL
        • Lee CD
        • Lewis TT
        • Liu J
        • Loop MS
        • Lutsey PL
        • Ma J
        • Mackey J
        • Martin SS
        • Matchar DB
        • Mussolino ME
        • Navaneethan SD
        • Perak AM
        • Roth GA
        • Samad Z
        • Satou GM
        • Schroeder EB
        • Shah SH
        • Shay CM
        • Stokes A
        • VanWagner LB
        • Wang NY
        • Tsao CW
        • On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
        Heart disease and stroke statistics-2021 update: a report from the American Heart Association.
        Circulation. 2021; 143: e254-e743
        • Hackam DG
        • Spence JD.
        Antiplatelet therapy in ischemic stroke and transient ischemic attack.
        Stroke. 2019; 50: 773-778
        • Wang Y
        • Wang Y
        • Zhao X
        • Liu L
        • Wang D
        • Wang C
        • Wang C
        • Li H
        • Meng X
        • Cui L
        • Jia J
        • Dong Q
        • Xu A
        • Zeng J
        • Li Y
        • Wang Z
        • Xia H
        • Johnston SC
        • CHANCE Investigators
        Clopidogrel with aspirin in acute minor stroke or transient ischemic attack.
        N Engl J Med. 2013; 369: 11-19
        • Johnston SC
        • Easton JD
        • Farrant M
        • Barsan W
        • Conwit RA
        • Elm JJ
        • Kim AS
        • Lindblad AS
        • Palesch YY
        • Clinical Research Collaboration, Neurological Emergencies Treatment Trials Network, and the POINT Investigators
        Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA.
        N Engl J Med. 2018; 379: 215-225
        • Johnston SC
        • Amarenco P
        • Denison H
        • Evans SR
        • Himmelmann A
        • James S
        • Knutsson M
        • Ladenvall P
        • Molina CA
        • Wang Y
        • THALES Investigators
        Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA.
        N Engl J Med. 2020; 383: 207-217
        • Hutton B
        • Salanti G
        • Caldwell DM
        • Chaimani A
        • Schmid CH
        • Cameron C
        • Ioannidis JP
        • Straus S
        • Thorlund K
        • Jansen JP
        • Mulrow C
        • Catala-Lopez F
        • Gotzsche PC
        • Dickersin K
        • Boutron I
        • Altman DG
        • Moher D.
        The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations.
        Ann Intern Med. 2015; 162: 777-784
        • Powers WJ
        • Rabinstein AA
        • Ackerson T
        • Adeoye OM
        • Bambakidis NC
        • Becker K
        • Biller J
        • Brown M
        • Demaerschalk BM
        • Hoh B
        • Jauch EC
        • Kidwell CS
        • Leslie-Mazwi TM
        • Ovbiagele B
        • Scott PA
        • Sheth KN
        • Southerland AM
        • Summers DV
        • Tirschwell DL.
        Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.
        Stroke. 2019; 50: e344-e418
        • Diener HC
        • Cunha L
        • Forbes C
        • Sivenius J
        • Smets P
        • Lowenthal A.
        European stroke prevention study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.
        J Neurol Sci. 1996; 143: 1-13
        • Halkes PH
        • van Gijn J
        • Kappelle LJ
        • Koudstaal PJ
        • Algra A
        • ESPRIT Study Group
        Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.
        Lancet. 2006; 367: 1665-1673
        • Dengler R
        • Diener HC
        • Schwartz A
        • Grond M
        • Schumacher H
        • Machnig T
        • Eschenfelder CC
        • Leonard J
        • Weissenborn K
        • Kastrup A
        • Haberl R
        • investigators for the EARLY
        Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset (EARLY trial): a randomised, open-label, blinded-endpoint trial.
        Lancet Neurol. 2010; 9: 159-166
        • GUSTO investigators
        An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction.
        N Engl J Med. 1993; 329: 673-682
        • Grant RL
        The uptake of Bayesian methods in biomedical meta-analyses: a scoping review (2005-2016).
        J Evid Based Med. 2019; 12: 69-75
        • Higgins JP
        • Thompson SG
        • Spiegelhalter DJ.
        A re-evaluation of random-effects meta-analysis.
        J R Stat Soc Ser A Stat Soc. 2009; 172: 137-159
        • Plummer M.
        JAGS: A program for analysis of Bayesian graphical models using Gibbs sampling.
        in: Proceedings of the 3rd International Workshop on Distributed Statistical Computing (DSC 2003), Vienna, Austria2003: 1-10
        • Hespanhol L
        • Vallio CS
        • Costa LM
        • Saragiotto BT.
        Understanding and interpreting confidence and credible intervals around effect estimates.
        Braz J Phys Ther. 2019; 23: 290-301
        • Diener HC
        • Hankey GJ.
        Primary and secondary prevention of ischemic stroke and cerebral hemorrhage: JACC focus seminar.
        J Am Coll Cardiol. 2020; 75: 1804-1818
        • Spiegelhalter DJ
        • Myles JP
        • Jones DR
        • Abrams KR
        Bayesian methods in health technology assessment: a review.
        Health Technol Assess. 2000; 4: 1-130