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European Society for Vascular Surgery (ESVS) 2023 Clinical Practice Guidelines on the Management of Atherosclerotic Carotid and Vertebral Artery Disease

  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Ross Naylor
    Correspondence
    Corresponding author. Leicester Vascular Institute, Glenfield Hospital, Leicester LE39QP, United Kingdom.
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Barbara Rantner
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Stefano Ancetti
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Gert J. de Borst
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Marco De Carlo
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Alison Halliday
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Stavros K. Kakkos
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Hugh S. Markus
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Dominick J.H. McCabe
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Henrik Sillesen
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Jos C. van den Berg
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Melina Vega de Ceniga
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Maarit A. Venermo
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    Frank E.G. Vermassen
    Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
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  • Author Footnotes
    b ESVS Guidelines Committee: George A. Antoniou (Manchester, UK), Frederico Bastos Goncalves (Lisbon, Portugal), Martin Bjorck (Uppsala, Sweden), Nabil Chakfe (Strasbourg, France), Raphael Coscas (Paris, France), Nuno V. Dias (Malmö, Sweden), Florian Dick (St Gallen, Switzerland), Robert J. Hinchliffe (Bristol, UK), Philippe Kolh (Liege, Belgium), Igor B. Koncar (Belgrade, Serbia), Jes S. Lindholt (Odense, Denmark), Barend M.E. Mees (Maastricht, the Netherlands), Timothy A. Resch (Copenhagen, Denmark), Santi Trimarchi (Milan, Italy), Riikka Tulamo (Helsinki, Finland), Christopher P. Twine (Bristol, UK), Anders Wanhainen (Uppsala, Sweden)
    ESVS Guidelines Committee
    Footnotes
    b ESVS Guidelines Committee: George A. Antoniou (Manchester, UK), Frederico Bastos Goncalves (Lisbon, Portugal), Martin Bjorck (Uppsala, Sweden), Nabil Chakfe (Strasbourg, France), Raphael Coscas (Paris, France), Nuno V. Dias (Malmö, Sweden), Florian Dick (St Gallen, Switzerland), Robert J. Hinchliffe (Bristol, UK), Philippe Kolh (Liege, Belgium), Igor B. Koncar (Belgrade, Serbia), Jes S. Lindholt (Odense, Denmark), Barend M.E. Mees (Maastricht, the Netherlands), Timothy A. Resch (Copenhagen, Denmark), Santi Trimarchi (Milan, Italy), Riikka Tulamo (Helsinki, Finland), Christopher P. Twine (Bristol, UK), Anders Wanhainen (Uppsala, Sweden)
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  • George A. Antoniou
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  • Frederico Bastos Goncalves
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  • Martin Bjorck
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  • Nabil Chakfe
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  • Raphael Coscas
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  • Nuno V. Dias
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  • Florian Dick
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  • Robert J. Hinchliffe
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  • Philippe Kolh
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  • Igor B. Koncar
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  • Jes S. Lindholt
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  • Barend M.E. Mees
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  • Timothy A. Resch
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  • Santi Trimarchi
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  • Riikka Tulamo
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  • Christopher P. Twine
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  • Anders Wanhainen
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  • Author Footnotes
    c ESVS Guideline Reviewers: Sergi Bellmunt-Montoya (Barcelona, Spain), Richard Bulbulia (Oxford, UK), R Clement Darling, III (New York, USA), Hans-Henning Eckstein (Munich, Germany), Athanasios Giannoukas (Larissa, Greece), Mark J.W. Koelemay (Amsterdam, the Netherlands), David Lindström (Uppsala, Sweden), Marc Schermerhorn (Boston, USA), David H. Stone (Dartmouth, USA)
    Document Reviewers
    Footnotes
    c ESVS Guideline Reviewers: Sergi Bellmunt-Montoya (Barcelona, Spain), Richard Bulbulia (Oxford, UK), R Clement Darling, III (New York, USA), Hans-Henning Eckstein (Munich, Germany), Athanasios Giannoukas (Larissa, Greece), Mark J.W. Koelemay (Amsterdam, the Netherlands), David Lindström (Uppsala, Sweden), Marc Schermerhorn (Boston, USA), David H. Stone (Dartmouth, USA)
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  • Sergi Bellmunt-Montoya
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  • Richard Bulbulia
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  • R Clement Darling III
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  • Hans-Henning Eckstein
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  • Athanasios Giannoukas
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  • Mark J.W. Koelemay
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  • David Lindström
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  • Marc Schermerhorn
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  • David H. Stone
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  • Author Footnotes
    a Guideline Writing Committee: Ross Naylor (Leicester, United Kingdom, chairperson), Barbara Rantner (Munich, Germany, co-chairperson), Stefano Ancetti (Bologna, Italy), Gert J. de Borst (Utrecht, Netherlands), Marco De Carlo (Pisa, Italy), Alison Halliday (Oxford, United Kingdom), Stavros K. Kakkos (Patras, Greece), Hugh S. Markus (Cambridge, United Kingdom), Dominick J.H. McCabe (Dublin, Ireland), Henrik Sillesen (Copenhagen, Denmark), Jos C. van den Berg (Lugano/Bern, Switzerland), Melina Vega de Ceniga (Osakidetza, Spain), Maarit A. Venermo (Helsinki, Finland), Frank E.G. Vermassen (Ghent, Belgium)
    b ESVS Guidelines Committee: George A. Antoniou (Manchester, UK), Frederico Bastos Goncalves (Lisbon, Portugal), Martin Bjorck (Uppsala, Sweden), Nabil Chakfe (Strasbourg, France), Raphael Coscas (Paris, France), Nuno V. Dias (Malmö, Sweden), Florian Dick (St Gallen, Switzerland), Robert J. Hinchliffe (Bristol, UK), Philippe Kolh (Liege, Belgium), Igor B. Koncar (Belgrade, Serbia), Jes S. Lindholt (Odense, Denmark), Barend M.E. Mees (Maastricht, the Netherlands), Timothy A. Resch (Copenhagen, Denmark), Santi Trimarchi (Milan, Italy), Riikka Tulamo (Helsinki, Finland), Christopher P. Twine (Bristol, UK), Anders Wanhainen (Uppsala, Sweden)
    c ESVS Guideline Reviewers: Sergi Bellmunt-Montoya (Barcelona, Spain), Richard Bulbulia (Oxford, UK), R Clement Darling, III (New York, USA), Hans-Henning Eckstein (Munich, Germany), Athanasios Giannoukas (Larissa, Greece), Mark J.W. Koelemay (Amsterdam, the Netherlands), David Lindström (Uppsala, Sweden), Marc Schermerhorn (Boston, USA), David H. Stone (Dartmouth, USA)

      Abbreviations and acronyms

      ACAS
      Asymptomatic Carotid Atherosclerosis Study
      ACE
      Aspirin and Carotid Endarterectomy Trial
      ACES
      Asymptomatic Carotid Emboli Study
      ACS
      Asymptomatic carotid stenosis
      ACSRS
      Asymptomatic Carotid Stenosis and Risk of Stroke Study
      ACST
      Asymptomatic Carotid Surgery Trial (1 & 2)
      ACT-1
      Asymptomatic Carotid Trial-1
      AHA
      American Heart Association
      APRx
      Antiplatelet therapy
      ARR
      Absolute risk reduction
      ARWMC
      Age related white matter change
      AF
      Atrial fibrillation
      BA
      Basilar artery
      BES
      Balloon expandable stent
      BMS
      Bare metal stent
      BMI
      Body mass index
      BMT
      Best medical therapy
      BP
      Blood pressure
      CA
      Carotid angioplasty
      CABG
      Coronary artery bypass graft
      CAD
      Coronary artery disease
      CAS
      Carotid artery stenting
      CAVATAS
      Carotid & Vertebral Artery Transluminal Angioplasty Study
      CaW
      Carotid web
      CCA
      Common carotid artery
      CCF
      Congestive cardiac failure
      CEA
      Carotid endarterectomy
      CCEA
      Conventional carotid endarterectomy
      CEMRA
      Contrast enhanced magnetic resonance angiography
      CETC
      Carotid Endarterectomy Trialists Collaboration
      CFA
      Common femoral artery
      CI
      Confidence Interval
      CNI
      Cranial nerve injury
      CNO
      Carotid near occlusion
      COMPASS
      Cardiovascular Outcomes for People Using Anticoagulation Strategies
      COPD
      Chronic obstructive pulmonary disease
      CoW
      Circle of Willis
      CPD
      Cerebral protection device
      CREST
      Carotid Revascularisation vs. Stenting Trial
      CSTC
      Carotid Stent Trialists Collaboration
      CT
      Computerised tomography
      CTA
      Computerised tomography angiography
      CVR
      Cerebral vascular reserve
      DAPT
      Dual antiplatelet therapy
      DBP
      Diastolic blood pressure
      DES
      Drug eluting stent
      DLS
      Dual layer stent
      DM
      Diabetes mellitus
      DOAC
      Direct oral anticoagulant
      DSA
      Digital subtraction angiography
      DUS
      Duplex ultrasound
      DWI
      Diffusion weighted imaging
      EAS
      European Atherosclerosis Society
      ECA
      External carotid artery
      ECEA
      Eversion carotid endarterectomy
      ECG
      Electrocardiogram
      EC-IC
      Extracranial intracranial
      ECST
      European Carotid Surgery Trial
      EEG
      Electroencephalography
      EJVES
      European Journal of Vascular and Endovascular Surgery
      ESC
      European Society of Cardiology
      ESH
      European Society of Hypertension
      ESO
      European Stroke Organisation
      ESVS
      European Society for Vascular Surgery
      EVA-3S
      Endarterectomy vs. Stenting in patients with Symptomatic Severe carotid Stenosis
      FLAIR
      Fluid attenuated inverse recovery
      FFT
      Free floating thrombus
      GA
      General anaesthesia
      GC
      Guidelines Committee
      GWC
      Guideline Writing Committee
      HDU
      High Dependency Unit
      HR
      Hazard ratio
      HRF
      High risk feature
      HS
      Hyperperfusion syndrome
      HTPR
      High on treatment platelet reactivity
      ICA
      Internal carotid artery
      ICH
      Intracerebral haemorrhage
      ICSS
      International Carotid Stenting Study
      IPH
      Intraplaque haemorrhage
      IA
      Innominate artery
      ISR
      In stent re-stenosis
      ITU
      Intensive therapy unit
      i.v.
      Intravenous
      JBA
      Juxtaluminal black area
      LAA
      Large artery atherosclerosis
      LDL-C
      Low density lipoprotein cholesterol
      LMWH
      Low molecular weight heparin
      LRA
      Locoregional anaesthesia
      MCA
      Middle cerebral artery
      MDT
      Multidisciplinary team
      MES
      Micro-embolic signals
      MI
      Myocardial infarction
      MRA
      Magnetic resonance angiography
      MRI
      Magnetic resonance imaging
      mRS
      Modified Rankin Score
      MT
      Mechanical thrombectomy
      NASCET
      North American Symptomatic Carotid Endarterectomy Trial
      NIBL
      New ischaemic brain lesion
      NIHSS
      National Institutes of Health Stroke Score
      OR
      Odds Ratio
      PAD
      Peripheral arterial disease
      PCA
      Posterior cerebral artery
      PCSK9
      Proprotein convertase subtilisin/kexin type 9
      PPI
      Proton pump inhibitor
      PSV
      Peak systolic velocity
      PTFE
      Polytetrafluoroethylene
      QC
      Quality control
      QIP
      Quality improvement programme
      RCT
      Randomised controlled trial
      rTPA
      Recombinant Tissue Plasminogen Activator
      RLN
      Recurrent laryngeal nerve
      RR
      Relative risk
      RRI
      Relative risk increase
      RRR
      Relative risk reduction
      SAPPHIRE
      Stenting & Angioplasty with Protection in Patients at High Risk for Endarterectomy
      SAMMPRIS
      Stenting & Aggressive Medical Management for Preventing Recurrent Stroke & Intracranial Stenosis
      SBP
      Systolic blood pressure
      SCS
      Symptomatic carotid stenosis
      SVS
      Society for Vascular Surgery (North America)
      SPACE
      Stent Protected Angioplasty vs. Carotid Endarterectomy
      SSEP
      Somatosensory evoked potentials
      TCD
      Transcranial Doppler
      TCAR
      Transcarotid artery revascularisation
      TFCAS
      Transfemoral carotid artery stenting
      TIA
      Transient ischaemic attack
      TOAST
      Trial of ORG 10172 in Acute Stroke Treatment
      TRA
      Transradial artery access
      TT
      Thrombolytic therapy
      UFH
      Unfractionated heparin
      USPSTF
      US Preventive Services Taskforce
      VACS
      Veterans Affairs Co-operative Study
      VA
      Vertebral artery
      VAST
      Vertebral Artery Stenting Trial
      VB
      Vertebrobasilar
      VISSIT
      Vitesse Intracranial Stent Study for Ischaemic Stroke Therapy
      VAST
      Vertebral Artery Ischaemia Stenting Trial
      VKA
      Vitamin K antagonist
      VQI
      Vascular Quality Initiative
      VSGNE
      The Vascular Surgery Group of New England

