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Editor's Choice – 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS)

  • Author Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    ,
    Author Footnotes
    ∗ Corresponding authors: Victor Aboyans, Department of Cardiology CHRU Dupuytren Limoges, 2 Avenue Martin Luther King, 87042 Limoges, France. Tel: +33 5 55 05 63 10, Fax: +33 5 55 05 63 34, Email: [email protected]. Jean-Baptiste Ricco, Department of Vascular Surgery, University Hospital, rue de la Miletrie, 86021 Poitiers, France. Tel: +33 549443846, Fax: +33 5 49 50 05 50, Email: [email protected]
    Victor Aboyans
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    ∗ Corresponding authors: Victor Aboyans, Department of Cardiology CHRU Dupuytren Limoges, 2 Avenue Martin Luther King, 87042 Limoges, France. Tel: +33 5 55 05 63 10, Fax: +33 5 55 05 63 34, Email: [email protected]. Jean-Baptiste Ricco, Department of Vascular Surgery, University Hospital, rue de la Miletrie, 86021 Poitiers, France. Tel: +33 549443846, Fax: +33 5 49 50 05 50, Email: [email protected]
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  • Author Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    ,
    Author Footnotes
    ∗ Corresponding authors: Victor Aboyans, Department of Cardiology CHRU Dupuytren Limoges, 2 Avenue Martin Luther King, 87042 Limoges, France. Tel: +33 5 55 05 63 10, Fax: +33 5 55 05 63 34, Email: [email protected]. Jean-Baptiste Ricco, Department of Vascular Surgery, University Hospital, rue de la Miletrie, 86021 Poitiers, France. Tel: +33 549443846, Fax: +33 5 49 50 05 50, Email: [email protected]
    Jean-Baptiste Ricco
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    ∗ Corresponding authors: Victor Aboyans, Department of Cardiology CHRU Dupuytren Limoges, 2 Avenue Martin Luther King, 87042 Limoges, France. Tel: +33 5 55 05 63 10, Fax: +33 5 55 05 63 34, Email: [email protected]. Jean-Baptiste Ricco, Department of Vascular Surgery, University Hospital, rue de la Miletrie, 86021 Poitiers, France. Tel: +33 549443846, Fax: +33 5 49 50 05 50, Email: [email protected]
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  • Author Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Marie-Louise E.L. Bartelink
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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  • Author Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Martin Björck
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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  • Author Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Marianne Brodmann
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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  • Author Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Tina Cohnert
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Jean-Philippe Collet
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Martin Czerny
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Marco De Carlo
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Sebastian Debus
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Christine Espinola-Klein
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Thomas Kahan
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Serge Kownator
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Lucia Mazzolai
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    A. Ross Naylor
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Marco Roffi
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Joachim Röther
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Muriel Sprynger
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Michal Tendera
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Gunnar Tepe
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Maarit Venermo
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Charalambos Vlachopoulos
    Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    Ileana Desormais
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    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
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    b Document Reviewers: Petr Widimsky (ESC Review Coordinator) (Czech Republic), Philippe Kolh (ESVS Review Coordinator) (Belgium), Stefan Agewall (Norway), Héctor Bueno (Spain), Antonio Coca (Spain), Gert J. De Borstc (The Netherlands), Victoria Delgado (The Netherlands), Florian Dickc (Switzerland), Cetin Erol (Turkey), Marc Ferrini (France), Stavros Kakkosc (Greece/UK), Hugo A. Katus (Germany), Juhani Knuuti (Finland), Jes Lindholtc (Denmark), Heinrich Mattled (Switzerland), Piotr Pieniazek (Poland), Massimo Francesco Piepoli (Italy), Dierk Scheinert (Germany), Horst Sievert (Germany), Iain Simpson (UK), Jakub Sulzenko (Czech Republic), Juan Tamargo (Spain), Lale Tokgozoglu (Turkey), Adam Torbicki (Poland), Nikolaos Tsakountakis (Greece), José Tuñón (Spain), Melina Vega de Cenigac (Spain), Stephan Windecker (Switzerland), Jose Luis Zamorano (Spain)
    Document Reviewers
    Footnotes
    b Document Reviewers: Petr Widimsky (ESC Review Coordinator) (Czech Republic), Philippe Kolh (ESVS Review Coordinator) (Belgium), Stefan Agewall (Norway), Héctor Bueno (Spain), Antonio Coca (Spain), Gert J. De Borstc (The Netherlands), Victoria Delgado (The Netherlands), Florian Dickc (Switzerland), Cetin Erol (Turkey), Marc Ferrini (France), Stavros Kakkosc (Greece/UK), Hugo A. Katus (Germany), Juhani Knuuti (Finland), Jes Lindholtc (Denmark), Heinrich Mattled (Switzerland), Piotr Pieniazek (Poland), Massimo Francesco Piepoli (Italy), Dierk Scheinert (Germany), Horst Sievert (Germany), Iain Simpson (UK), Jakub Sulzenko (Czech Republic), Juan Tamargo (Spain), Lale Tokgozoglu (Turkey), Adam Torbicki (Poland), Nikolaos Tsakountakis (Greece), José Tuñón (Spain), Melina Vega de Cenigac (Spain), Stephan Windecker (Switzerland), Jose Luis Zamorano (Spain)
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  • Author Footnotes
    a Authors/Task Force Members: Victor Aboyans∗ (ESC Chairperson) (France), Jean-Baptiste Ricco∗c (Co-Chairperson) (France), Marie-Louise E. L. Bartelink (The Netherlands), Martin Björckc (Sweden), Marianne Brodmann (Austria), Tina Cohnertc (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debusc (Germany), Christine Espinola-Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylorc (UK), Marco Roffi (Switzerland), Joachim Rötherd (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermoc (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France)
    b Document Reviewers: Petr Widimsky (ESC Review Coordinator) (Czech Republic), Philippe Kolh (ESVS Review Coordinator) (Belgium), Stefan Agewall (Norway), Héctor Bueno (Spain), Antonio Coca (Spain), Gert J. De Borstc (The Netherlands), Victoria Delgado (The Netherlands), Florian Dickc (Switzerland), Cetin Erol (Turkey), Marc Ferrini (France), Stavros Kakkosc (Greece/UK), Hugo A. Katus (Germany), Juhani Knuuti (Finland), Jes Lindholtc (Denmark), Heinrich Mattled (Switzerland), Piotr Pieniazek (Poland), Massimo Francesco Piepoli (Italy), Dierk Scheinert (Germany), Horst Sievert (Germany), Iain Simpson (UK), Jakub Sulzenko (Czech Republic), Juan Tamargo (Spain), Lale Tokgozoglu (Turkey), Adam Torbicki (Poland), Nikolaos Tsakountakis (Greece), José Tuñón (Spain), Melina Vega de Cenigac (Spain), Stephan Windecker (Switzerland), Jose Luis Zamorano (Spain)
    ∗ Corresponding authors: Victor Aboyans, Department of Cardiology CHRU Dupuytren Limoges, 2 Avenue Martin Luther King, 87042 Limoges, France. Tel: +33 5 55 05 63 10, Fax: +33 5 55 05 63 34, Email: [email protected]. Jean-Baptiste Ricco, Department of Vascular Surgery, University Hospital, rue de la Miletrie, 86021 Poitiers, France. Tel: +33 549443846, Fax: +33 5 49 50 05 50, Email: [email protected]
    c Representing the European Society for Vascular Surgery (ESVS)
    d Representing the European Stroke Organisation (ESO)
Open ArchivePublished:August 25, 2017DOI:https://doi.org/10.1016/j.ejvs.2017.07.018

