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P2Y12 inhibitors plus aspirin for acute treatment and secondary prevention in minor stroke and high-risk transient ischemic attack: A systematic review and meta-analysis

  • Author Footnotes
    1 Fulvio Pomero and Eleonora Galli were co-first authors.
    Fulvio Pomero
    Footnotes
    1 Fulvio Pomero and Eleonora Galli were co-first authors.
    Affiliations
    Department of Internal Medicine, Michele and Pietro Ferrero Hospital, Via Tanaro 7, 12060 Verduno, CN, Italy
    Search for articles by this author
  • Author Footnotes
    1 Fulvio Pomero and Eleonora Galli were co-first authors.
    Eleonora Galli
    Correspondence
    Corresponding author at: University of Turin, Department of Internal Medicine, Michele and Pietro Ferrero Hospital, Via Tanaro 7, 12060 Verduno, CN, Italy.
    Footnotes
    1 Fulvio Pomero and Eleonora Galli were co-first authors.
    Affiliations
    Department of Internal Medicine, Michele and Pietro Ferrero Hospital, Via Tanaro 7, 12060 Verduno, CN, Italy

    Department of Internal Medicine, University of Turin, Corso Dogliotti 14, 10126 Torino, Italy
    Search for articles by this author
  • Marta Bellesini
    Affiliations
    Department of Medicine and Surgery, Research Center on Thromboembolic Disorders and Antithrombotic Therapies, University of Insubria, Viale Luigi Borri 57, 21100 Varese, Italy
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  • Lorenzo Maroni
    Affiliations
    Department of General Medicine, Hypertension Dyslipidemia and Cardiovascular Risk Clinic, ASST Valle Olona, Sant'Antonio Abate Hospital, Via Eusebio Pastori, 21013 Gallarate, VA, Italy

    Ospedale di Circolo, Via Arnaldo da Brescia 1, 21052 Busto Arsizio, VA, Italy
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  • Alessandro Squizzato
    Affiliations
    Department of Medicine and Surgery, Research Center on Thromboembolic Disorders and Antithrombotic Therapies, University of Insubria, Viale Luigi Borri 57, 21100 Varese, Italy
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  • Author Footnotes
    1 Fulvio Pomero and Eleonora Galli were co-first authors.
Published:March 21, 2022DOI:https://doi.org/10.1016/j.ejim.2022.03.017

      Highlights

      • This paper corroborates the role of dual antiplatelet therapy (DAPT) both for acute treatment and secondary prevention of non-cardioembolic minor ischemic stroke and high-risk TIA.
      • The early administration (within 24 h from symptoms onset) of a P2Y12 inhibitor plus aspirin showed an absolute risk reduction of stroke recurrence about 2% and an absolute risk increase of major bleeding about 0.4%.
      • There was apparently no correlation between therapy duration and bleeding risk, differently from what previously obtained from other studies, probably due to association of ticagrelor plus aspirin.
      • The early use of DAPT reduces functional disability, compared to aspirin alone.
      • It is possible to hypothesize a personalization of therapy based on the clinical presentation severity and the bleeding risk profile of patients.

      Abstract

      Background

      Aspirin is a cornerstone of preventive treatment for stroke recurrence, but during the last few years the role of dual antiplatelet therapy (DAPT) is much more emerging.

      Objective

      This systematic review aimed to compare early use of P2Y12 inhibitors (clopidogrel/ticagrelor) plus aspirin to aspirin alone for acute treatment and secondary prevention in acute non-cardioembolic minor ischemic stroke or TIA.

      Methods

      A systematic search on MEDLINE and EMBASE was performed. Treatment effects were estimated with RRs and 95% CI. We used RevMan 5.4 for data analyses. We assessed methodological quality of selected studies according to Rob2 tools and quality of evidence with GRADE approach.

      Results

      Four RCTs were included, enrolling 21,459 patients. Compared to aspirin alone, DAPT was superior in reducing stroke recurrence (RR 0.74, 95% CI 0.67–0.82, P <0.00001, absolute risk difference by 2%, NNT 50) and disabling stroke defined as mRS>2 (RR 0.84, 95% CI 0.75–0.95, P = 0.004), with no impact on all causes of mortality (RR 1.30, 95% CI 0.90–1.89, P = 0.16). An increased risk of major bleeding was emerged (RR 2.54, 95% CI 1.65–3.92, P <0.0001, absolute risk difference by 0,4%, NNH 250), in particular with ticagrelor, but there was no correlation between therapy duration and bleeding risk, as appeared from one-month (RR 3.06, 95% CI 1.64 to 5.69) and three-month (RR 2.09, 95% CI 1.18 to 3.69) follow-up analysis.

      Conclusions

      Early administration of P2Y12 inhibitors plus aspirin in patients with acute non-cardioembolic minor ischemic stroke or TIA reduced the incidence of ischemic stroke recurrence, impacting more significantly than the increased bleeding risk and influencing patients’ quality of life by reducing disabling stroke.

      Keywords

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