      What is new in the 2023 guidelines?

      Each section has been revised or rewritten and five new sections added: (i) management of free floating thrombus (section 4.13), (ii) management of carotid webs (section 4.14), (iii) management of symptomatic patients with an ipsilateral 50–99% carotid stenosis and atrial fibrillation (AF) (section 4.16), (iv) planning carotid interventions in anticoagulated patients (section 4.2.6), and (v) timing of carotid interventions in patients with acute ischaemic stroke undergoing thrombolysis (section 4.8). The 2023 European Society for Vascular Surgery (ESVS) carotid and vertebral guidelines also highlight similarities/discrepancies with the 2021 American Heart Association (AHA) guidelines on the management of stroke/transient ischaemic attack (TIA),
      • Kleindorfer D.O.
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      2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association.
      the 2021 European Stroke Organisation (ESO) guidelines on carotid endarterectomy (CEA) and carotid artery stenting (CAS),
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      European Stroke Organisation guideline on endarterectomy and stenting for carotid artery stenosis.
      the 2021 German-Austrian guidelines on the management of carotid disease,

      Eckstein HH, Kühnl A, Berkefeld J, Dörfler A, Kopp I, Langhoff R, et al. S3-Leitline zur Diagnostik, Therapie und Nachsorge der extracraniellen Carootisstenose Langfassung, Kurzfassung und Leitlinienreport. Available at: https://www.awmf.org/fileadmin/user_upload/Leitlinien/004_D_Ges_fuer_Gefaesschirurgie/004–028ke_extracranial-carotid-stenosis-diagnosis-treatment-aftercare_2021–04.pdf [Accessed 31 January 2022].

      and the 2021 Society for Vascular Surgery (SVS) guidelines on the management of patients with carotid and vertebral artery disease.
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      Society for Vascular Surgery Clinical Practice Guidelines for Management of Extracranial Cerebrovascular Disease.
      There are 133 recommendations, of which, 84 are unchanged, 11 have been “regraded” since 2017 and 38 are new. The 2023 ESVS guidelines benefit from 289 new references (240 published between 2017 and 2022), including 39 primary or secondary analyses from randomised controlled trials (RCTs),
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      Identification, prognosis and management of patients with carotid artery near occlusion.
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      Stroke prevention with the PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab added to statin in high-risk patients with stable atherosclerosis.
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      on behalf of the ACST-2 Collaborative Group. Second Asymptomatic Carotid Surgery Trial (ACST-2): a randomised comparison of carotid artery stenting vs carotid endarterectomy.
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      • et al.
      Effect of carotid endarterectomy on 20-year incidence of recorded dementia: a randomised trial.
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      for the EUREKA Investigators. Effect and safety of rosuvastatin in acute ischemic stroke.
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      • et al.
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      • et al.
      Ticagrelor versus aspirin in acute stroke or transient ischemic attack.
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      Clopidogrel and aspirin in acute ischaemic stroke and high-risk TIA.
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      Clopidogrel and aspirin after acute transient ischemic attack and minor ischemic stroke: a secondary analysis from the POINT randomized trial.
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      • Himmelman A.
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      • et al.
      on behalf of the THALES Investigators. Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA.
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      • et al.
      Periprocedural stroke and myocardial infarction as risks for long-term mortality in CREST.
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      Stenting for symptomatic vertebral artery stenosis: The Vertebral Artery Ischaemia Stenting Trial.
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      Carotid wallstent versus roadsaver stent and distal versus proximal protection on cerebral microembolization during carotid artery stenting.
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      71 systematic reviews and/or meta-analyses,
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      There is an expanded section on “best medical therapy” (BMT) in asymptomatic (section 3.1) and symptomatic patients (section 4.2). There are new sections on the role of combination antiplatelet therapy (APRx) in recently symptomatic patients (section 4.2.2.2), including the peri-operative period (sections 4.2.2.3 and 4.2.2.4); thresholds for treating hypertension (section 4.2.8); and targets for lipid lowering therapy (section 4.2.7.3). There is a rewritten section on the relationship between asymptomatic carotid stenosis (ACS) and cognitive impairment (section 3.10). Since 2017, there is evidence that ACS patients with impaired cerebral vascular reserve (CVR) may be more likely to develop cognitive decline, but there remains no compelling evidence that CEA or CAS improves or prevents cognitive impairment. In the section on timing of CEA after thrombolysis (TT), meta-regression analyses suggest that a delay of six days after lysis completion should be considered before performing CEA, to maintain 30 day death/stroke rates within the 6% recommended threshold (section 4.8). The impetus towards treating symptomatic patients as soon as possible after transient ischaemic attack (TIA) or minor stroke is retained (section 4.5), with CEA being preferred over transfemoral CAS (TFCAS) when interventions are performed in the first 7 – 14 days after symptom onset (section 4.5.4). Whilst transcarotid artery revascularisation (TCAR) has emerged as a promising new CAS technology since 2017, only one registry
      • Cui C.L.
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      has reported outcomes stratified for delays from symptom onset to TCAR (section 4.5.5). The recommendation that patients with 60–99% ACS in the presence of one or more clinical or imaging features that make them higher risk for stroke on best medical therapy, and who should be considered for CEA or CAS has been retained (section 3.6), but 80–99% ACS was not added to the high risk criteria. The rationale underlying this decision is detailed in section 3.6. The section on CAS techniques has been expanded to reflect advances in technology since 2017 (section 6) and there is an updated section on carotid interventions after mechanical thrombectomy (MT) (section 4.9). The guidelines conclude with a list of “unanswered questions”, which highlight areas for future research (section 13), and a new section on Information for the Patient (section 14).