      Keywords

      Abbreviations and acronyms

      AAA
      abdominal aorta aneurysm
      ABI
      ankle-brachial index
      ACAS
      Asymptomatic Carotid Atherosclerosis Study
      ACEIs
      angiotensin-converting enzyme inhibitors
      ACS
      acute coronary syndrome
      ACSRS
      asymptomatic carotid atherosclerosis risk of stroke
      ACST
      Asymptomatic Carotid Surgery Trial
      ACT
      Asymptomatic Carotid Trial
      AF
      atrial fibrillation
      AMERICA
      Aggressive detection and Management of the Extension of atherothrombosis in high Risk coronary patients In comparison with standard of Care for coronary Atherosclerosis
      ARBs
      angiotensin-receptor blockers
      ARR
      absolute risk reduction
      ASTRAL
      angioplasty and stenting for renal artery lesions
      BASIL
      bypass versus angioplasty in severe ischaemia of the leg
      BEST-CLI
      Best Endovascular vs. Best Surgical Therapy in Patients with Critical Limb Ischaemia
      BMT
      best medical therapy
      BP
      blood pressure
      CABG
      coronary artery bypass grafting
      CAD
      coronary artery disease
      CAPRIE
      Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events
      CAPTURE
      Carotid ACCULINK/ACCUNET Post-Approval Trial to Uncover Rare Events
      CARESS
      Clopidogrel and Aspirin for the Reduction of Emboli in Symptomatic carotid Stenosis
      CASPAR
      Clopidogrel and Acetylsalicylic Acid in Bypass Surgery for Peripheral Arterial disease
      CAS
      carotid artery stenting
      CCA
      common carotid artery
      CEA
      carotid endarterectomy
      CFA
      common femoral artery
      CHA2DS2-VASc
      Congestive heart failure, Hypertension, Age ≥75 (2 points), Diabetes mellitus, Stroke or TIA (2 points), Vascular disease, Age 65–74 years, Sex category
      CHARISMA
      Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance
      CI
      confidence interval
      CKD
      chronic kidney disease
      CLEVER
      Claudication: exercise versus endoluminal revascularization
      CLTI
      Chronic limb-threatening ischaemia
      CMI
      chronic mesenteric ischaemia
      CONFIRM
      Coronary CT Angiography Evaluation for Clinical Outcomes: an International Multicenter
      CORAL
      Cardiovascular Outcomes in Renal Atherosclerotic Lesions
      CPB
      cardiopulmonary bypass
      CPG
      Committee for Practice Guidelines
      CREST
      Carotid Revascularization Endarterectomy versus Stenting Trial
      CTA
      computed tomography angiography
      CV
      cardiovascular
      DAPT
      dual antiplatelet therapy
      DES
      drug eluting stent
      DSA
      digital subtraction angiography
      DUS
      duplex ultrasound
      ECG
      electrocardiogram
      ECST
      European Carotid Surgery Trial
      EPD
      embolus protection device
      ESC
      European Society of Cardiology
      ESO
      European Stroke Organisation
      ESVS
      European Society of Vascular Surgery
      EUCLID
      Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease
      EVA-3S
      Endarterectomy vs Stenting in Patients with Symptomatic Severe Carotid Stenosis
      EVT
      endovascular therapy
      ExT
      exercise therapy
      FMD
      fibromuscular dysplasia
      GSV
      great saphenous vein
      HDL-C
      high-density lipoprotein cholesterol
      HF-ACTION
      Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training
      HITS
      high-intensity transient signal
      HOPE
      Heart Outcomes Prevention Trial
      HR
      hazard ratio
      IC
      intermittent claudication
      ICA
      internal carotid artery
      ICD
      implantable cardioverter defibrillator
      ICSS
      International Carotid Stenting Study
      INR
      international normalized ratio
      INVEST
      INternational VErapamil-SR/Trandolapril Study
      LDL-C
      low-density lipoprotein cholesterol
      LEAD
      lower extremity artery disease
      LV
      left ventricular
      MACE
      major adverse cardiovascular event
      MI
      myocardial infarction
      MRA
      magnetic resonance angiography
      MR CLEAN
      MultiCenter Randomized Clinical Trial of Ischemic Stroke in the Netherlands
      MRI
      magnetic resonance imaging
      MSAD
      multisite artery disease
      MWD
      maximal walking distance
      NASCET
      North American Symptomatic Carotid Endarterectomy Trial
      NNH
      number needed to harm
      NNT
      number needed to treat
      NOAC
      non-vitamin K oral anticoagulant
      OAC
      oral anticoagulation
      ONTARGET
      Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial
      OR
      odds ratio
      PADs
      peripheral arterial diseases
      PCI
      percutaneous coronary intervention
      PEGASUS-TIMI 54
      Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54
      PRODIGY
      PROlonging Dual antiplatelet treatment after Grading stent-induced intimal hYperplasia study
      PTA
      percutaneous transluminal angioplasty
      QOL
      quality of life
      RAAS
      renin–angiotensin–aldosterone system
      RAD
      renal artery disease
      RAS
      renal artery stenosis
      RCT
      randomized clinical trial
      REACH
      Reduction of Atherothrombosis for Continued Health
      ROCKET-AF
      Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation
      RR
      relative risk
      RRI
      renal resistive index
      SAPPHIRE
      Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy
      SAPT
      single antiplatelet therapy
      SBP
      systolic blood pressure
      SFA
      superficial femoral artery
      SPACE
      Stent Protected Angioplasty versus Carotid Endarterectomy
      STAR
      Stent Placement in Patients With Atherosclerotic Renal Artery Stenosis and Impaired Renal Function
      TAMARIS
      Efficacy and Safety of XRP0038/NV1FGF in Critical Limb Ischaemia Patients With Skin Lesions
      TAVI
      transcatheter aortic valve implantation
      TBI
      toe-brachial index
      TcPO2
      transcutaneous oxygen pressure
      TIA
      transient ischaemic attack
      TTE
      transthoracic echocardiography
      UEAD
      upper extremity artery disease
      VA
      vertebral artery
      VAST
      Vertebral Artery Stenting Trial
      VHD
      valvular heart disease
      VKA
      vitamin K antagonist
      WD
      walking distance
      WIfI
      wound, ischaemia and foot infection

      1. Preamble

      Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in selecting the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.
      A great number of guidelines have been issued in recent years by the European Society of Cardiology (ESC), by the European Society of Vascular Surgery (ESVS) and by the European Stroke Organization (ESO), as well as by other societies and organisations. Because of the impact on clinical practice, quality criteria for the development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines can be found on the ESC Website (https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Guidelines-development/Writing-ESC-Guidelines). ESC Guidelines represent the official position of the ESC on a given topic and are regularly updated.
      Members of this Task Force were selected by the ESC, including representation from the ESVS and ESO to represent professionals involved with the medical care of patients with this pathology. Selected experts in the field undertook a comprehensive review of the published evidence for management of a given condition according to ESC Committee for Practice Guidelines (CPG) policy and approved by the ESVS and ESO. A critical evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk–benefit ratio. The level of evidence and the strength of the recommendation of particular management options were weighed and graded according to predefined scales, as outlined in Table 1, Table 2.
      Table 1Classes of recommendations.
      Table thumbnail fx1
      Table 2Levels of evidence.
      Level of evidence AData derived from multiple randomized clinical trials or meta-analyses.
      Level of evidence BData derived from a single randomized clinical trial or large non-randomized studies.
      Level of evidence CConsensus of opinion of the experts and/or small studies, retrospective studies, registries.
      The experts of the writing and reviewing panels provided declaration of interest forms for all relationships that might be perceived as real or potential sources of conflicts of interest. These forms were compiled into one file and can be found on the ESC Website (http://www.escardio.org/guidelines). Any changes in declarations of interest that arise during the writing period were notified to the ESC and updated. The Task Force received its entire financial support from the ESC and ESVS without any involvement from the healthcare industry.
      The ESC CPG supervises and coordinates the preparation of new Guidelines. The Committee is also responsible for the endorsement process of these Guidelines. The ESC Guidelines undergo extensive review by the CPG and external experts, and in this case by ESVS- and ESO-appointed experts. After appropriate revisions the Guidelines are approved by all the experts involved in the Task Force. The finalized document is approved by the CPG and ESVS for publication in the European Heart Journal and in the European Journal of Vascular and Endovascular Surgery. The Guidelines were developed after careful consideration of the scientific and medical knowledge and the evidence available at the time of their dating.
      The task of developing ESC Guidelines in collaboration with ESVS also includes the creation of educational tools and implementation programmes for the recommendations including condensed pocket guideline versions, summary slides, booklets with essential messages, summary cards for non-specialists and an electronic version for digital applications (smartphones, etc.). These versions are abridged and thus, if needed, one should always refer to the full text version, which is freely available via the ESC Website and hosted on the EHJ Website. The National Societies of the ESC are encouraged to endorse, translate and implement all ESC Guidelines. Implementation programmes are needed because it has been shown that the outcome of disease may be favourably influenced by the thorough application of clinical recommendations.
      Surveys and registries are needed to verify that real-life daily practice is in keeping with what is recommended in the guidelines, thus completing the loop between clinical research, writing of guidelines, disseminating them and implementing them into clinical practice.
      Health professionals are encouraged to take the ESC Guidelines developed in collaboration with ESVS fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies. However, the ESC Guidelines do not override in any way whatsoever the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient or the patient's caregiver where appropriate and/or necessary. It is also the health professional's responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.

      2. Introduction

      In 2011, the ESC published its first Guidelines on the Diagnosis and Management of Peripheral Arterial Diseases.
      • Tendera M.
      • Aboyans V.
      • Bartelink M.L.
      • Baumgartner I.
      • Clement D.
      • Collet J.P.
      • et al.
      ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC).
      This publication filled an important gap within the ESC Guidelines documents compendium. Meanwhile, the ESVS released on a regular basis several guidelines documents on the management of specific localizations of arterial diseases.
      Both societies emphasized the need for multidisciplinary management of these patients. When the decision was made to update these guidelines, it appeared obvious that a combination of efforts from both societies would provide the most comprehensive single document, providing updated guidelines on peripheral arterial diseases (PADs) for clinicians.
      It is of the outmost importance that every cardiologist should be sensitive in regard to the diagnosis and management of patients with PADs, as many of them are seen and managed for concomitant cardiac conditions. In the ESC 2011 Guidelines, a specific chapter was dedicated to patients with combined coronary and peripheral artery diseases, as they mostly share the same aetiology and risk factors. In these guidelines, the Task Force made a step forward and proposed a new chapter on other cardiac conditions frequently encountered among patients with PADs. Also, as the options for the use and combination of antithrombotic drugs have increased, a specific chapter has been dedicated to their use in the management of PADs.
      In this document, the term ‘peripheral arterial diseases’ encompasses all arterial diseases other than coronary arteries and the aorta. This should be clearly distinguished from the term ‘peripheral artery disease’, which is often used for lower extremity artery disease (LEAD). Indeed, other peripheral localizations, including the carotid and vertebral, upper extremities, mesenteric and renal arteries, are also frequently affected, mainly by atherosclerosis, and complete the family of PADs. Regarding the carotid and vertebral arteries, this document covers only their extracranial segments, as specialists other than cardiologists and vascular surgeons often manage intracranial arterial diseases.
      The Task Force has decided to address only PADs secondary to atherosclerosis, with a few exceptions in specific areas where non-atherosclerotic diseases are a frequent differential diagnosis (e.g. fibromuscular dysplasia in renal arteries). For other cases, readers should always bear in mind the possibility for non-atherosclerotic conditions and refer to specific documents. Readers are also invited to refer to the Web addenda for further information.
      The ESC and ESVS also join their efforts to provide increased medical and public awareness about PADs. Indeed, while stroke is acknowledged as a serious condition with significant burden throughout Europe, other PADs can be as lethal and disabling. Major efforts are still necessary to sensitize healthcare providers, decision makers and the general population about the need for earlier and more efficient prevention and management strategies for the 40 million individuals of our continent affected by PADs.
      • Tendera M.
      • Aboyans V.
      • Bartelink M.L.
      • Baumgartner I.
      • Clement D.
      • Collet J.P.
      • et al.
      ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC).
      • Fowkes F.G.
      • Rudan D.
      • Rudan I.
      • Aboyans V.
      • Denenberg J.O.
      • McDermott M.M.
      • et al.
      Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis.
      Tabled 1
      Table thumbnail fx9
      Tabled 1General recommendations on the management of patients with peripheral arterial diseases
      Table thumbnail fx10
      PADs = peripheral arterial diseases.
      aClass of recommendation.
      bLevel of evidence

      3. Epidemiology and risk factors

      • Overall, the risk of different localizations of PADs increases sharply with age and with exposure to major cardiovascular (CV) risk factors, including smoking, hypertension, dyslipidaemia and diabetes. Other risk factors are still under investigation.
      • The strength of association between each risk factor and each vascular territory is variable, but all the major risk factors should be screened and considered.
      • When a vascular territory is affected by atherosclerosis, not only is the corresponding organ endangered [e.g. the brain for carotid artery disease (CAD)], but also the total risk of any CV event is increased (e.g. coronary events). Each vascular territory affected by atherosclerosis can be considered as marker of CV risk.

      3.1 Epidemiology

      The epidemiology of different patterns of PADs is presented in the Web addenda 3.1.

      3.2 Risk factors

      Although different localizations of PADs share common major risk factors for atherosclerosis, the impact of those and/or available evidence differ per arterial site. See Web addenda 3.2.

      3.3 Prognosis

      Atherosclerosis is often generalized. Patients affected at one site are overall at risk for fatal and non-fatal CV events.
      Beyond the risk of cerebrovascular events, patients with CAD are also at risk for myocardial infarction (MI) and cardiac death.
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      • Nicolaides A.N.
      • Ramaswami G.
      • Cesarone M.R.
      • De Sanctis M.
      • Incandela L.
      • et al.
      Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: a 10-year follow-up study (the CAFES-CAVE study).
      In a systematic review of 17 studies including 11 391 patients with >50% asymptomatic carotid stenosis, 63% of late deaths were related to cardiac events, with a mean cardiac-related mortality rate of 2.9%/year.
      • 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.
      Many studies have shown an increased risk of mortality, CV mortality and morbidity (MI, stroke) in patients with symptomatic or asymptomatic LEAD, even after adjustment for conventional risk factors.
      • Criqui M.H.
      • Aboyans V.
      Epidemiology of peripheral artery disease.
      An ankle-brachial index (ABI) ≤0.90 is associated with more than doubling of the 10-year rates of coronary events, CV mortality and total mortality.
      • Fowkes F.G.
      • Murray G.D.
      • Butcher I.
      • Heald C.L.
      • Lee R.J.
      • Chambless L.E.
      • et al.
      Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.
      After 5 years, 20% of patients with intermittent claudication (IC) present an MI or stroke and mortality is 10–15%.
      • Weitz J.I.
      • Byrne J.
      • Clagett G.P.
      • Farkouh M.E.
      • Porter J.M.
      • Sackett D.L.
      • et al.
      Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review.
      All these data emphasize the importance of general CV prevention beyond the management of the disease related to a specific site of atherosclerosis.

      4. General aspects

      • Thorough clinical history and physical examination are key steps in PADs management.
      • Beyond the diagnosis of LEAD, ABI is also a strong marker for CV events.
      • The management of PADs includes all interventions to address specific arterial symptoms as well as general CV risk prevention.
      • Best medical therapy includes CV risk factor management, including optimal pharmacological therapy as well as non-pharmacological measures such as smoking cessation, healthy diet, weight loss and regular physical exercise.

      4.1 Diagnostic approach

      4.1.1 Clinical history

      Personal and family clinical history should always be assessed. Family history includes CAD, cerebrovascular disease, aortic aneurysm as well as LEAD.
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      • Guerra R.
      • Stephan P.
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      • Clagett G.P.
      • Cohen J.
      Family history is a major determinant of subclinical peripheral arterial disease in young adults.
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      • Loomba R.
      • Ix J.H.
      • Allison M.A.
      • Denenberg J.O.
      • Criqui M.H.
      Family history of peripheral artery disease is associated with prevalence and severity of peripheral artery disease: the San Diego population study.
      • Khaleghi M.
      • Isseh I.N.
      • Bailey K.R.
      • Kullo I.J.
      Family history as a risk factor for peripheral arterial disease.
      Clinical history includes the evaluation of CV risk factors and comorbidities as well as a review of the symptoms related to different vascular territories (see Web Table 1). Lifestyle habits, dietary patterns, walking performances and physical activity need to be systematically interrogated. Physical activity should be assessed.
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      • Carre F.
      • Heuschmann P.
      • Hoffmann U.
      • Verschuren M.
      • et al.
      Secondary prevention through cardiac rehabilitation: physical activity counselling and exercise training: key components of the position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation.
      Questionnaires and functional status provide reasonably accurate outcome measures. They may be useful for determining the impairment level and selection of appropriate care.
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      • et al.
      International physical activity questionnaire: 12-country reliability and validity.
      • Washburn R.A.
      • Smith K.W.
      • Jette A.M.
      • Janney C.A.
      The Physical Activity Scale for the Elderly (PASE): development and evaluation.

      4.1.2 Clinical examination

      Although physical examination alone is of relatively poor sensitivity and reproducibility, a systematic approach is mandatory (see Web Table 2). Beyond their diagnostic importance, clinical signs have a prognostic value. Individuals with carotid bruits have twice the risk of MI and CV death as compared with those without.
      • Pickett C.A.
      • Jackson J.L.
      • Hemann B.A.
      • Atwood J.E.
      Carotid bruits as a prognostic indicator of cardiovascular death and myocardial infarction: a meta-analysis.
      Interarm blood pressure (BP) asymmetry (≥15 mmHg) is a marker of vascular disease risk and death.
      • Clark C.E.
      • Taylor R.S.
      • Shore A.C.
      • Ukoumunne O.C.
      • Campbell J.L.
      Association of a difference in systolic blood pressure between arms with vascular disease and mortality: a systematic review and meta-analysis.
      A femoral bruit is an independent marker for ischaemic cardiac events.
      • Cournot M.
      • Taraszkiewicz D.
      • Cambou J.P.
      • Galinier M.
      • Boccalon H.
      • Hanaire-Broutin H.
      • et al.
      Additional prognostic value of physical examination, exercise testing, and arterial ultrasonography for coronary risk assessment in primary prevention.

      4.1.3 Laboratory testing

      Investigations should progress from the ‘minimal’ biological assessment
      • Vlachopoulos C.
      • Xaplanteris P.
      • Aboyans V.
      • Brodmann M.
      • Cifkova R.
      • Cosentino F.
      • et al.
      The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society.
      to complementary laboratory tests if necessary (outlined in Web Table 3).

      4.1.4 Diagnostic methods for PADs

      4.1.4.1 Ankle-brachial index

      The ABI is a non-invasive tool useful for the diagnosis and surveillance of LEAD. It is also a strong marker of generalized atherosclerosis and CV risk (see Table 3). An ABI ≤0.90 is associated on average with a 2- to 3-fold increased risk of total and CV death. An ABI >1.40 represents arterial stiffening (medial arterial calcification) and is also associated with a higher risk of CV events and mortality.
      • Fowkes F.G.
      • Murray G.D.
      • Butcher I.
      • Heald C.L.
      • Lee R.J.
      • Chambless L.E.
      • et al.
      Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.
      • Criqui M.H.
      • McClelland R.L.
      • McDermott M.M.
      • Allison M.A.
      • Blumenthal R.S.
      • Aboyans V.
      • et al.
      The ankle-brachial index and incident cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis).
      It is more prevalent in elderly patients, mostly in those with diabetes or chronic kidney disease (CKD). When added to a risk score, ABI enables the risk estimation to be upgraded in one-third and one-fifth of ‘low-risk’ women and men, respectively.
      • Fowkes F.G.
      • Murray G.D.
      • Butcher I.
      • Heald C.L.
      • Lee R.J.
      • Chambless L.E.
      • et al.
      Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis.
      It is a valid method of CV risk assessment in diverse ethnic groups, independent of risk factors.
      • Criqui M.H.
      • McClelland R.L.
      • McDermott M.M.
      • Allison M.A.
      • Blumenthal R.S.
      • Aboyans V.
      • et al.
      The ankle-brachial index and incident cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis).
      In contrast to coronary calcium score and carotid intima-media thickness, ABI is inexpensive and minimally time consuming. Good training is mandatory.
      Table 3The Ankle-Brachial Index.
      1. Who should have an ABI measurement in clinical practice?
      • Patients with clinical suspicion for LEAD:
        • Lower extremities pulse abolition and/or arterial bruit
        • Typical intermittent claudication or symptoms suggestive for LEAD
        • Non-healing lower extremity wound
      • Patients at risk for LEAD because of the following clinical conditions:
        • Atherosclerotic diseases: CAD, any PADs
        • Other conditions: AAA, CKD, heart failure
      • Asymptomatic individuals clinically-free but at-risk for LEAD:
        • Men and women aged >65 years
        • Men and women aged <65 years classified at high CV risk according the ESC Guidelines
          Subjects with: markedly elevated single risk factors; diabetes mellitus (except for young people with type 1 diabetes without other major risk factors); a calculated SCORE ≥5% and <10%.
        • Men and women aged >50 years with family history for LEAD
      2. How to measure the ABI?
      • In supine position, with cuff placed just above the ankle, avoiding wounded zones. After a 5–10 minute rest, the SBP is measured by a Doppler probe (5–10 MHz) on the posterior and the anterior tibial (or dorsal pedis) arteries of each foot and on the brachial artery of each arm. Automated BP cuffs are mostly not valid for ankle pressure and may display overestimated results in case of low ankle pressure. The ABI of each leg is calculated by dividing the highest ankle SBP by the highest arm SBP.
        Image 2
      3. How to interpret the ABI?
      AAA = abdominal aorta aneurysm; ABI = ankle-brachial index; BP = blood pressure; CAD = coronary artery disease; CKD = chronic kidney disease; CV = cardiovascular; ESC = European Society of Cardiology; LEAD = lower extremity artery disease; PADs = peripheral arterial diseases; SBP = systolic blood pressure.
      a Subjects with: markedly elevated single risk factors; diabetes mellitus (except for young people with type 1 diabetes without other major risk factors); a calculated SCORE ≥5% and <10%.
      In addition to the general CV risk, ABI measurement can identify a patient's risk for lower-extremities events, requiring close attention and education for foot wound prevention.