      New recommendations in the 2023 guidelines

      Tabled 1
      New Class I recommendations
      11.For patients with asymptomatic carotid stenosis who are undergoing carotid endarterectomy, lower dose aspirin (75–325 mg daily) rather than higher dose aspirin (> 325 mg daily) is recommended.
      23.For symptomatic carotid stenosis patients who are not being considered for carotid endarterectomy or stenting following a transient ischaemic attack or minor ischaemic stroke, short term aspirin plus clopidogrel for 21 days followed by clopidogrel monotherapy, or long term aspirin plus dipyridamole modified release is recommended.
      24.For recently symptomatic carotid stenosis patients who are not being considered for carotid endarterectomy or stenting who are intolerant of, or allergic to, aspirin and clopidogrel, dipyridamole monotherapy or ticagrelor monotherapy is recommended.
      25.For recently symptomatic carotid stenosis patients in whom carotid endarterectomy is being considered, it is recommended that neurologists/stroke physicians and vascular surgeons develop local protocols to specify preferred antiplatelet regimens (combination therapy vs. monotherapy), so as not to delay urgent carotid surgery.
      29.For symptomatic patients undergoing carotid endarterectomy on aspirin monotherapy, lower dose aspirin (75 – 325 mg daily) rather than higher doses (> 325 mg daily) is recommended.
      30.In symptomatic carotid stenosis patients undergoing carotid endarterectomy who are intolerant of, or allergic to, aspirin and clopidogrel, dipyridamole modified release monotherapy (200 mg twice daily) is recommended.
      35.For symptomatic carotid stenosis patients who do not reach their lipid targets on maximum doses or maximum tolerated doses of statins, ezetimibe (10 mg daily) is recommended.
      58.For patients presenting with recent carotid territory symptoms and evidence of free floating thrombus within the carotid artery, therapeutic anticoagulation is recommended.
      63.For patients with a transient ischaemic attack or minor ischaemic stroke in the presence of newly diagnosed or known atrial fibrillation and an ipsilateral 50–99% carotid stenosis, comprehensive neurovascular work up with multidisciplinary team review is recommended to determine whether urgent carotid revascularisation or anticoagulation alone is indicated.
      64.For patients who have been started on anticoagulation (on the basis that cardiac embolism was considered the most likely cause of their transient ischaemic attack or stroke) but who then report recurrent event(s) in the territory ipsilateral to a 50–99% carotid stenosis whilst on therapeutic levels of anticoagulation, carotid endarterectomy or carotid artery stenting is recommended.
      66.For patients undergoing carotid endarterectomy, it is recommended that the operation be performed by trained vascular surgeons, rather than by surgeons from other specialties.
      91.For patients experiencing a peri-operative stroke, it is recommended to differentiate between an intra-operative and a post-operative stroke.
      92.For patients who develop an ipsilateral neurological deficit after flow is restored following carotid clamp release when carotid endarterectomy is performed under locoregional anaesthesia, immediate re-exploration of the carotid artery is recommended.
      93.For patients who develop an ipsilateral or contralateral stroke at any time period following carotid endarterectomy or carotid artery stenting, urgent diagnostic neurovascular imaging of both carotid arteries and the brain is recommended.
      New Class IIa recommendations
      10.For patients with >50% asymptomatic carotid stenosis who are intolerant or allergic to aspirin, clopidogrel 75 mg daily should be considered. If intolerant or allergic to both aspirin and clopidogrel, dipyridamole monotherapy (200 mg twice daily) should be considered.
      14.For patients with asymptomatic carotid stenosis with dyslipidaemia who are intolerant of statins, with or without ezetimibe, lipid lowering therapy with PCSK9 inhibitors should be considered.
      27.For recently symptomatic patients with a 50–99% carotid stenosis who are to undergo carotid endarterectomy, peri-operative combination antiplatelet therapy should be considered, and should be started after imaging has excluded intracranial haemorrhage.
      28.In recently symptomatic patients with a 50–99% carotid stenosis who are to undergo carotid endarterectomy where antiplatelet monotherapy is preferred to combination therapy, aspirin (300–325 mg daily for 14 days, followed by 75–162 mg daily) should be considered.
      36.For symptomatic carotid stenosis patients who are intolerant of, or not achieving target low density lipoprotein levels on statins, with or without ezetimibe, additional or alternative treatment with PCSK9 inhibitors should be considered
      49.For patients with acute ischaemic stroke due to a symptomatic 50–99% carotid stenosis who have received intravenous thrombolysis, delaying carotid endarterectomy or carotid stenting by six days following completion of thrombolysis should be considered.
      54.For recently symptomatic patients with 50–99% stenoses and contralateral carotid occlusion or previous cervical radiation therapy, the choice of carotid endarterectomy or carotid artery stenting should be considered on an individual basis.
      62.For patients with confirmed ocular ischaemia syndrome and a 50–99% ipsilateral carotid stenosis, carotid endarterectomy or carotid stenting should be considered to prevent further ischaemia induced retinal neovascularisation.
      77.For patients undergoing carotid endarterectomy, intra-operative completion imaging with angiography, duplex ultrasound or angioscopy should be considered in order to reduce the risk of peri-operative stroke.
      79.For patients undergoing carotid endarterectomy, selective wound drainage should be considered.
      82.For patients selected to undergo carotid artery stenting, transradial or transcarotid artery revascularisation should be considered as an alternative to transfemoral carotid artery stenting, especially where transfemoral access may confer a higher risk of complications.
      83.For patients undergoing carotid artery stenting, decisions regarding stent design (open cell, closed cell) should be considered at the discretion of the operator.
      85.For patients undergoing carotid artery stenting, when pre-dilatation is planned, balloon diameters <5 mm should be considered in order to reduce the risk of peri-procedural stroke or transient ischaemic attack.
      88.For patients undergoing carotid artery stenting, decisions regarding choice of cerebral protection (filter, proximal flow reversal) should be considered at the discretion of the operator.
      New Class IIb recommendations
      51.For a patient with acute ischaemic stroke undergoing intracranial mechanical thrombectomy with a tandem 50–99% carotid stenosis and a small area of ipsilateral infarction, synchronous carotid stenting may be considered in the presence of poor antegrade internal carotid artery flow or poor collateralisation via the circle of Willis after mechanical thrombectomy.
      57.For patients with carotid near occlusion and distal vessel collapse with recurrent carotid territory symptoms (despite best medical therapy), carotid endarterectomy or carotid artery stenting may be considered only after multidisciplinary team review.
      59.For patients presenting with recent carotid territory symptoms and free floating thrombus who develop recurrent symptoms whilst receiving anticoagulation therapy, surgical or endovascular removal of the thrombus may be considered.
      61.For symptomatic patients with a carotid web in whom no other cause for stroke can be identified after detailed neurovascular work up, carotid endarterectomy or carotid artery stenting may be considered to prevent recurrent stroke.
      84.For patients undergoing elective carotid artery stenting, dual layer mesh covered stents may be considered.
      90.For patients undergoing transfemoral carotid stenting, at least twelve carotid stent procedures per year (per operator) may be considered an appropriate operator volume threshold to maintain optimal outcomes.
      101.In selected high risk for surgery patients or emergency patients with suspected prosthetic patch infection, insertion of a covered stent may be considered, as part of the three stage EndoVAC technique
      New Class III recommendations
      60.For patients presenting with recent carotid territory symptoms and evidence of free floating thrombus, intravenous thrombolysis is not recommended.
      86.For patients undergoing carotid artery stenting, post-dilation is not recommended when the residual stenosis is <30%, in order to reduce haemodynamic instability.
      128.For patients presenting with a vertebrobasilar territory transient ischaemic attack or stroke and a 50–99% vertebral artery stenosis, routine stenting is not recommended.
      New recommendations included in the European Society for Vascular Surgery 2022 clinical practice guidelines on the management of atherosclerotic carotid and vertebral artery disease in comparison to the previous 2017 guidelines. Numbers correspond to the numbers of the recommendations in the guideline document.

      Unanswered questions from the 2017 guidelines

      In the 2017 guidelines, a series of “unanswered questions” were identified as being priorities for future research.
      • Naylor A.R.
      • Ricco J.B.
      • de Borst G.J.
      • Debus S.
      • de Haro J.
      • Halliday A.
      • et al.
      Management of atherosclerotic carotid and vertebral artery disease: 2017 Clinical practice guidelines of the European Society for Vascular Surgery (ESVS).
      These involved scenarios where there were either no data, or conflicting evidence that did not allow recommendations to be made. The current guidelines have addressed some of the questions (see below). “Unanswered questions” arising from the 2023 guidelines are detailed in section 13.
      Is there a validated algorithm for identifying higher risk of stroke ACS patients?
      The six “higher risk of stroke on BMT” criteria in the 2017 ESVS guidelines have been corroborated by a 2020 meta-analysis of 64 observational studies,
      • Kamtchum-Tatuene J.
      • Noubiap J.J.
      • Wilman A.H.
      • Saqqur A.
      • Jickling G.C.
      Prevalence of high-risk plaques and risk of stroke in patients with asymptomatic carotid stenosis: a meta-analysis.
      with the new data summarised in section 3.6.
      Does ACS cause cognitive decline and can this be reversed or prevented by CEA or CAS?
      A 2021 systematic review identified significant associations between ACS and cognitive impairment (section 3.7), but without clear evidence of a causal relationship, apart from in patients with impaired CVR.
      • Paraskevas K.I.
      • Faggioli G.
      • Ancetti S.
      • Naylor A.R.
      Asymptomatic carotid stenosis and cognitive impairment: a systematic review.
      Impaired CVR is an ESVS criterion for being at higher risk of stroke on BMT in patients in whom CEA (should) or CAS (may) be considered. A second systematic review found no evidence that CEA/CAS significantly improved cognitive function in ACS patients.
      • Ancetti S.
      • Paraskevas K.I.
      • Faggioli G.
      • Naylor A.R.
      Effect of carotid interventions on cognitive function in patients with asymptomatic carotid stenosis: a systematic review.
      Should symptomatic patients start combination antiplatelet therapy once parenchymal haemorrhage is excluded on computed tomography (CT) or magnetic resonance imaging (MRI)?
      Addressed in sections 4.2.2.2 and 4.2.2.4. A meta-analysis of RCTs
      • Hao Q.
      • Tampi M.
      • O’Donnell M.
      • Foroutan F.
      • Siemieniuk R.A.C.
      • Guyatt G.
      Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis.
      showed that early institution of combination APRx significantly reduced non-fatal ischaemic and haemorrhagic stroke, fatal ischaemic stroke, moderate to severe functional disability, and poor quality of life at 90 days vs. aspirin alone in patients with a high risk TIA or minor ischaemic stroke. The 2023 guidelines include a new algorithm detailing various peri-operative combination APRx strategies.
      What is the relevance of new DW-MRI lesions after CEA and CAS, and do they contribute towards higher rates of recurrent stroke or cognitive decline?
      Since 2017, a large study involving patients undergoing non-cardiac surgery reported that post-operative new ischaemic brain lesions (NIBLs) were associated with cognitive impairment, and increased rates of recurrent stroke/TIA.
      NeuroVISION Investigators
      Peri-operative covert stroke in patients undergoing non-cardiac surgery (NeuroVISION): a prospective cohort study.
      The International Carotid Stenting Study (ICSS) also showed that NIBLs were associated with higher rates of recurrent stroke/TIA
      • Gensicke H.
      • van der Worp H.B.
      • Nederkoorn P.J.
      • Macdonald S.
      • Gaines P.A.
      • van der Lugt A.
      • et al.
      Ischemic brain lesions after carotid artery stenting increase future cerebrovascular risk.
      (section 7.1.6).
      Which recently symptomatic patients with < 50% stenoses might benefit from urgent CEA or CAS?
      Addressed in section 4.10. In selected patients experiencing recurrent TIAs or minor ischaemic stroke, despite BMT and who have a < 50% stenosis, CEA or CAS may be considered, but only after multidisciplinary team (MDT) review.
      What is the optimal timing for CEA or CAS after intravenous TT after acute ischaemic stroke?
      Addressed in section 4.8. Meta-regression analyses of non-randomised studies showed that performing CEA early after TT was associated with significantly higher risks, with the absolute risk of stroke/death being reduced to within the current 6% accepted risk threshold after six days had elapsed after TT.
      • Kakkos S.K.
      • Vega de Ceniga M.
      • Naylor A.R.
      A systematic review and meta-analysis of periprocedural outcomes in patients undergoing carotid interventions following thrombolysis.
      There remains debate as to whether CEA should be deferred for six days in all TT patients, or only in those with CT/MRI evidence of acute infarction.
      Which symptomatic patients are at ‘high risk for CEA’ in whom one should preferentially perform CAS?
      Addressed in section 4.11 Vascular registries have proposed several clinical and imaging criteria that were considered to make a patient higher risk for CEA. However, many have now been shown to be incorrect.
      Which symptomatic patients are at ‘high risk for CAS’ in whom one should preferentially perform CEA?
      Addressed in section 7.1.2.1 and includes anatomical variables associated with increases in peri-operative stroke,
      • Fisch U.
      • von Felten S.
      • Wiencierz A.
      • Jansen O.
      • Howard G.
      • Hendrikse J.
      • et al.
      Risk of stroke before revascularisation in patients with symptomatic carotid stenosis: A pooled analysis of randomised controlled trials.
      age > 70,
      • Fisch U.
      • von Felten S.
      • Wiencierz A.
      • Jansen O.
      • Howard G.
      • Hendrikse J.
      • et al.
      Risk of stroke before revascularisation in patients with symptomatic carotid stenosis: A pooled analysis of randomised controlled trials.
      performing transfemoral CAS < 7 days after TIA/stroke,
      • Rantner B.
      • Kollertis B.
      • Roubin G.S.
      • Ringleb P.A.
      • Jansen O.
      • Howard G.
      • et al.
      Early endarterectomy carries a lower procedural risk than early stenting in patients with symptomatic stenosis of the internal carotid artery results from 4 randomized controlled trials.
      long or sequential carotid stenoses,
      • Moore W.S.
      • Popma J.J.
      • Roubin G.S.
      • Voeks J.H.
      • Jones M.
      • Howard G.
      • et al.
      Carotid angiographic characteristics in the CREST trial were major contributors to periprocedural stroke and death differences between carotid artery stenting and carotid endarterectomy.
      heavy calcification,
      • Kokkosis A.A.
      • Macdonald S.
      • Jim J.
      • Shah R.
      • Schneider P.A.
      Assessing the suitability of the carotid bifurcation for stenting: Anatomic and morphologic considerations.
      and a high age related white matter change (ARWMC) score.
      • Ederle J.
      • Davagnanam I.
      • van der Worp H.B.
      • Venables G.S.
      • Lyrer P.A.
      • Featherstone R.L.
      • et al.
      Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial.
      What is the optimal brain protection method during transfemoral CAS: none, distal filter, proximal protection?
      The role of cerebral protection and evidence for varying types of protection systems are addressed in section 6.5. There are no RCT data, but expert consensus remains that some form of protection should be used during CAS.
      Is there a role for stenting in symptomatic patients with extracranial vertebral artery (VA) stenoses?
      Addressed in section 12.6.2.1, which includes a 2019 meta-analysis of three RCTs.
      • Markus H.S.
      • Harshfield E.L.
      • Compter A.
      • Kuker W.
      • Kappelle L.J.
      • Clifton A.
      • et al.
      Stenting for symptomatic vertebral artery stenosis: a preplanned pooled individual patient data analysis.
      Recommendations remain unchanged; VA stenting should be considered only in patients with recurrent symptoms despite BMT.
      What is the optimal way to treat a recently symptomatic patient with an intracranial VA stenosis?
      Addressed in section 12.6.2.1, which includes a 2019 meta-analysis of three RCTs.
      • Markus H.S.
      • Harshfield E.L.
      • Compter A.
      • Kuker W.
      • Kappelle L.J.
      • Clifton A.
      • et al.
      Stenting for symptomatic vertebral artery stenosis: a preplanned pooled individual patient data analysis.
      The 2023 guidelines recommend BMT, rather than stenting.
      Should symptomatic patients with vertebrobasilar TIA/stroke be started on combination APRx once parenchymal haemorrhage is excluded on CT/MRI?
      No RCTs have addressed this question in patients with vertebrobasilar (VB) symptoms. However, a meta-analysis of three RCTs
      • Hao Q.
      • Tampi M.
      • O’Donnell M.
      • Foroutan F.
      • Siemieniuk R.A.C.
      • Guyatt G.
      Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis.
      in patients with minor ischaemic stroke or TIA (which included VB patients) showed that early institution of combination APRx significantly reduced non-fatal ischaemic and haemorrhagic stroke, fatal ischaemic stroke, moderate to severe functional disability and poor quality of life at 90 days vs. aspirin alone (section 4.2.2.2). Recommendations regarding APRx in VB patients are the same as for carotid territory stroke/TIA.
      What is the optimal method for detecting VA re-stenoses after stenting?
      Duplex ultrasound (DUS) may be performed after stenting of ostial or proximal VA lesions (section 12.7). Suspected re-stenoses should be corroborated by CT angiography (CTA) or MR angiography (MRA). Distal VA interventions require surveillance with CTA/MRA.
      How should > 70% asymptomatic re-stenoses after VA stenting be managed?
      Only one registry (n = 72) has addressed this question
      • Qiu Z.
      • Liu J.
      • Huang R.
      • Liu D.
      • Dai Z.
      • Luo M.
      • et al.
      Incidence, risk, and treatment of binary restenosis after vertebral artery stenting.
      (section 12.6.5.2). Re-intervention did not significantly reduce stroke/TIA at one year (vs. BMT patients), but 33% of treated patients developed recurrent re-stenoses. Recurrent re-stenoses were significantly more likely to occur after balloon angioplasty than redo stenting.