      4.1.4.2 Duplex ultrasound

      Duplex ultrasound (DUS) is often a first step in the vascular workup both for screening and diagnosis. DUS includes B-mode echography, pulsed-wave, continuous, colour and power Doppler modalities to detect and localize vascular lesions and quantify their extent and severity through velocity criteria. More recent techniques, such as flow imaging or live three-dimensional (3D) echography, as well as the use of ultrasound contrast agents, further improve DUS performances, although their use is still limited. DUS can detect subclinical artery disease (e.g. carotid plaque), which is important for CV risk assessment.
      • Vlachopoulos C.
      • Xaplanteris P.
      • Aboyans V.
      • Brodmann M.
      • Cifkova R.
      • Cosentino F.
      • et al.
      The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society.

      4.1.4.3 Digital subtraction angiography

      Digital subtraction angiography (DSA) was considered the standard reference in vascular imaging. Given its invasive character and risk of complications, it has been mostly replaced by other less invasive methods except for below-the-knee arterial disease. It may be used in the case of discrepancy between non-invasive imaging tools.

      4.1.4.4 Computed tomography angiography

      Multidetector computed tomography angiography (CTA) has a short examination time with reduced motion and respiration artefacts while imaging vessels and organs. Advantages of CTA include rapid non-invasive acquisition, wide availability, high resolution and 3D reformatting. Similar to DSA and magnetic resonance angiography (MRA), CTA displays a ‘roadmap’ of the vascularization, essential for determining interventional strategies (lesion localization and severity, upstream/downstream status). The drawbacks of CTA include the lack of functional and haemodynamic data, exposure to radiation and the use of iodinated contrast agents, which should be limited in the case of CKD, with precautions in case of allergies. Nephrotoxicity can be limited by minimizing contrast agent volume and ensuring adequate hydration before and after imaging. The benefit of acetyl-cysteine to limit nephrotoxicity is uncertain.
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      • Hsiang H.F.
      • Wong C.S.
      • Yao M.S.
      • Li Y.W.
      • Hsiang C.Y.
      • et al.
      The effectiveness of N-acetylcysteine in preventing contrast-induced nephropathy in patients undergoing contrast-enhanced computed tomography: a meta-analysis of randomized controlled trials.
      • O'Sullivan S.
      • Healy D.A.
      • Moloney M.C.
      • Grace P.A.
      • Walsh S.R.
      The role of N-acetylcysteine in the prevention of contrast-induced nephropathy in patients undergoing peripheral angiography: a structured review and meta-analysis.
      Recent studies have suggested that statins or sodium bicarbonate could prevent contrast agent nephrotoxicity.
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      • Burgess W.P.
      • Gray L.V.
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      • et al.
      Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial.
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      • Yaylak B.
      • Altay S.
      • Kasikcioglu H.
      • Cam N.
      The role of statins in preventing contrast-induced acute kidney injury: a narrative review.
      Further research is required.

      4.1.4.5 Magnetic resonance angiography

      MRA is used for peripheral artery imaging using contrast (i.e. gadolinium) and non-contrast techniques (i.e. phase contrast and time-of-flight sequences). These latter techniques have inferior resolution and are susceptible to artefacts, limiting their interpretation. They are a valuable alternative for use in patients with mild to moderate CKD. Compared with CTA, MRA does not need iodine contrast and has higher soft tissue resolution; however, motion artefacts are more frequent and contraindications include pacemakers and implantable cardioverter defibrillators (ICDs) [except magnetic resonance imaging (MRI)-conditional and compatible pacemakers, ICDs and leads], claustrophobia and severe CKD. In the latter case, the risk of nephrogenic systemic fibrosis following gadolinium administration should not be underestimated.
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      • Ramalho M.
      • Nunes R.H.
      • AlObaidy M.
      • Castillo M.
      Gadolinium-based contrast agent accumulation and toxicity: an update.
      Vascular calcifications, potentially affecting revascularization procedures, can be underestimated. Endovascular stents are not evaluable by MRI.

      4.2 Treatment approach

      The therapeutic approach to patients with PADs includes two aspects. The first is to address specific symptoms of any localization and the risk related to a specific lesion. This is addressed in the next sections.
      The second aspect of management in these patients is related to their increased risk of any CV event (see section 3.2). General CV prevention is of the utmost importance and management should be multidisciplinary. Best medical therapy (BMT) includes CV risk factor management, including best pharmacological therapy, as well as non-pharmacological measures such as smoking cessation, healthy diet, weight loss and regular physical exercise.
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      2016 European Guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR).
      The pharmacological component of BMT includes antihypertensive, lipid-lowering and antithrombotic drugs. In diabetic patients, optimal glucose level control should be obtained as recommended.
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      • et al.
      ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD).

      4.2.1 Smoking cessation

      A body of evidence supports the benefits of smoking cessation in reducing CV events and mortality, especially in patients with cerebrovascular disease and LEAD.
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      Impact of tobacco smoking and smoking cessation on cardiovascular risk and disease.
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      • et al.
      A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010.
      Management and support for smoking cessation was extensively addressed in the 2016 ESC guidelines on CV disease prevention.
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      • et al.
      2016 European Guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR).
      Passive smoking should be assessed and prevented.
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      4.2.2 Lipid-lowering drugs

      All patients with PADs should have their serum low-density lipoprotein cholesterol (LDL-C) reduced to <1.8 mmol/L (<70 mg/dL) or decreased by ≥50% if the initial LDL-C level is between 1.8 and 3.5 mmol/L (70 and 135 mg/dL).
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      • Catapano A.L.
      • et al.
      2016 European Guidelines on cardiovascular disease prevention in clinical practice: the Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR).
      In observational studies and limited randomized clinical trials (RCTs) in patients with LEAD (from asymptomatic to severe cases), statin therapy has been shown to cause reductions in all-cause mortality and CV events.
      • Aung P.P.
      • Maxwell H.G.
      • Jepson R.G.
      • Price J.F.
      • Leng G.C.
      Lipid-lowering for peripheral arterial disease of the lower limb.
      • Antoniou G.A.
      • Fisher R.K.
      • Georgiadis G.S.
      • Antoniou S.A.
      • Torella F.
      Statin therapy in lower limb peripheral arterial disease: systematic review and meta-analysis.
      • Heart Protection Study Collaborative Group
      Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions.
      In the Reduction of Atherothrombosis for Continued Health (REACH) registry, among patients with LEAD, statin use was associated with a 17% decrease in adverse CV events rates.
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      • Steg P.G.
      • Cannon C.P.
      • Eagle K.A.
      • Smith Jr., S.C.
      • Goto S.
      • et al.
      Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry.
      Even in the most advanced stages of disease, statin therapy is associated with lower 1-year rates of mortality and major CV adverse events.
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      • Armstrong E.J.
      • Bang H.
      • Yeo K.K.
      • Anderson D.
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      • et al.
      Association between statin medications and mortality, major adverse cardiovascular event, and amputation-free survival in patients with critical limb ischemia.
      Combination treatment with ezetimibe in selected patients is also beneficial.
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      • Blazing M.A.
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      • White J.A.
      • Lokhnygina Y.
      • et al.
      Reduction in total cardiovascular events with ezetimibe/simvastatin post-acute coronary syndrome: the IMPROVE-IT Trial.
      In a randomized trial, bezafibrate showed no benefit over placebo to reduce coronary and cerebrovascular events in patients with LEAD.
      • Meade T.
      • Zuhrie R.
      • Cook C.
      • Cooper J.
      Bezafibrate in men with lower extremity arterial disease: randomised controlled trial.
      In those with CAD, statins reduce the stroke risk.
      • Amarenco P.
      • Labreuche J.
      • Lavallee P.
      • Touboul P.J.
      Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis.
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      • Li R.
      • Wu Y.
      Effect of statin therapy on the progression of common carotid artery intima-media thickness: an updated systematic review and meta-analysis of randomized controlled trials.
      Recently the Fourier trial demonstrated the additional benefits of evolocumab, a monoclonal antibody inhibiting the proprotein convertase subtilisin/kexin type 9 to reduce CV events in patients with atherosclerotic disease over statins alone.
      • Sabatine M.S.
      • Giugliano R.P.
      • Keech A.C.
      • Honarpour N.
      • Wiviott S.D.
      • Murphy S.A.
      • et al.
      Evolocumab and clinical outcomes in patients with cardiovascular disease.
      The results were consistent in the subgroup of 1505 patients with LEAD alone. Further results are awaited.

      4.2.3 Antithrombotic drugs

      Antiplatelet agents are used for secondary prevention of CV events in patients with symptomatic PADs. The evidence is mostly available in patients with LEAD and cerebrovascular disease (see chapter 5).

      4.2.4 Antihypertensive drugs

      Lowering systolic blood pressure (SBP) reduces CV events.
      • Staessen J.A.
      • Thijs L.
      • Gasowski J.
      • Cells H.
      • Fagard R.H.
      Treatment of isolated systolic hypertension in the elderly: further evidence from the systolic hypertension in Europe (Syst-Eur) trial.
      According to the current ESC/European Society of Hypertension guidelines,
      • Mancia G.
      • Fagard R.
      • Narkiewicz K.
      • Redon J.
      • Zanchetti A.
      • Bohm M.
      • et al.
      2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
      a target BP <140/90 mmHg is recommended except in patients with diabetes, for whom a diastolic blood pressure ≤85 mmHg is considered safe. In patients with LEAD, this is mainly based on data from the INternational VErapamil-SR/Trandolapril (INVEST) study.
      • Bavry A.A.
      • Anderson R.D.
      • Gong Y.
      • Denardo S.J.
      • Cooper-Dehoff R.M.
      • Handberg E.M.
      • et al.
      Outcomes among hypertensive patients with concomitant peripheral and coronary artery disease: findings from the INternational VErapamil-SR/Trandolapril STudy.
      Caution should be exercised to avoid an SBP decrease below 110–120 mmHg, since a J-shape relationship between SBP and CV events has been reported in that trial in LEAD patients.
      • Bavry A.A.
      • Anderson R.D.
      • Gong Y.
      • Denardo S.J.
      • Cooper-Dehoff R.M.
      • Handberg E.M.
      • et al.
      Outcomes among hypertensive patients with concomitant peripheral and coronary artery disease: findings from the INternational VErapamil-SR/Trandolapril STudy.
      In old and frail patients, these levels should be achieved only if well tolerated, without orthostatic hypotension.
      • Wright Jr., J.T.
      • Williamson J.D.
      • Whelton P.K.
      • Snyder J.K.
      • Sink K.M.
      • Rocco M.V.
      • et al.
      A randomized trial of intensive versus standard blood-pressure control.
      • Cushman W.C.
      • Whelton P.K.
      • Fine L.J.
      • Wright Jr., J.T.
      • Reboussin D.M.
      • Johnson K.C.
      • et al.
      SPRINT trial results: latest news in hypertension management.
      In patients with PADs, an appropriate lifestyle and salt intake (<5–6 g/day) are recommended.
      • World Health Organization
      Guideline: sodium intake for adults and children.
      Diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are all suitable for antihypertensive treatment, as monotherapy or in different combinations. In the INVEST study, no difference in CV outcomes was found between the verapamil plus trandolapril strategy vs. the atenolol plus hydrochlorothiazide strategy.
      • Bavry A.A.
      • Anderson R.D.
      • Gong Y.
      • Denardo S.J.
      • Cooper-Dehoff R.M.
      • Handberg E.M.
      • et al.
      Outcomes among hypertensive patients with concomitant peripheral and coronary artery disease: findings from the INternational VErapamil-SR/Trandolapril STudy.
      Some classes may be preferred according to comorbidities.
      • Mancia G.
      • Fagard R.
      • Narkiewicz K.
      • Redon J.
      • Zanchetti A.
      • Bohm M.
      • et al.
      2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).
      The Heart Outcomes Prevention Trial (HOPE) and the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) have shown that ACEIs and ARBs significantly reduce CV events in patients with PADs.
      • Yusuf S.
      • Sleight P.
      • Pogue J.
      • Bosch J.
      • Davies R.
      • Dagenais G.
      Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.
      • Yusuf S.
      • Teo K.K.
      • Pogue J.
      • Dyal L.
      • Copland I.
      • Schumacher H.
      • et al.
      Telmisartan, ramipril, or both in patients at high risk for vascular events.
      According to these trials, ACEIs or ARBs are recommended for secondary prevention, even in patients with chronic limb-threatening ischaemia (CLTI). In this subgroup of patients, the use of ACEIs or ARBs is associated with decreased major adverse cardiovascular events (MACEs) and mortality without any effect on limb outcomes.
      • Armstrong E.J.
      • Chen D.C.
      • Singh G.D.
      • Amsterdam E.A.
      • Laird J.R.
      Angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use is associated with reduced major adverse cardiovascular events among patients with critical limb ischemia.
      Importantly, beta-blockers are not contraindicated in patients with LEAD, as they do not alter walking capacity in patients with mild to moderate LEAD.
      • Paravastu S.C.
      • Mendonca D.A.
      • Da Silva A.
      Beta blockers for peripheral arterial disease.
      In an observational study, patients with LEAD and prior MI and taking beta-blockers had a significant 53% coronary events risk decrease at 32 months.
      • Aronow W.S.
      • Ahn C.
      Effect of beta blockers on incidence of new coronary events in older persons with prior myocardial infarction and symptomatic peripheral arterial disease.
      Nevertheless, they should be carefully prescribed to patients with CLTI.
      Tabled 1Recommendations in patients with peripheral arterial diseases: best medical therapy
      • Law M.R.
      • Morris J.K.
      • Wald N.J.
      Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies.
      Table thumbnail fx11
      ACEIs = angiotensin-converting enzyme inhibitors; ARBs = angiotensin-receptor blockers; LDL-C = low-density lipoprotein cholesterol; PADs = peripheral arterial diseases.
      aClass of recommendation.
      bLevel of evidence.
      cCalcium channel blockers should be proposed in black individuals.
      dEvidence is not available for all sites. When evidence is available, recommendations specific for the vascular site are presented in corresponding sections.

      5. Antithrombotic drugs in PADs

      • Antiplatelet therapy is indicated in all patients with carotid artery stenosis irrespective of clinical symptoms and revascularization. Dual antiplatelet therapy (DAPT) should be given for at least 1 month after CAS.
      • Single antiplatelet therapy (SAPT) is indicated only if LEAD patients are symptomatic or have undergone revascularization. Clopidogrel is the preferred antiplatelet drug in LEAD patients.
      • Chronic anticoagulation therapy is given only if there is a concomitant indication and may be combined with SAPT when there is a recent revascularization procedure.
      Antiplatelet therapy is part of BMT for symptomatic PADs (see chapter 4). The specific issues about CAD and LEAD are addressed here. The question of DAPT after endovascular therapy in other territories as well as the sensitive issue of PADs patients requiring anticoagulation [e.g. with concomitant atrial fibrillation (AF)] are also addressed.

      5.1 Antithrombotic treatment in carotid artery disease

      5.1.1 Single antiplatelet therapy

      While the benefit of SAPT for preventing stroke in asymptomatic patients with carotid artery stenosis >50% is not evidenced through an RCT, lifelong low-dose aspirin should be part of BMT to reduce the risk of stroke and other CV events,
      Antithrombotic Trialists' Collaboration
      Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
      as these patients are also at twice the risk of MI.
      • Pickett C.A.
      • Jackson J.L.
      • Hemann B.A.
      • Atwood J.E.
      Carotid bruits as a prognostic indicator of cardiovascular death and myocardial infarction: a meta-analysis.
      In symptomatic extracranial carotid stenosis, antiplatelet monotherapy is recommended.
      Antithrombotic Trialists' Collaboration
      Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
      • Sacco R.L.
      • Diener H.C.
      • Yusuf S.
      • Cotton D.
      • Ounpuu S.
      • Lawton W.A.
      • et al.
      Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke.
      Clopidogrel (75 mg/day) is an alternative in patients with aspirin intolerance.
      • CAPRIE Steering Committee
      A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE).

      5.1.2 Dual antiplatelet therapy

      In the randomized Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial, asymptomatic CAD was an inclusion criteria in 7% of patients enrolled. No benefit was observed between DAPT vs. SAPT.
      • Bhatt D.L.
      • Flather M.D.
      • Hacke W.
      • Berger P.B.
      • Black H.R.
      • Boden W.E.
      • et al.
      Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial.
      The Clopidogrel and Aspirin for the Reduction of Emboli in Symptomatic carotid Stenosis (CARESS) study, conducted in 108 patients, demonstrated that DAPT vs. aspirin reduced silent cerebral micro-emboli by 37% after 7 days.
      • Markus H.S.
      • Droste D.W.
      • Kaps M.
      • Larrue V.
      • Lees K.R.
      • Siebler M.
      • et al.
      Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using Doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial.
      No life-threatening intracranial or major bleeding was observed, but the sample size was small. For these reasons, DAPT may be considered within 24 h of a minor ischaemic stroke or transient ischaemic attack (TIA) and may be continued for 1 month in patients treated conservatively.
      • Wang Y.
      • Wang Y.
      • Zhao X.
      • Liu L.
      • Wang D.
      • Wang C.
      • et al.
      Clopidogrel with aspirin in acute minor stroke or transient ischemic attack.
      DAPT is recommended in patients undergoing CAS. Two small RCTs comparing aspirin alone with DAPT for CAS were terminated prematurely due to high rates of stent thrombosis and neurological events in the aspirin-alone group.
      • Dalainas I.
      • Nano G.
      • Bianchi P.
      • Stegher S.
      • Malacrida G.
      • Tealdi D.G.
      Dual antiplatelet regime versus acetyl-acetic acid for carotid artery stenting.
      • 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.
      These data were obtained at 30 days. Most events were procedure related. The optimal duration of DAPT following CAS is unknown. Recent studies showing late brain lesions on diffusion-weighted MRI after CAS question whether DAPT beyond the first month may be required.
      • 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.
      However, potential risks include haemorrhagic transformation in patients with recent stroke and intracranial bleeding in patients at risk of reperfusion injury following revascularization. DAPT may be prolonged beyond 1 month after CAS in the presence of recent (<12 months) MI and low bleeding risk (Figure 1).
      • Udell J.A.
      • Bonaca M.P.
      • Collet J.P.
      • Lincoff A.M.
      • Kereiakes D.J.
      • Costa F.
      • et al.
      Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials.
      Figure 1
      Figure 1Management of antithrombotic treatment in patients with carotid artery stenosis.