      1. Methodology

      1.1 Purpose of the guidelines

      ESVS has prepared guidelines for treating patients with atherosclerotic carotid and VA disease, in succession to the 2009 and 2017 versions.
      • Naylor A.R.
      • Ricco J.B.
      • de Borst G.J.
      • Debus S.
      • de Haro J.
      • Halliday A.
      • et al.
      Management of atherosclerotic carotid and vertebral artery disease: 2017 Clinical practice guidelines of the European Society for Vascular Surgery (ESVS).
      ,
      • Liapis C.D.
      • Bell P.R.F.
      • Mikhailidis D.
      • Sivenius J.
      • Nicolaides A.
      • Fernandes e Fernandes J.
      • et al.
      on behalf of the ESVS Guidelines Collaborators. ESVS Guidelines. Invasive treatment for carotid stenosis: Indications and techniques.
      Non-atherosclerotic pathologies (arteritis, fibromuscular dysplasia, dissection, aneurysm) are not included as they will be the subject of a separate guideline. Potential users include vascular surgeons, neurologists, angiologists, stroke physicians, primary care doctors, cardiologists, and interventional radiologists. A key aim is to optimise “shared decision making”, where the patient has choice and control over how they prefer to be treated and how their care is delivered. This requires the doctor to provide as much evidence based information as possible regarding all available treatment options (i.e., not just those preferred by the treating doctor), together with a balanced discussion of risks, benefits, and potential consequences in a manner the patient understands, and which takes account of his/her preferences. Guidelines promote standards of care but are not a legal standard of care. They are a “guiding principle” and care delivered depends on patient presentation, choice, comorbidities, and setting (techniques available, local expertise). The 2023 guidelines are published in the European Journal of Vascular and Endovascular Surgery (EJVES), as an online open access publication, as well as being free to access via the ESVS website. They will also be available on a dedicated ESVS App.

      1.2 Compliance with AGREE II standards

      AGREE II reporting standards for assessing the quality and reporting of practice guidelines were adopted during preparation of the 2023 guidelines

      AGREE II. Available at: agreetrust.org/agree-ii/ [Accessed 25 January 2022].

      and a checklist is available (Appendix A). There was no formal evaluation of Facilitators and Barriers and the guidelines did not have the scope to go into detail regarding health economics, largely because individual countries have different processes for determining cost acceptability.

      1.3 Guideline Writing Committee

      Guideline Writing Committee (GWC) members were selected by the GWC chairs and ESVS Guidelines Committee (GC) chair to represent clinicians involved in decision making in patients with atherosclerotic carotid and VA disease. The GWC comprised vascular surgeons, stroke physicians/neurologists, interventional radiologists, and interventional cardiologists (see Appendix B for specialty and institution). Views and preferences for the target population were not sought directly, but Mr Chris Macey of the Irish Heart Foundation and the Stroke Alliance for Europe collaborated in preparing section 14 (Information for Patients). GWC members provided disclosure statements regarding relationships that could be perceived as conflicts of interest (these are filed and available at ESVS headquarters via [email protected] ). GWC members received no financial support from any pharmaceutical, device, or industry body, to develop the guidelines.

      1.4 Evidence collection

      A video conference was held on 6 July 2020, at which topics and tasks were allocated. The GWC met monthly (by video conference) to review progress. Search strategies were undertaken for each of the 46 subsections, using Medline, Embase, and the Cardiosource Clinical Trials and Cochrane databases to 31 December 2020, plus reference checking of cited papers. Hand searches were undertaken of publications in 11 journals between 2017 and 2020 including: EJVES, the Journal of Vascular Surgery, Annals of Vascular Surgery, Stroke, The Journal of Stroke and Cerebrovascular Disease, Neurology, Lancet Neurology, Cerebrovascular Diseases, the International Journal of Stroke, Stroke and Vascular Neurology, and the European Stroke Journal. At the request of the GC, selected articles published between January and December 2021 were included if they added important information that influenced decision making and recommendations. Only peer reviewed publications were included, following the Pyramid of Evidence principle (Table 1, Table 2). Multiple RCTs or meta-analyses of multiple RCTs were at the top, then single RCTs or large non-randomised studies (including meta-analyses of large non-RCTs), meta-analyses of small non-RCTs, observational studies, case series, and large prospective audits. Expert opinion was at the bottom of the pyramid, while case reports and abstracts were excluded. The evidence used in each of the 38 new recommendations is detailed in the Tables of Evidence (Appendix C).
      Table 1Classes of recommendations according to the ESC (European Society of Cardiology)
      Class of recommendationDefinitionSuggested wording
      Class IEvidence and/or general agreement that a given treatment or procedure is beneficial, useful and effectiveIs recommended
      Class IIConflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure
      Class IIaWeight of evidence/opinion is in favour of usefulness/efficacyShould be considered
      Class IIbUsefulness/efficacy is less well established by evidence/opinionMay be considered
      Class IIIEvidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmfulIs not recommended, should not be done
      Table 2Levels of evidence according to the ESC (European Society of Cardiology)
      Level of evidence AData derived from multiple randomised clinical trials or meta-analyses of randomised trials
      Level of evidence BData derived from a single randomised clinical trial or large non-randomised studies
      Level of evidence CConsensus of opinion of experts and/or small studies, retrospective studies, registries

      1.5 Studies commissioned for the guidelines

      Four systematic reviews/meta-analyses were commissioned: (i) the association between ACS and cognitive impairment;
      • Paraskevas K.I.
      • Faggioli G.
      • Ancetti S.
      • Naylor A.R.
      Asymptomatic carotid stenosis and cognitive impairment: a systematic review.
      (ii) the effect of carotid interventions on cognitive function in ACS patients;
      • Ancetti S.
      • Paraskevas K.I.
      • Faggioli G.
      • Naylor A.R.
      Effect of carotid interventions on cognitive function in patients with asymptomatic carotid stenosis: a systematic review.
      (iii) the effect of timing of carotid interventions on outcomes in the early time period after symptom onset;
      • Coelho A.
      • Peixoto J.
      • Mansilha A.
      • Naylor A.R.
      • de Borst G.J.
      Timing of carotid intervention in symptomatic carotid stenosis: A systematic review and meta-analysis.
      and (iv) the effect of timing of carotid interventions on outcomes in patients with acute ischaemic stroke undergoing TT.
      • Kakkos S.K.
      • Vega de Ceniga M.
      • Naylor A.R.
      A systematic review and meta-analysis of periprocedural outcomes in patients undergoing carotid interventions following thrombolysis.