      5.2 Antithrombotic therapy in lower extremity artery disease

      Antiplatelet agents are used in patients with LEAD to prevent limb-related and general CV events. A number of antiplatelet strategies are available, but their specific indications remain unclear.
      • Schmit K.
      • Dolor R.J.
      • Jones W.S.
      • Vemulapalli S.
      • Hasselblad V.
      • Subherwal S.
      • et al.
      Comparative effectiveness review of antiplatelet agents in peripheral artery disease.
      One study compared clopidogrel with aspirin
      • CAPRIE Steering Committee
      A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE).
      and two studies compared clopidogrel plus aspirin to aspirin alone.
      • Belch J.J.
      • Dormandy J.
      • Biasi G.M.
      • Cairols M.
      • Diehm C.
      • Eikelboom B.
      • et al.
      Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial.
      • Cacoub P.P.
      • Bhatt D.L.
      • Steg P.G.
      • Topol E.J.
      • Creager M.A.
      Patients with peripheral arterial disease in the CHARISMA trial.
      No specific trial addressed the role of antiplatelet agents in the full spectrum of LEAD (asymptomatic, IC and CLTI). Also, the Task Force is aware of the premature halting of the COMPASS trial for ‘overwhelming’ efficacy. The trial compared rivaroxaban monotherapy (5 mg twice a day) with dual therapy (aspirin plus rivaroxaban 2.5 mg twice a day) and with aspirin monotherapy in 27 402 patients with CAD or LEAD. As the data were neither presented nor published at the time of guideline printing, the Task Force was unable to address these results and their potential clinical consequences. Hence the Task Force will consider the results when they become available, as well as the option for an update if necessary.

      5.2.1 Single antiplatelet therapy

      Two trials, one in a general population (with ABI <0.95)
      • Fowkes F.G.
      • Price J.F.
      • Stewart M.C.
      • Butcher I.
      • Leng G.C.
      • Pell A.C.
      • et al.
      Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial.
      and another in diabetic patients (with ABI <1.0),
      • Belch J.
      • MacCuish A.
      • Campbell I.
      • Cobbe S.
      • Taylor R.
      • Prescott R.
      • et al.
      The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease.
       found no benefit from aspirin in subclinical LEAD.
      In symptomatic LEAD, the strongest evidence in favour of aspirin to protect against MACE (combining non-fatal MI and stroke with CV death) comes from the Antithrombotic Trialists Collaboration.
      Antithrombotic Trialists' Collaboration
      Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
      In 6200 patients with IC, aspirin significantly reduced MACE vs. controls (6.4 vs. 7.9%). Another meta-analysis of RCTs comparing aspirin to placebo in patients with LEAD (symptomatic or asymptomatic) showed a non-significant reduction in MACE {relative risk [RR] 0.75 [95% confidence interval (CI) 0.48–1.18]}.
      • Berger J.S.
      • Krantz M.J.
      • Kittelson J.M.
      • Hiatt W.R.
      Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease: a meta-analysis of randomized trials.
      No significant benefit was found within the individual components except for a reduction in non-fatal stroke [RR 0.64 (95% CI 0.42–0.99)].
      • Berger J.S.
      • Krantz M.J.
      • Kittelson J.M.
      • Hiatt W.R.
      Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease: a meta-analysis of randomized trials.
      In a post hoc analysis of the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) trial, at 3 years, clopidogrel was superior to aspirin in the subgroup of patients with clinical LEAD (n = 6452), with significant reductions in CV mortality [hazard ratio (HR) 0.76 (95% CI 0.64–0.91)] and MACE [HR 0.78 (95% CI 0.65–0.93)], with similar benefit in the subgroup of LEAD patients with diabetes.
      • CAPRIE Steering Committee
      A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE).
      In the randomized Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease (EUCLID) trial, ticagrelor was compared to clopidogrel in 13 885 patients ≥50 years of age with symptomatic LEAD.
      • Hiatt W.R.
      • Fowkes F.G.
      • Heizer G.
      • Berger J.S.
      • Baumgartner I.
      • Held P.
      • et al.
      Ticagrelor versus clopidogrel in symptomatic peripheral artery disease.
      The trial failed to show any difference regarding MACE [HR 1.02 (95% CI 0.92–1.13)] or major bleeding [HR 1.10 (95% CI 0.84–1.43)].

      5.2.2 Dual and triple antiplatelet therapy

      So far, data proving the superiority of DAPT (with clopidogrel) over aspirin alone to reduce CV events in patients with LEAD are lacking.
      • Schmit K.
      • Dolor R.J.
      • Jones W.S.
      • Vemulapalli S.
      • Hasselblad V.
      • Subherwal S.
      • et al.
      Comparative effectiveness review of antiplatelet agents in peripheral artery disease.
      In the subgroup of patients with LEAD enrolled in the CHARISMA trial (n = 3906), DAPT led to a reduction in MI [HR 0.63 (95% CI 0.42–0.95)], with a neutral effect on all the other vascular events, at the cost of increased severe, fatal or moderate bleeding [HR 1.99 (95% CI 1.69–2.34)].
      • Cacoub P.P.
      • Bhatt D.L.
      • Steg P.G.
      • Topol E.J.
      • Creager M.A.
      Patients with peripheral arterial disease in the CHARISMA trial.
      Because of the post hoc nature of this analysis and the negative results of the overall trial, these findings need confirmation.
      Vorapaxar, a protease-activated receptor-1 inhibitor, was tested vs. placebo on top of standard antiplatelet therapy in secondary prevention in patients with clinical LEAD (n = 3787).
      • Bonaca M.P.
      • Scirica B.M.
      • Creager M.A.
      • Olin J.
      • Bounameaux H.
      • Dellborg M.
      • et al.
      Vorapaxar in patients with peripheral artery disease: results from TRA2°P-TIMI 50.
      Vorapaxar did not reduce the risk of MACE [HR 0.94 (95% CI 0.78–1.14)] but significantly reduced the risk of acute limb ischaemia [HR 0.58 (95% CI 0.39–0.86)] and peripheral revascularization [HR 0.84 (95% CI 0.73–0.97)].
      • Bonaca M.P.
      • Scirica B.M.
      • Creager M.A.
      • Olin J.
      • Bounameaux H.
      • Dellborg M.
      • et al.
      Vorapaxar in patients with peripheral artery disease: results from TRA2°P-TIMI 50.
      This benefit was observed irrespective of the underlying mechanism of acute limb ischaemia, including surgical graft thrombosis and native vessel thrombosis.
      • Bonaca M.P.
      • Gutierrez J.A.
      • Creager M.A.
      • Scirica B.M.
      • Olin J.
      • Murphy S.A.
      • et al.
      Acute limb ischemia and outcomes with vorapaxar in patients with peripheral artery disease: results from the Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis in Myocardial Infarction 50 (TRA2°P-TIMI 50).
      These beneficial effects were counterbalanced by an increased risk of bleeding [HR 1.62 (95% CI 1.21–2.18)].

      5.2.3 Antithrombotic therapy after lower-extremity bypass grafting

      Antiplatelet agents are mostly used after peripheral percutaneous revascularization, while warfarin has a small role (Figure 2). No conclusive data are yet available for direct oral thrombin and factor Xa inhibitors.
      • Bedenis R.
      • Lethaby A.
      • Maxwell H.
      • Acosta S.
      • Prins M.H.
      Antiplatelet agents for preventing thrombosis after peripheral arterial bypass surgery.
      Figure 2
      Figure 2Antiplatelet therapy in patients with lower extremity artery disease.

      5.2.3.1 Aspirin vs. placebo

      In a meta-analysis of 952 patients, graft patency was significantly improved with aspirin (with or without dipyridamole) vs. placebo (HR 0.42, P = 0.01).
      • Bedenis R.
      • Lethaby A.
      • Maxwell H.
      • Acosta S.
      • Prins M.H.
      Antiplatelet agents for preventing thrombosis after peripheral arterial bypass surgery.
      Notably, at any of the time points, this effect was not observed for venous grafts alone but for prosthetic grafts (at 12 months: OR 0.19, P < 0.00001). Amputation, survival and bleeding rates were similar.

      5.2.3.2 Aspirin vs. oral anticoagulation

      In the Dutch Bypass Oral Anticoagulants or Aspirin Study, no difference in graft patency was found between aspirin (or aspirin/dipyridamole) and vitamin K antagonist (VKA) over 2 years of follow-up [HR 0.64 (95% CI 0.25–1.63)].
      Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral Anticoagulants or Aspirin Study): a randomised trial.
      There was no difference in mortality [OR 1.02 (95% CI 0.83–1.26)] or amputation [OR 0.99 (95% CI 0.75–1.30)]. Major bleeding risk doubled with VKA [with high target international normalized ratios (INRs) > 3].
      Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral Anticoagulants or Aspirin Study): a randomised trial.
      There were significantly fewer venous bypass occlusions under VKA vs. aspirin [HR 0.69 (95% CI 0.51–0.94)]. In another study, the addition of warfarin to aspirin failed to show any improvement in graft patency vs. aspirin alone, with a 2-fold increased risk of major bleeding.
      • Johnson W.C.
      • Williford W.O.
      Benefits, morbidity, and mortality associated with long-term administration of oral anticoagulant therapy to patients with peripheral arterial bypass procedures: a prospective randomized study.
      DAPT has been compared with VKA plus clopidogrel (n = 341) in femoro-popliteal bypass, with marginal benefit on graft failure, more bleeding and no effect on MACE.
      • Monaco M.
      • Di Tommaso L.
      • Pinna G.B.
      • Lillo S.
      • Schiavone V.
      • Stassano P.
      Combination therapy with warfarin plus clopidogrel improves outcomes in femoropopliteal bypass surgery patients.

      5.2.3.3 Aspirin vs. dual antiplatelet therapy

      Among the 851 patients with below-the-knee bypass grafting enrolled in the Clopidogrel and Acetylsalicylic Acid in Bypass Surgery for Peripheral Arterial disease (CASPAR) randomized controlled trial, no difference between aspirin plus placebo vs. aspirin plus clopidogrel was found regarding the occurrence of index graft occlusion or revascularization, above-ankle amputation of the affected limb or death [HR 0.98 (95% CI 0.78–1.23)].
      • Belch J.J.
      • Dormandy J.
      • Biasi G.M.
      • Cairols M.
      • Diehm C.
      • Eikelboom B.
      • et al.
      Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial.
      In the pre-specified subgroup of patients with a prosthetic graft, the primary efficacy endpoint was reduced in DAPT patients vs. aspirin alone [HR 0.65 (95% CI 0.45–0.95)] with a significant interaction according to the type of graft (venous vs. prosthetic). There was no statistically significant difference in the incidence of primary events when a venous graft was used [HR 1.25 (95% CI 0.94–1.67)]. Although total bleeding was more frequent on DAPT [HR 2.65 (95% CI 1.69–4.15)], there was no significant difference regarding severe or fatal bleeding (2.1 vs. 1.2%).

      5.2.4 Antithrombotic drugs after endovascular therapy for lower extremity artery disease

      DAPT is currently recommended for at least 1 month after intervention, irrespective of the stent type (bare metal vs. drug eluting). In the Zilver PTX randomized trial comparing provisional drug-eluting stents to bare-metal stents, DAPT was mandated for 2 months.
      • Dake M.D.
      • Ansel G.M.
      • Jaff M.R.
      • Ohki T.
      • Saxon R.R.
      • Smouse H.B.
      • et al.
      Durable clinical effectiveness with paclitaxel-eluting stents in the femoropopliteal artery: 5-year results of the Zilver PTX randomized trial.
      In the IN.PACT SFA trial, half of the patients were on DAPT at 1 year.
      • Laird J.R.
      • Schneider P.A.
      • Tepe G.
      • Brodmann M.
      • Zeller T.
      • Metzger C.
      • et al.
      Durability of treatment effect using a drug-coated balloon for femoropopliteal lesions: 24-month results of IN.PACT SFA.
      Stenting below-the-knee arteries is often followed by a longer period of DAPT, but no specific evidence is available. Anticoagulation has been prospectively tested after percutaneous infra-inguinal revascularization. Vascular patency was not improved, while bleeding was significantly increased.
      • Dagher N.N.
      • Modrall J.G.
      Pharmacotherapy before and after revascularization: anticoagulation, antiplatelet agents, and statins.

      5.2.5 Patients with lower extremity artery disease and concomitant coronary artery disease

      In patients with CAD, the coexistence of LEAD is associated with a worse prognosis irrespective of the clinical presentation. It has a direct impact on the duration and type of antiplatelet therapy regimen, in particular when there is a prior history of coronary stenting or acute coronary syndrome (ACS). The coexistence of LEAD in patients with CAD may be an argument for prolonged DAPT. The PROlonging Dual antiplatelet treatment after Grading stent-induced intimal hYperplasia (PRODIGY) trial tested DAPT duration after ACS. Prolonged (24 months) vs. short (6 months) DAPT conveyed a lower risk of the primary efficacy endpoint, a composite of death, MI or cerebrovascular accidents, in patients with LEAD [HR 0.54 (95% CI 0.31–0.95)] but not in those without [HR 1.28 (95% CI 0.92–1.77)]. A significant interaction (P = 0.01) suggests specific benefits only in patients with concomitant LEAD.
      • Franzone A.
      • Piccolo R.
      • Gargiulo G.
      • Ariotti S.
      • Marino M.
      • Santucci A.
      • et al.
      Prolonged vs short duration of dual antiplatelet therapy after percutaneous coronary intervention in patients with or without peripheral arterial disease: a subgroup analysis of the PRODIGY randomized clinical trial.
      In the Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial, the addition of ticagrelor 90 mg twice a day or 60 mg twice a day on top of low-dose aspirin in stable patients with prior MI (1–3 years) was investigated.
      • Bonaca M.P.
      • Bhatt D.L.
      • Cohen M.
      • Steg P.G.
      • Storey R.F.
      • Jensen E.C.
      • et al.
      Long-term use of ticagrelor in patients with prior myocardial infarction.
      Among patients with known LEAD (5% of the entire population), ticagrelor (pooled doses) reduced significantly the risk of major adverse limb outcomes (acute limb ischaemia and peripheral revascularization) [HR 0.65 (95% CI 0.44–0.95)]. In addition, in patients with LEAD, ticagrelor showed the greatest benefit, with an absolute risk reduction (ARR) of 4.1% [number needed to treat (NNT) = 25] for MACE and an absolute excess of major bleeding of 0.12% [number needed to harm (NNH) = 834].
      • Bonaca M.P.
      • Bhatt D.L.
      • Storey R.F.
      • Steg P.G.
      • Cohen M.
      • Kuder J.
      • et al.
      Ticagrelor for prevention of ischemic events after myocardial infarction in patients with peripheral artery disease.
      Therefore, long-term ticagrelor on top of low-dose aspirin may be considered in LEAD patients with prior MI (<3 years).
      DAPT duration in these settings should follow the current guidelines.

      2017 Guidelines for DAPT (citation pending).

      In LEAD patients who underwent infra-inguinal percutaneous revascularization, DAPT may be prolonged beyond 1 month when there is a prior history (<1 year) of ACS and/or percutaneous coronary intervention (PCI) (Figure 2). Yearly reassessment of DAPT should be considered according to the patient's clinical status.

      5.3 Antithrombotic therapy in lower extremity artery disease patients requiring long-term oral anticoagulant

      AF is frequent in patients with LEAD, with a worse outcome as compared to those without AF (see section 12.3).
      • Kirchhof P.
      • Benussi S.
      • Kotecha D.
      • Ahlsson A.
      • Atar D.
      • Casadei B.
      • et al.
      2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.
      • Winkel T.A.
      • Hoeks S.E.
      • Schouten O.
      • Zeymer U.
      • Limbourg T.
      • Baumgartner I.
      • et al.
      Prognosis of atrial fibrillation in patients with symptomatic peripheral arterial disease: data from the REduction of Atherothrombosis for Continued Health (REACH) Registry.
      Although evidence is scarce to support a specific antithrombotic regimen in patients with LEAD and an indication for oral anticoagulation (OAC), the first step is to reassess the indication for OAC. OAC should be continued only if a compelling indication exists (e.g. paroxysmal, persistent or permanent AF with a Congestive heart failure, Hypertension, Age ≥75 (2 points), Diabetes mellitus, Stroke or TIA (2 points), Vascular disease, Age 65–74 years, Sex category (CHA2DS2-VASc) score ≥2; mechanical heart valve; recent or a history of recurrent deep venous thrombosis or pulmonary embolism). Importantly, LEAD accounts for 1 point in the CHA2DS2-VASC score and can shift the indication for OAC. A post hoc analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial reported a significant interaction for major and non-major clinically relevant bleeding in patients with LEAD (n = 839) treated with rivaroxaban vs. warfarin [HR 1.40 (95% CI 1.06–1.86)] compared to patients without LEAD [HR 1.03 (95% CI 0.95–1.11); interaction P = 0.037].
      • Jones W.S.
      • Hellkamp A.S.
      • Halperin J.
      • Piccini J.P.
      • Breithardt G.
      • Singer D.E.
      • et al.
      Efficacy and safety of rivaroxaban compared with warfarin in patients with peripheral artery disease and non-valvular atrial fibrillation: insights from ROCKET AF.
      Additional studies are needed.
      The duration of combined therapy should be as limited as possible (1 month), depending on the clinical indication and bleeding risk.

      2017 Guidelines for DAPT (citation pending).

      • Kirchhof P.
      • Benussi S.
      • Kotecha D.
      • Ahlsson A.
      • Atar D.
      • Casadei B.
      • et al.
      2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.
      The addition of an antiplatelet treatment may depend on concomitant CAD and the need for LEAD endovascular revascularization. With the exception of below-the-knee stenting or complex lesions at very high risk of thrombosis, triple therapy (i.e. aspirin, clopidogrel and an anticoagulant) is discouraged in this setting. The proposed treatment algorithm taking into account the management strategy and bleeding risk is shown in Figure 3. Gastric protection with a proton pump inhibitor is recommended and the dose intensity of OAC should be carefully monitored with a target INR of 2.0–2.5 in patients treated with VKA, with the exception of individuals with mechanical prosthetic valves in the mitral position. In patients treated with non-vitamin K oral anticoagulants (NOACs), the lowest dose in approval studies for stroke prevention should be applied when combined with antiplatelet therapy.
      • Kirchhof P.
      • Benussi S.
      • Kotecha D.
      • Ahlsson A.
      • Atar D.
      • Casadei B.
      • et al.
      2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.
      • Heidbuchel H.
      • Verhamme P.
      • Alings M.
      • Antz M.
      • Diener H.C.
      • Hacke W.
      • et al.
      Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation.
      Figure 3
      Figure 3Antithrombotic therapy in patients with LEAD requiring oral anticoagulation.