      1.6 Recommendations

      The European Society of Cardiology (ESC) system was used to develop classes of recommendation and levels of evidence. The strength (class) is graded from I to III, with I being the strongest (Table 1). The letters A, B, C denote evidence levels (Table 2), with A being the highest.
      Recommendations were developed by GWC members assigned to each section and all GWC members then reviewed each completed section and approved the final wording and grading of the recommendation. During preparation of the first (and subsequent) drafts, GWC members participated in video conferences where the wording and grading of all recommendations were checked before being submitted for external review. If there was not unanimous agreement to begin with, regarding the grading/wording of recommendations, discussions were held to decide how this might be achieved. Ultimately, the wording and grading of all published recommendations secured unanimous agreement among the GWC, although a majority vote (11:3) was taken on the decision not to include 80–99% ACS as a “high risk of stroke on medical therapy” criterion in ACS patients (section 3.6).
      Since 2017, the GC undertook a review of the criteria for grading the class and level of evidence, to ensure these were standardised for future ESVS guidelines, especially regarding subgroup analyses from RCTs. A modified ESC system was used to classify the level of evidence and to determine the strength of recommendation. In this modified system, RCT meta-analyses are level A; larger non-RCT meta-analyses are level B; while meta-analyses of small non-randomised studies are level C. Furthermore, predefined subgroup analyses of RCTs or large RCT subgroup analyses can be level A, while other subgroup analyses of RCTs should be considered level B. As a consequence, while the wording of 11 recommendations remains essentially unchanged (compared with 2017), grades of evidence have been revised and the relevant recommendation box is highlighted as having been “changed”.

      1.7 Review process

      There were three rounds of external review, involving 25 reviewers (16 GC members plus nine external reviewers). Review comments were assessed by the co-chairs, who coordinated a response to each comment via a formal revision process and GWC video conferences. The final version was approved by GWC members before submission to EJVES Editors on 6 April 2022.

      1.8 Audit and update plan

      These guidelines will be updated every four years. Vascular centres are encouraged to audit implementations made as a result of the guidelines. Audit cycles should be repeated and changes implemented. There are many ways to perform clinical audit and it is now a requirement for most centres to be registered with local audit committees.

      2. Introduction

      Primary prevention aims to reduce the clinical impact of ACS and VA stenoses (to prevent TIA or stroke). The goal of secondary prevention is to prevent recurrent TIA, stroke or vascular events in patients presenting with TIA or ischaemic stroke, secondary to carotid or VA stenoses.

      2.1 Definition of stroke and transient ischaemic attack

      The term “cerebrovascular accident” has been replaced with TIA or stroke. Because many studies in carotid stenosis patients pre-dated debates about whether to classify TIA/stroke as time based or tissue based,
      • Sacco R.L.
      • Kasner S.E.
      • Broderick J.P.
      • Caplan L.R.
      • Connors J.J.
      • Culebras A.
      • et al.
      Updated definition of stroke for the 21st century. A statement for healthcare professionals from the American Heart Association/American Stroke Association.
      this guideline has retained time based definitions. TIA is an episode of focal brain, retinal, or spinal cord dysfunction lasting < 24 hours, which is of a non-traumatic, vascular origin.
      • Bamford J.
      Clinical examination in diagnosis and subclassification of stroke.
      Crescendo TIAs refer to multiple TIAs in a short time period, defined by some as more than two TIAs in 24 hours,
      • Dorigo W.
      • Pulli R.
      • Nesi M.
      • Alessi Innocenti A.
      • Pratesi G.
      • Inzitari D.
      • Pratesi C.
      Urgent carotid endarterectomy in patients with recent/crescendo transient ischaemic attacks or acute stroke.
      or at least three events in seven days,
      • Karkos C.D.
      • McMahon G.
      • McCarthy M.J.
      • Dennis M.J.
      • Sayers R.D.
      • London N.J.
      • et al.
      The value of urgent carotid surgery for crescendo transient ischemic attacks.
      with full recovery between. Stroke is a sudden onset focal (rather than global) neurological dysfunction, with symptoms lasting > 24 hours (or causing death in < 24 hours), which is of non-traumatic, vascular origin.
      • Bamford J.
      Clinical examination in diagnosis and subclassification of stroke.
      Stroke in evolution refers to a fluctuating neurological deficit (without full recovery), or a progressively worsening neurological deficit over 24 hours.
      • Dorigo W.
      • Pulli R.
      • Nesi M.
      • Alessi Innocenti A.
      • Pratesi G.
      • Inzitari D.
      • Pratesi C.
      Urgent carotid endarterectomy in patients with recent/crescendo transient ischaemic attacks or acute stroke.

      2.2 Burden of stroke

      In a European population of 715 million, 1.4 million strokes occur annually.
      GBD16 Stroke Collaborators
      Global, regional and national burdens of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study of 2016.
      Stroke accounts for 1.1 million deaths annually in Europe and is the second commonest cause of death after coronary artery disease (CAD).
      GBD16 Stroke Collaborators
      Global, regional and national burdens of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study of 2016.
      It is suggested that the number of Europeans living with stroke as a chronic condition may increase by 25% from 3.7 million (2015) to 4.6 million (2035), as a result of the ageing population.

      Stroke Alliance for Europe: The burden of stroke in Europe. Available at: www.strokeeurope.eu [Accessed 4 February 2020].

      Including indirect costs, European health systems spent € 45 billion annually on stroke care in 2015.

      Stroke Alliance for Europe: The burden of stroke in Europe. Available at: www.strokeeurope.eu [Accessed 4 February 2020].

      In the United States of America, total stroke costs were $ 49.5 billion (€ 43.9 billion) in 2015 – 2016,

      AHRQ Data Tools. Available at: https://datatools.ahrq.gov [Accessed 25 January 2022].

      and are expected to increase to $ 129 billion (€ 114 billion) by 2035.
      RTI International
      Projections of Cardiovascular Disease Prevalence and Costs: 2015–2035: Technical Report [report prepared for the American Heart Association.

      2.3 Aetiology of stroke

      Of strokes, 15–20% are haemorrhagic (intracranial [ICH], subarachnoid), while 20% of ischaemic strokes are vertebrobasilar (VB). The Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification for TIA/ischaemic stroke includes five categories: (1) large artery atherosclerosis (LAA): defined as ≥ 50% stenosis or occlusion of an extra- or intracranial artery); (2) cardioembolic; (3) small vessel occlusion; (4) other aetiologies (arteritis, dissection); and (5) undetermined aetiology (two potential causes, no cause identified, incomplete investigations).
      • Adams H.P.
      • Bendixen B.H.
      • Kappelle L.J.
      • Biller J.
      • Love B.B.
      • Gordon D.L.
      • et al.
      Classification of subtype of acute ischaemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke therapy.
      In 2 204 ischaemic stroke patients, LAA was responsible for 16.6% of strokes. An ipsilateral 50–99% carotid stenosis was identified in 8%, while carotid occlusion or intracranial disease accounted for 3.5% each.
      • Flaherty M.L.
      • Kissela B.
      • Khoury J.C.
      • Alwell K.
      • Mooman C.J.
      • Woo D.
      • et al.
      Carotid artery stenosis as a cause of stroke.
      In another prospective study (883 patients with carotid territory symptoms), 4% had 50–69% ipsilateral carotid stenoses, while 8% had 70–99% stenosis. Overall, 12.5% had an ipsilateral 50–99% stenosis, while another 5.2% had ipsilateral occlusion.
      • den Brok M.G.H.E.
      • Kuhrij L.S.
      • Roozenbeek R.
      • van der Ligt A.
      • Hilkens P.H.E.
      • Dippel D.W.J.
      • et al.
      Prevalence and risk factors of symptomatic carotid stenosis in patients with recent TIA or ischaemic stroke in the Netherlands.
      The proportion of LAA strokes may be declining, in association with proportional increases in cardioembolic stroke,
      • Rosales J.S.
      • Alet M.J.
      • Pujol Lereis V.A.
      • Ameriso S.F.
      Fall in the proportion of atherothrombotic strokes during the last decade.
      attributed to declines in total cholesterol, low density lipoprotein cholesterol (LDL-C), blood pressure (BP), increases in high density lipoprotein cholesterol,
      • Hackam D.G.
      • Spence J.D.
      Decline in the severity of carotid atherosclerosis and associated risk factors from 2002–2014.
      and substantial increases in APRx, antihypertensive, and statin prescriptions.
      • Rosales J.S.
      • Alet M.J.
      • Pujol Lereis V.A.
      • Ameriso S.F.
      Fall in the proportion of atherothrombotic strokes during the last decade.
      Between 2002 and 2014, there was a 30% decline in the prevalence of 60–99% carotid stenoses and a 36% decline in 80–99% stenoses in patients referred to a TIA/stroke service.
      • Hackam D.G.
      • Spence J.D.
      Decline in the severity of carotid atherosclerosis and associated risk factors from 2002–2014.

      2.4 Methods for measuring carotid artery stenosis severity

      The European Carotid Surgery Trial (ECST)
      European Carotid Surgery Trialists’ Collaborative Group
      MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70–99%) or with mild (0–29%) carotid stenosis. European Carotid Surgery Trialists' Collaborative Group.
      and the North American Symptomatic Carotid Endarterectomy Trial (NASCET)
      North American Symptomatic Carotid Endarterectomy Trial Collaborators
      Beneficial effect of carotid endarterectomy in symptomatic patients with high grade carotid stenosis.
      adopted different methods for measuring stenosis (Figure 1).
      Figure 1
      Figure 1North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) methods for measuring carotid stenosis severity.
      Both methods used residual lumen diameter as the numerator. In ECST, the denominator was the estimated vessel diameter where the residual lumen was measured (usually the carotid bulb). In NASCET, the denominator was the diameter of disease free internal carotid artery (ICA) above the stenosis, where vessel walls were parallel. A 50% NASCET stenosis equates to a 75% ECST, while a 70% NASCET stenosis equates to an 85% ECST (Figure 1).
      • Donnan G.A.
      • Davis S.M.
      • Chambers B.R.
      • Gates P.C.
      Surgery for prevention of stroke.
      Uncertainty about methods used can lead to inappropriate patient selection (exclusion) for interventions.
      • Walker J.
      • Naylor A.R.
      Ultrasound based diagnosis of ‘carotid stenosis >70%’: an audit of UK practice.
      The NASCET method has been adopted in the current guidelines, unless stated otherwise. The NASCET method does not permit measurement of stenosis severity in large volume plaques in dilated carotid bulbs. Here, the lumen may be slightly less than that of the distal ICA, so NASCET records a < 50% stenosis, while ECST measures > 70%. Symptomatic patients with large volume plaques consistent with an ECST > 70% stenosis should, therefore, be considered for revascularisation.
      The NASCET method has limitations regarding chronic near occlusion (CNO) with distal vessel collapse (section 4.12) unless the contralateral ICA is used as the denominator. In the RCTs, angiographic criteria for differentiating between CNO and a severe stenosis without distal collapse included at least two of (i) delayed contrast filling above ipsilateral stenosis; (ii) recruitment of circle of Willis (CoW) or distal ICA collaterals; (iii) diameter of distal ipsilateral ICA less than contralateral ICA; and (iv) distal ICA diameter equal to or less than diameter of the ipsilateral external carotid artery (ECA).
      • Fox A.J.
      • Eliasziw M.
      • Rothwell P.M.
      • Schmidt M.H.
      • Warlow C.P.
      • Barnett H.J.
      Identification, prognosis and management of patients with carotid artery near occlusion.
      CNO with complete vessel collapse and a “threadlike” distal lumen (previously known as string sign, slim sign, or subocclusion) and CNO with partial vessel collapse have a prevalence < 10% in patients with significant carotid disease.
      • Johansson E.
      • Fox A.J.
      Carotid near-occlusion: a comprehensive review: Part 1 – definition, terminology, and diagnosis.
      Because angiograms are not routinely performed, CTA criteria have been developed to differentiate CNO from a 90– 95% stenosis with no distal vessel collapse, including (i) residual lumen ≤ 1.3 mm; (ii) ipsilateral distal ICA diameter ≤ 3.5 mm; (iii) ratio of ipsilateral distal ICA diameter to contralateral ICA ≤ 0.87; and (iv) ratio of ipsilateral distal ICA diameter to ipsilateral ECA diameter ≤ 1.27.
      • Bartlett E.S.
      • Walters T.D.
      • Symons S.P.
      • Fox A.J.
      Diagnosing carotid stenosis near occlusion by using CT angiography.
      . It has also been proposed that the combination of distal ICA diameter ≤ 2 mm and an ICA diameter ratio ≤ 0.42 offers better prognostic discrimination.
      • Johansson E.
      • Gu T.
      • Fox A.J.
      Defining carotid near-occlusion with full collapse: a pooled analysis.

      2.5 Imaging strategies in carotid artery disease

      Tabled 1
      Recommendation 1Changed
      For patients undergoing evaluation of the extent and severity of extracranial carotid stenoses, duplex ultrasound, computed tomographic angiography and/or magnetic resonance angiography are recommended.
      ClassLevelReferencesToE
      IBWardlaw et al. (2006)
      • Wardlaw J.M.
      • Chappell F.M.
      • Stevenson M.
      • De Nigris E.
      • Thomas S.
      • Gillard J.
      • et al.
      Accurate, practical and cost-effective assessment of carotid stenosis in the UK.
      ,

      Patel et al. (2002)
      • Patel S.G.
      • Collie D.A.
      • Wardlaw J.M.
      • Lewis S.C.
      • Wright A.R.
      • Gibson R.J.
      • et al.
      Outcome, observer reliability, and patient preferences if CTA, MRA, or Doppler ultrasound were used, individually or together, instead of digital subtraction angiography before carotid endarterectomy.
      Tabled 1
      Recommendation 2Changed
      For patients where carotid endarterectomy is being considered, it is recommended that duplex ultrasound stenosis estimation be corroborated by computed tomographic angiography or magnetic resonance angiography, or by a repeat duplex ultrasound performed by a second operator.
      ClassLevelReferencesToE
      IBWardlaw et al. (2006)
      • Wardlaw J.M.
      • Chappell F.M.
      • Stevenson M.
      • De Nigris E.
      • Thomas S.
      • Gillard J.
      • et al.
      Accurate, practical and cost-effective assessment of carotid stenosis in the UK.
      Tabled 1
      Recommendation 3Changed
      For a patient where carotid artery stenting is being considered, it is recommended that any duplex ultrasound study be followed by computed tomographic angiography or magnetic resonance angiography, which will provide additional information on the aortic arch, as well as the extra- and intracranial circulation.
      ClassLevelReferencesToE
      IBWardlaw et al. (2006)
      • Wardlaw J.M.
      • Chappell F.M.
      • Stevenson M.
      • De Nigris E.
      • Thomas S.
      • Gillard J.
      • et al.
      Accurate, practical and cost-effective assessment of carotid stenosis in the UK.
      Tabled 1
      Recommendation 4Unchanged
      In units which base management decisions in patients with atherosclerotic carotid disease on duplex ultrasound measurement, it is recommended that reports should state which measurement method is used.
      ClassLevelReferencesToE
      ICWalker et al. (2006)
      • Walker J.
      • Naylor A.R.
      Ultrasound based diagnosis of ‘carotid stenosis >70%’: an audit of UK practice.
      Tabled 1
      Recommendation 5Changed
      For patients with atherosclerotic disease being considered for revascularisation, intra-arterial digital subtraction angiography is not recommended, unless there are significant discrepancies on non-invasive imaging.
      ClassLevelReferencesToE
      IIIBWardlaw et al. (2006)
      • Wardlaw J.M.
      • Chappell F.M.
      • Stevenson M.
      • De Nigris E.
      • Thomas S.
      • Gillard J.
      • et al.
      Accurate, practical and cost-effective assessment of carotid stenosis in the UK.
      Table 3Sensitivity and specificity of duplex ultrasound (DUS), computed tomographic angiography (CTA), and contrast enhanced magnetic resonance angiography (CEMRA), compared with digital subtraction angiography (DSA)
      Data derived from Rojoa91 and Wardlaw.199
      in imaging of carotid artery disease
      DUSCTACEMRA
      Sensitivity – %Occlusion979799
      Stenosis8975–8594–95
      Specificity – %Occlusion999999
      Stenosis8493–9692–93
      Data derived from Rojoa
      • Rojoa D.M.
      • Lodhi A.Q.D.
      • Kontopodis N.
      • Ioannou C.V.
      • Labropoulos N.
      • Antoniou G.A.
      Ultrasonography for the diagnosis of extracranial carotid occlusion: diagnostic test accuracy meta-analysis.
      and Wardlaw.
      • Wardlaw J.M.
      • Chappell F.M.
      • Stevenson M.
      • De Nigris E.
      • Thomas S.
      • Gillard J.
      • et al.
      Accurate, practical and cost-effective assessment of carotid stenosis in the UK.

      2.6 Role of the multidisciplinary team

      Tabled 1
      Recommendation 6Unchanged
      Multidisciplinary team review is recommended to reach consensus decisions regarding the indications for, and treatment of, patients with carotid stenosis regarding carotid endarterectomy, carotid stenting or optimal medical therapy.
      ClassLevelReferencesToE
      ICBazan et al. (2014)
      • Bazan H.A.
      • Caton G.
      • Talebinejad S.
      • Hoffman R.
      • Smith T.A.
      • Vidal G.
      • et al.
      A stroke/vascular neurology service increases the volume of urgent carotid endarterectomies performed in a tertiary referral center.
      Tabled 1
      Recommendation 7Unchanged
      Independent neurological assessment before and after carotid interventions is recommended to audit peri-procedural risks.
      ClassLevelReferencesToE
      ICRothwell et al. (1995)
      • Rothwell P.M.R.
      • Warlow C.P.
      Is self-audit reliable?.
      ,

      Theiss et al. (2004)
      • Theiss W.
      • Hermanek P.
      • Mathias K.
      • Ahmadi R.
      • Heuser L.
      • Hoffmann F.J.
      • et al.
      Pro-CAS: a prospective registry of carotid angioplasty and stenting.

      3. Management of asymptomatic carotid disease

      An asymptomatic carotid artery stenosis (ACS) refers to a stenosis detected in patients without any clinical history of ischaemic stroke, TIA, or other neurological symptoms which might be referable to the carotid arteries. These were the inclusion criteria adopted by ACAS,
      Executive Committee for the Asymptomatic Carotid Atherosclerosis Study
      Endarterectomy for asymptomatic carotid artery stenosis.
      while patients randomised within ACST-1 should not have reported any symptoms referable to the ipsilateral ACS within the preceding six months.
      MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group
      Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.

      3.1 Optimal medical therapy

      Most primary prevention RCTs did not specifically recruit ACS patients, focussing primarily on stroke prevention in general. Some did include ACS patients or published subgroup analyses in ACS patients, and these have been highlighted where appropriate.

      3.1.1 Lifestyle measures

      Tabled 1
      Recommendation 8Changed
      For patients with asymptomatic and symptomatic carotid disease, behavioural counselling to promote healthy diet, smoking cessation and physical activity is recommended.
      ClassLevelReferencesToE
      IBO'Connor et al. (2020)
      • O’Connor E.A.
      • Evans C.V.
      • Rushkin M.C.
      • Redmons N.
      • Lin J.S.
      Behavioural counselling to promote a healthy diet and physical activity for cardiovascular disease prevention in adults with cardiovascular risk factors: updated evidence report and systematic review for the US Preventive Services Task Force.
      ,

      Herder et al. (2012)
      • Herder M.
      • Johnsen S.H.
      • Arntzen K.A.
      • Mathiesen E.B.
      Risk factors for progression of carotid intima-media thickness and total plaque area: a 13-year follow-up study: the Tromso Study.
      ,

      Shinton et al. (1989)
      • Shinton R.
      • Beevers G.
      Meta-analysis of relation between cigarette smoking and stroke.
      ,

      Lee et al. (2003)
      • Lee C.D.
      • Folsom A.R.
      • Blair S.N.
      Physical activity and stroke risk: a meta-analysis.
      ,

      Strazzullo et al. (2010)
      • Strazzullo P.
      • D’Elia L.
      • Cairella G.
      • Garbagnati F.
      • Cappuccio F.P.
      • Scalfi L.
      Excess body weight and incidence of stroke: meta-analysis of prospective studies with 2 million participants.

      3.1.2 Antiplatelet therapy

      3.1.2.1 Monotherapy

      Only one RCT (which did not show benefit) and one observational study (which did show benefit) evaluated APRx in patients with > 50% ACS on BMT (Table 4).
      Table 4Studies evaluating antiplatelet therapy in asymptomatic carotid stenosis patients
      Study nameStenosis severityStudy methodFollow up timePrinciple findings
      Asymptomatic Cervical Bruit Study
      • Cote R.
      • Battista R.N.
      • Abrahamowicz M.
      • Langlois Y.
      • Bourque F.
      • Mackey A.
      Lack of effect of aspirin in asymptomatic patients with carotid bruits and substantial carotid narrowing. The Asymptomatic Cervical Bruit Study Group.
      50–100%RCT: 325 mg enteric coated aspirin daily (n = 188) vs. placebo (n = 188)Median 2.3 yNo difference in composite endpoint of TIA, ischaemic stroke, unstable angina, MI and any cause death between groups (HR 0.99, 95% CI 0.67–1.46; p = .61)
      Asymptomatic Carotid Emboli Study
      • King A.
      • Shipley M.
      • Markus H.
      The effect of medical treatments on stroke risk in asymptomatic carotid stenosis.
      70–99%Observational: APRx (n = 419) vs. no APRx (n = 58) at baselineMean 2 yAPRx significantly reduced risk of ipsilateral stroke or TIA (HR 0.45, 95% CI 0.31–0.66) and any stroke or cardiovascular death (HR 0.13, 95% CI 0.06–0.27) vs. no APRx
      RCT = randomised controlled trial; APRx = antiplatelet therapy; TIA = transient ischaemic attack; MI = myocardial infarction; HR = hazard ratio; CI = confidence interval.
      Two thirds of ACS patients have subclinical CAD.
      • Adams R.J.
      • Chimowitz M.I.
      • Alpert J.S.
      • Awad I.A.
      • Cerqueria M.D.
      • Fayad P.
      • et al.
      Coronary risk evaluation in patients with transient ischemic attack and ischemic stroke: a scientific statement for healthcare professionals from the Stroke Council and the Council on Clinical Cardiology of the American Heart Association/American Stroke Association.
      In a systematic review of 17 observational studies in 11 391 patients with > 50% ACS, 63% of deaths were cardiac (average annual cardiac mortality 2.9%).
      • Giannopoulos A.
      • Kakkos S.
      • Abbott A.
      • Naylor A.R.
      • Richards T.
      • Mikhailidis D.P.
      • et al.
      Long-term mortality in patients with asymptomatic carotid stenosis: implications for statin therapy.
      A meta-analysis of primary prevention trials reported that aspirin conferred a 12% reduction in serious vascular events, mainly through reduced non-fatal myocardial infarction (MI), 0.18% vs. 0.23% per year (HR 0.77; 95% CI 0.67 – 0.89, p < .001).
      • Baigent C.
      • Blackwell L.
      • Collins R.
      • Emberson J.
      • Godwin J.
      • et al.
      Antithrombotic Trialists Collaboration
      Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.
      There are no large scale RCT data on the efficacy of clopidogrel, dipyridamole, ticagrelor, or prasugrel in ACS patients. If intolerant of aspirin, clopidogrel is a reasonable alternative, based on data extrapolation from ischaemic stroke patients.
      • Murphy S.J.X.
      • Naylor A.R.
      • Ricco J.B.
      • Sillesen H.
      • Kakkos S.
      • Halliday A.
      • et al.
      Optimal antiplatelet therapy in moderate to severe asymptomatic and symptomatic carotid stenosis: a comprehensive review of the literature.
      ,
      CAPRIE Steering Committee
      A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee.
      If intolerant of, or allergic to, aspirin and clopidogrel, 200 mg dipyridamole twice daily is an alternative,
      • Murphy S.J.X.
      • Naylor A.R.
      • Ricco J.B.
      • Sillesen H.
      • Kakkos S.
      • Halliday A.
      • et al.
      Optimal antiplatelet therapy in moderate to severe asymptomatic and symptomatic carotid stenosis: a comprehensive review of the literature.
      also based on data extrapolation from TIA/stroke patients.
      • Diener H.C.
      • Cunha L.
      • Forbes C.
      • Sivenius J.
      • Smets P.
      • Lowenthal A.
      European Stroke Prevention Study. 2. Dipyridamole and acetylsalicyclic acid in the prevention of stroke.

      3.1.2.2 Combination

      No RCT data support long term aspirin + clopidogrel or aspirin + dipyridamole in ACS patients, unless for other clinical indications.

      3.1.2.3 In patients undergoing carotid endarterectomy

      In the Aspirin and Carotid Endarterectomy Trial (ACE), 2 849 ACS/SCS patients undergoing CEA were randomised to four doses of aspirin (81 mg, 325 mg, 650 mg, 1 300 mg). In an efficacy analysis, which excluded patients on ≥ 650 mg aspirin before randomisation, the composite risk of 30 day stroke/MI/death was statistically significantly lower in patients randomised to 81 – 325 mg aspirin (3.7%) vs. 650 – 1 300 mg (8.2%; p < .001).
      • Taylor D.W.
      • Barnett H.J.
      • Haynes R.B.
      • Ferguson G.G.
      • Sackett D.L.
      • Thorpe K.E.
      • et al.
      Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy: a randomised controlled trial. ASA and Carotid Endarterectomy (ACE) Trial Collaborators.
      No RCTs have evaluated clopidogrel monotherapy or combination APRx in ACS patients undergoing CEA. If aspirin intolerant, it is reasonable to prescribe clopidogrel.
      • Murphy S.J.X.
      • Naylor A.R.
      • Ricco J.B.
      • Sillesen H.
      • Kakkos S.
      • Halliday A.
      • et al.
      Optimal antiplatelet therapy in moderate to severe asymptomatic and symptomatic carotid stenosis: a comprehensive review of the literature.
      If intolerant or allergic to aspirin and clopidogrel, 200 mg dipyridamole monotherapy is an alternative.
      • Murphy S.J.X.
      • Naylor A.R.
      • Ricco J.B.
      • Sillesen H.
      • Kakkos S.
      • Halliday A.
      • et al.
      Optimal antiplatelet therapy in moderate to severe asymptomatic and symptomatic carotid stenosis: a comprehensive review of the literature.

      3.1.2.4 In patients undergoing carotid artery stenting

      Table 5 summarises two RCTs evaluating APRx (and i.v. heparin) in patients undergoing CAS. In RCTs comparing CEA with CAS in ACS patients, aspirin + clopidogrel was recommended for > 24 hours
      • Mannheim D.
      • Karmeli R.
      Prospective randomized trial comparing endarterectomy to stenting in severe asymptomatic carotid stenosis.
      ,
      • Gurm H.S.
      • Yadav J.S.
      • Fayad P.
      • Katzen B.T.
      • Mishkel G.J.
      • Bajwa T.K.
      • et al.
      Long-term results of carotid stenting versus endarterectomy in high-risk patients.
      to three days pre-operatively,
      • Rosenfield K.
      • Matsumura J.S.
      • Chaturvedi S.
      • Riles T.
      • Ansel G.M.
      • Metzger D.C.
      • et al.
      Randomized trial of stent versus surgery for asymptomatic carotid stenosis.
      ,
      • Eckstein H.H.
      • Reiff T.
      • Ringleb P.
      • Jansen O.
      • Mansmann U.
      Hacke W for the SPACE 2 Investigators. SPACE-2: a missed opportunity to compare carotid endarterectomy, carotid stenting, and best medical treatment in patients with asymptomatic carotid stenoses.
      and for two to four weeks
      • Gurm H.S.
      • Yadav J.S.
      • Fayad P.
      • Katzen B.T.
      • Mishkel G.J.
      • Bajwa T.K.
      • et al.
      Long-term results of carotid stenting versus endarterectomy in high-risk patients.
      ,
      • Rosenfield K.
      • Matsumura J.S.
      • Chaturvedi S.
      • Riles T.
      • Ansel G.M.
      • Metzger D.C.
      • et al.
      Randomized trial of stent versus surgery for asymptomatic carotid stenosis.
      or at least six weeks
      • Mannheim D.
      • Karmeli R.
      Prospective randomized trial comparing endarterectomy to stenting in severe asymptomatic carotid stenosis.
      ,
      • Eckstein H.H.
      • Reiff T.
      • Ringleb P.
      • Jansen O.
      • Mansmann U.
      Hacke W for the SPACE 2 Investigators. SPACE-2: a missed opportunity to compare carotid endarterectomy, carotid stenting, and best medical treatment in patients with asymptomatic carotid stenoses.
      post-procedurally in CAS patients. The choice of three days pre-treatment with clopidogrel 75 mg daily (without a loading dose) is based on evidence that clopidogrel’s maximum antiplatelet effect occurs after three to five days of therapy.
      • Quinn M.J.
      • Fitzgerald D.J.
      Ticlopidine and clopidogrel.
      In CREST, aspirin 325 mg twice daily and clopidogrel 75 mg twice daily was recommended for ≥ 48 hours before CAS, followed by aspirin 325 mg daily for 30 days, combined with either clopidogrel 75 mg daily or ticlopidine 250 mg twice daily for at least four weeks.
      • Brott T.G.
      • Howard G.
      • Roubin G.S.
      • Meschia J.F.
      • Mackey A.
      • Brooks W.
      • et al.
      Long-term results of stenting versus endarterectomy for carotid-artery stenosis.
      Patients were not randomised to different APRx regimens in the larger RCTs and ticlopidine is no longer used because of unfavourable side effects.
      Table 5Randomised controlled trials (RCTs) evaluating antiplatelet and intravenous heparin therapy in patients undergoing carotid artery stenting
      StudyStenosis severityMethodAntithrombotic therapyMain findings
      Dalainas
      • Dalainas I.
      • Nano G.
      • Bianchi P.
      • Stegher S.
      • Malacrida G.
      • Tealdi D.G.
      Dual antiplatelet regime versus acetyl-acetic acid for carotid artery stenting.
      70–99%RCT (n = 100; 88 with ACS)325 mg aspirin daily for 7 d pre-CAS + 24 h i.v. heparin post-op, then 325 mg aspirin daily vs. 325 mg aspirin daily + 250 mg ticlopidine twice daily for 7 d pre-CAS and 30 d post-CAS, then 325 mg aspirin dailyAspirin + heparin associated with significant increase in ipsilateral; ischaemic stroke/TIA (16%) vs. 2% (p <.05). No difference in bleeding complications (4 vs. 2%; p >.05)
      McKevitt
      • McKevitt F.M.
      • Randall M.S.
      • Cleveland T.J.
      • Gaines P.A.
      • Tan K.T.
      • Venables G.S.
      The benefits of combined anti-platelet treatment in carotid artery stenting.
      70–99%RCT (n = 47; 9 with ACS)75 mg aspirin daily + 24 h i.v. heparin (APTT ratio 1.5–2.5) vs.75 mg aspirin daily + clopidogrel (300 mg stat 6–12 h pre-op, 75 mg 2 h pre-op + 75 mg daily for days 1–28)Aspirin + heparin associated with significant increase in 30 d ipsilateral amaurosis fugax, TIA, any stroke (25 vs. 0%, p = .02). No difference in incidence of groin haematoma (17 vs. 9%; p = .35)
      ACS = asymptomatic carotid stenosis; TIA = transient ischaemic attack; APTT = activated partial thromboplastin clotting time.

      3.1.3 Combination antiplatelet therapy and direct oral anticoagulants

      The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial randomised 27 395 patients with stable atherosclerotic disease, defined as CAD, peripheral arterial disease (PAD), or carotid disease (prior CEA/CAS or ≥ 50% ACS) to 100 mg enteric coated aspirin daily (n = 9 126), combination low dose rivaroxaban (2.5 mg twice daily) plus 100 mg aspirin daily (n = 9 152) or 5 mg twice daily rivaroxaban (n = 9 117).
      • Eikelboom J.W.
      • Connolly S.J.
      • Bosch J.
      • Dagenais G.R.
      • Hart R.G.
      • Shestakovska O.
      • et al.
      Rivaroxaban with or without aspirin in stable cardiovascular disease.
      After a mean follow up of 23 months, the composite endpoint of stroke, MI, or cardiovascular death was statistically significantly reduced from 5.4% in aspirin patients to 4.1% with low dose rivaroxaban + aspirin (HR 0.76; 95% CI 0.66 – 0.86, p < .001). There was, however, a statistically significantly higher rate of major bleeding complications with combination therapy (3.1% vs. 1.9%: HR 1.7, 95% CI 1.4 – 2.05, p < .001).
      • Eikelboom J.W.
      • Connolly S.J.
      • Bosch J.
      • Dagenais G.R.
      • Hart R.G.
      • Shestakovska O.
      • et al.
      Rivaroxaban with or without aspirin in stable cardiovascular disease.
      Tabled 1
      Recommendation 9Changed
      For patients with >50% asymptomatic carotid stenosis, lower dose aspirin (75–325 mg daily) should be considered, mainly for the prevention of late myocardial infarction and other cardiovascular events.
      ClassLevelReferencesToE
      IIaCKing et al. (2013)
      • King A.
      • Shipley M.
      • Markus H.
      The effect of medical treatments on stroke risk in asymptomatic carotid stenosis.
      , Antithrombotic Trialists Collaboration et al. (2009)
      • Baigent C.
      • Blackwell L.
      • Collins R.
      • Emberson J.
      • Godwin J.
      • et al.
      Antithrombotic Trialists Collaboration
      Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.
      Tabled 1
      Recommendation 10New
      For patients with >50% asymptomatic carotid stenosis who are intolerant or allergic to aspirin, clopidogrel 75 mg daily should be considered. If intolerant or allergic to both aspirin and clopidogrel, dipyridamole monotherapy (200 mg twice daily) should be considered.
      ClassLevelReferencesToE
      IIaCMurphy et al. (2019)
      • Murphy S.J.X.
      • Naylor A.R.
      • Ricco J.B.
      • Sillesen H.
      • Kakkos S.
      • Halliday A.
      • et al.
      Optimal antiplatelet therapy in moderate to severe asymptomatic and symptomatic carotid stenosis: a comprehensive review of the literature.
      Tabled 1
      Recommendation 11New
      For patients with asymptomatic carotid stenosis who are undergoing carotid endarterectomy, lower dose aspirin (75–325 mg daily) rather than higher dose aspirin (>325 mg daily) is recommended.
      ClassLevelReferencesToE
      IBTaylor et al. (1999)
      • Taylor D.W.
      • Barnett H.J.
      • Haynes R.B.
      • Ferguson G.G.
      • Sackett D.L.
      • Thorpe K.E.
      • et al.
      Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy: a randomised controlled trial. ASA and Carotid Endarterectomy (ACE) Trial Collaborators.
      Tabled 1
      Recommendation 12Unchanged
      For patients with asymptomatic carotid stenosis undergoing carotid stenting, combination antiplatelet therapy with aspirin (75–325 mg daily) and clopidogrel (75 mg daily) is recommended. Clopidogrel (75 mg daily) should be started at least three days before stenting or as a single 300 mg loading dose given in urgent cases. Aspirin and clopidogrel should be continued for at least four weeks after stenting and then antiplatelet monotherapy should be continued indefinitely.
      ClassLevelReferencesToE
      IBMurphy et al. (2019)
      • Murphy S.J.X.
      • Naylor A.R.
      • Ricco J.B.
      • Sillesen H.
      • Kakkos S.
      • Halliday A.
      • et al.
      Optimal antiplatelet therapy in moderate to severe asymptomatic and symptomatic carotid stenosis: a comprehensive review of the literature.
      , McKevitt et al. (2005)
      • McKevitt F.M.
      • Randall M.S.
      • Cleveland T.J.
      • Gaines P.A.
      • Tan K.T.
      • Venables G.S.
      The benefits of combined anti-platelet treatment in carotid artery stenting.
      , Mannheim et al. (2017)
      • Mannheim D.
      • Karmeli R.
      Prospective randomized trial comparing endarterectomy to stenting in severe asymptomatic carotid stenosis.
      , Gurm et al. (2008)
      • Gurm H.S.
      • Yadav J.S.
      • Fayad P.
      • Katzen B.T.
      • Mishkel G.J.
      • Bajwa T.K.
      • et al.
      Long-term results of carotid stenting versus endarterectomy in high-risk patients.
      , Rosenfield et al. (2016)
      • Rosenfield K.
      • Matsumura J.S.
      • Chaturvedi S.
      • Riles T.
      • Ansel G.M.
      • Metzger D.C.
      • et al.
      Randomized trial of stent versus surgery for asymptomatic carotid stenosis.
      , Eckstein et al. (2016)
      • Eckstein H.H.
      • Reiff T.
      • Ringleb P.
      • Jansen O.
      • Mansmann U.
      Hacke W for the SPACE 2 Investigators. SPACE-2: a missed opportunity to compare carotid endarterectomy, carotid stenting, and best medical treatment in patients with asymptomatic carotid stenoses.
      , Quinn et al. (1999)
      • Quinn M.J.
      • Fitzgerald D.J.
      Ticlopidine and clopidogrel.

      3.1.4 Lipid lowering therapy

      Tabled 1
      Recommendation 13Changed
      For patients with asymptomatic carotid stenosis, lipid lowering therapy with statins (with or without ezetimibe) is recommended for the long-term prevention of stroke, myocardial infarction, and other cardiovascular events.
      ClassLevelReferencesToE
      IBZhan et al. (2018)
      • Zhan S.
      • Tang M.
      • Liu F.
      • Xia P.
      • Shu M.
      • Wu X.
      Ezetimibe for the prevention of cardiovascular disease and all-cause mortality events.
      , Halliday et al. (2010)
      • Halliday A.
      • Harrison M.
      • Hayter E.
      • Kong X.
      • Mansfield A.
      • Marro J.
      • et al.
      10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial.
      , Cholesterol Treatment Trialists Collaboration (2012)
      Cholesterol Treatment Trialists Collaboration
      The effects of lowering LDL-cholesterol with statin therapy in people at low risk of vascular disease. Meta-analysis of individual data from 27 randomised trials.
      Tabled 1
      Recommendation 14New
      For patients with asymptomatic carotid stenosis with dyslipidaemia who are intolerant of statins, with or without ezetimibe, lipid lowering therapy with PCSK9 inhibitors should be considered.
      ClassLevelReferencesToE
      IIaCGiugliano et al. (2020)
      • Giugliano R.P.
      • Pedersen T.R.
      • Saver J.L.
      • Sever P.S.
      • Keech A.C.
      • Bohula E.A.
      • FOURIER Investigators for
      Stroke prevention with the PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab added to statin in high-risk patients with stable atherosclerosis.
      , Schmidt et al. (2020)
      • Schmidt A.F.
      • Carter J.L.
      • Pearce L.S.
      • Wilkins J.T.
      • Overington J.P.
      • Hingorani A.D.
      • et al.
      PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.

      3.1.5 Management of hypertension

      Tabled 1
      Recommendation 15Unchanged
      For patients with asymptomatic or symptomatic carotid stenoses and hypertension, antihypertensive treatment is recommended.
      ClassLevelReferencesToE
      IAWilliams et al. (2018)
      • Williams B.
      • Mancia G.
      • Spiering W.
      • Agabiti Rosei E.
      • Azizi M.
      • Burnier M.
      • et al.
      ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension.

      3.1.6 Management of diabetes mellitus

      Tabled 1
      Recommendation 16Unchanged
      For diabetic patients with asymptomatic carotid stenoses, optimal glycaemic control is recommended.
      ClassLevelReferencesToE
      IBNICE

      NICE. Type 2 diabetes in adults: management. Available at: https://www.nice.org.uk/guidance/NG28 [Accessed 16 October 2021].

      , NICE

      NICE. Type 1 diabetes in adults: diagnosis and management. Available at: https://www.nice.org.uk/guidance/NG17 [Accessed 16 October 2021].

      , ABCD

      ABCD. Position papers and guidelines. Available at: https://abcd.care/position-papers [Accessed 16 October 2021].

      , American Diabetes Association

      American Diabetes Association. Practice Guidelines Resources. Available at: https://professional.diabetes.org/content-page/practice-guidelines-resources [Accessed 16 October 2021].

      3.1.7 Adherence to medications

      In ACS patients, full adherence to medications is reduced with cognitive impairment, a patient’s lack of insight regarding their illness, a lack of belief in the benefits of prescribed treatments, mental health issues, inadequate follow up or discharge planning, poor doctor patient relationships, barriers to accessing medications, missed appointments, treatment complexity, and drug costs.
      • Kirkpatrick A.C.
      • Vincent A.S.
      • Guthery L.
      • Prodan C.I.
      Cognitive impairment is associated with medication nonadherence in asymptomatic carotid stenosis.
      ,