      5.4 Antithrombotic therapy after endovascular therapy in other territories

      See Web addenda 5.4.
      Tabled 1Recommendations on antithrombotic therapy in patients with peripheral arterial diseases
      • Baigent C.
      • Blackwell L.
      • Collins R.
      • Emberson J.
      • Godwin J.
      • Peto R.
      • et al.
      Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials.
      • Donaldson D.R.
      • Kester R.C.
      • Rajah S.M.
      • Hall T.J.
      • Sreeharan N.
      • Crow M.J.
      The influence of platelet inhibition on the patency of femoro-popliteal Dacron bypass grafts.
      • McCollum C.
      • Alexander C.
      • Kenchington G.
      • Franks P.J.
      • Greenhalgh R.
      Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial.
      • Hart R.G.
      • Pearce L.A.
      • Aguilar M.I.
      Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation.
      • Lamberts M.
      • Lip G.Y.
      • Ruwald M.H.
      • Hansen M.L.
      • Ozcan C.
      • Kristensen S.L.
      • et al.
      Antithrombotic treatment in patients with heart failure and associated atrial fibrillation and vascular disease: a nationwide cohort study.
      Table thumbnail fx12
      AF = atrial fibrillation; CAS = carotid artery stenosis; CHA2DS2-VASc = Congestive heart failure, Hypertension, Age ≥75 (2 points), Diabetes mellitus, Stroke or TIA (2 points), Vascular disease, Age 65–74 years, Sex category; DAPT = dual antiplatelet therapy; LEAD = lower extremity artery disease; OAC = oral anticoagulation; PADs = peripheral arterial diseases; SAPT = single antiplatelet therapy.
      CHA2DS2-VASc score is calculated as follows: congestive heart failure history (1 point), hypertension (1 point), age >75 years (2 points), diabetes mellitus (1 point), stroke or TIA or arterial thromboembolic history (1 point), vascular disease history (1 point), age 65–74 years (1 point), sex category (1 point if female).
      aClass of recommendation.
      bLevel of evidence.
      cWith the exception of patients with an indication for long-term OAC.
      dWithout any other clinical cardiovascular condition requiring antiplatelet therapy (e.g. coronary artery disease or other multisite artery diseases).

      6. Extracranial carotid and vertebral artery disease

      • Of all strokes, 10–15% follow thromboembolism from a 50–99% internal carotid artery stenosis.
      • The majority of recently symptomatic patients will gain maximum benefit when carotid interventions are performed within 14 days of symptom onset.
      • Given the improved prognosis with BMT, the management of asymptomatic carotid disease remains controversial. However, some subgroups of patients may benefit from revascularization.
      • Predicting the magnitude of the perioperative risk of stroke can determine whether carotid endarterectomy or CAS is safer in individual patients, especially in the early time period after the onset of symptoms and in patients >70 years of age. After the perioperative period, late stroke rates after carotid endarterectomy and CAS are similar.
      • Vertebral artery stenoses are usually treated medically, unless recurrent symptoms persist despite BMT.

      6.1 Carotid artery disease

      6.1.1 Definition

      The different presentation modes of cerebrovascular events are detailed in Web Table 4.
      • Sacco R.L.
      • Kasner S.E.
      • Broderick J.P.
      • Caplan L.R.
      • Connors J.J.
      • Culebras A.
      • et al.
      An updated definition of stroke for the 21st century: a statement for healthcare professionals from the American Heart Association/American Stroke Association.
      This chapter primarily deals with stroke secondary to carotid and vertebral artery disease but not cardioembolism. Carotid artery stenosis refers to a ≥50% stenosis of the extracranial internal carotid artery (ICA), with stenosis severity estimated using the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method (Web Figure 1).
      • Donnan G.A.
      • Davis S.M.
      • Chambers B.R.
      • Gates P.C.
      Surgery for prevention of stroke.
      According to the definitions in major trials, carotid stenosis is defined as ‘symptomatic’ if associated with symptoms in the preceding 6 months and ‘asymptomatic’ if no prior symptoms can be identified or when symptoms occurred >6 months ago.

      6.1.2 Diagnosis

      6.1.2.1 Clinical evaluation

      The different presentation modes of cerebrovascular events are presented in the Web addenda 6.1.2.1.

      6.1.2.2 Imaging

      In patients with TIA/stroke, urgent imaging of the brain and supra-aortic vessels is mandatory. DUS is usually the first-line carotid imaging modality to assess extracranial ICA stenoses. It includes Doppler velocity measurements and ratios for accurate evaluation of stenosis severity. Multiple criteria should be used for reliable estimation of stenosis. Further details are presented in a recent consensus document.

      Sprynger M, RF, Moonen M, Aboyans V, Edvardsen T, Alcantara M, et al. EACVI recommendations on echovascular imaging assessment of arterial diseases: Partim I, 2017 [in preparation].

      Plaque morphological evaluation using MRI or DUS (echolucency, intraplaque haemorrhage, surface irregularity) may identify patients with asymptomatic stenoses at higher risk of ipsilateral ischaemic stroke. Other markers are silent infarction on CT/MRI and the detection of spontaneous embolization using transcranial Doppler monitoring.
      • Esposito-Bauer L.
      • Saam T.
      • Ghodrati I.
      • Pelisek J.
      • Heider P.
      • Bauer M.
      • et al.
      MRI plaque imaging detects carotid plaques with a high risk for future cerebrovascular events in asymptomatic patients.
      • Gupta A.
      • Kesavabhotla K.
      • Baradaran H.
      • Kamel H.
      • Pandya A.
      • Giambrone A.E.
      • et al.
      Plaque echolucency and stroke risk in asymptomatic carotid stenosis: a systematic review and meta-analysis.
      • Naylor A.R.
      • Schroeder T.V.
      • Sillesen H.
      Clinical and imaging features associated with an increased risk of late stroke in patients with asymptomatic carotid disease.
      Combining DUS with transcranial Doppler and/or transcranial colour-coded DUS enables a more thorough assessment of intracranial stenoses and an evaluation of impaired cerebrovascular reserve.
      • Sloan M.A.
      • Alexandrov A.V.
      • Tegeler C.H.
      • Spencer M.P.
      • Caplan L.R.
      • Feldmann E.
      • et al.
      Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.
      The main advantage of CTA/MRA over DUS is their ability to image simultaneously from the aortic arch up to the intracranial circulation as well as brain parenchyma. While CT is more widely available and differentiates between ischaemic and haemorrhagic stroke, MRI is more sensitive in detecting brain ischaemia, especially in the early post-stroke period. CTA offers excellent sensitivity and specificity for detecting carotid stenosis.
      • 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.
      Severe calcification may overestimate stenosis severity. MRA does not visualize vascular calcification, an important issue should CAS be considered. In a meta-analysis, DUS, MRA and CTA were equivalent for detecting significant carotid stenosis.
      • 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.
      Intra-arterial DSA, necessary for guiding CAS but not carotid endarterectomy (CEA), is rarely required for diagnostic purposes and is used only in highly selected situations with discordant non-invasive imaging results or additional intracranial vascular disease. In a patient with recent TIA or stroke with 50–99% ICA stenosis, echocardiography and 24–72-h rhythm monitoring remains suitable to detect the potential source of cardioembolism, but this should not delay any carotid intervention.
      Tabled 1Recommendations for imaging of extracranial carotid arteries
      Table thumbnail fx13
      CAS = carotid artery stenting; CEA = carotid endarterectomy; CTA = computed tomography angiography; DUS = duplex ultrasound; MRA = magnetic resonance angiography.
      aClass of recommendation.
      bLevel of evidence.

      6.1.3 Treatment

      6.1.3.1 Medical therapy

      The medical management of patients with carotid disease is detailed in 4, 5.

      6.1.3.2 Open surgery

      6.1.3.2.1 Technical aspects

      Details about the technical performance of CEA (type of anaesthesia, patching, shunting and other details) are summarized in the Web addenda 6.1.3.2.1.

      6.1.3.2.2 Postoperative outcomes

      Several studies have identified prognostic factors and markers for an increased risk of stroke after CEA. See Web addenda 6.1.3.2.2.

      6.1.3.3 Endovascular techniques

      CAS is a potentially less invasive alternative to CEA, with a low risk of cranial nerve injury, wound complications and/or neck haematoma, but it is vulnerable to access complications. CAS offers advantages over CEA in the presence of a ‘hostile neck’ (previous radiation, recurrent stenosis), contralateral recurrent laryngeal nerve palsy or in the case of challenging surgical access [very high ICA lesions, proximal common carotid artery (CCA) lesions], though not necessarily with a lower risk of perioperative stroke. Patients at higher risk for suffering perioperative cardiac complications may benefit from CAS in order to reduce perioperative MI (more common after CEA).
      • Blackshear J.L.
      • Cutlip D.E.
      • Roubin G.S.
      • Hill M.D.
      • Leimgruber P.P.
      • Begg R.J.
      • et al.
      Myocardial infarction after carotid stenting and endarterectomy: results from the carotid revascularization endarterectomy versus stenting trial.
      In a subgroup analysis from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the 4-year mortality was significantly higher [HR 3.40 (95% CI 1.67–6.92)] in patients suffering a perioperative MI.
      • Blackshear J.L.
      • Cutlip D.E.
      • Roubin G.S.
      • Hill M.D.
      • Leimgruber P.P.
      • Begg R.J.
      • et al.
      Myocardial infarction after carotid stenting and endarterectomy: results from the carotid revascularization endarterectomy versus stenting trial.

      6.1.3.3.1 Carotid stenting: technical aspects

      6.1.3.3.1.1 Criteria associated with increased difficulty for carotid artery stenting

      6.1.3.3.1.2 Embolic protection devices

      The rationale for cerebral protection devices is supported by the presence of embolic material in distal filters,
      • Giannakopoulos T.G.
      • Moulakakis K.
      • Sfyroeras G.S.
      • Avgerinos E.D.
      • Antonopoulos C.N.
      • Kakisis J.D.
      • et al.
      Association between plaque echogenicity and embolic material captured in filter during protected carotid angioplasty and stenting.
      but their use remains controversial. Using diffusion-weighted MRI, studies have reported lower rates of cerebral embolization with a proximal embolus protection device (EPD), but none was powered to address clinical outcomes.
      • Akkaya E.
      • Vuruskan E.
      • Gul Z.B.
      • Yildirim A.
      • Pusuroglu H.
      • Surgit O.
      • et al.
      Cerebral microemboli and neurocognitive change after carotid artery stenting with different embolic protection devices.
      • Bijuklic K.
      • Wandler A.
      • Hazizi F.
      • Schofer J.
      The PROFI study (Prevention of Cerebral Embolization by Proximal Balloon Occlusion Compared to Filter Protection During Carotid Artery Stenting): a prospective randomized trial.
      • Cano M.N.
      • Kambara A.M.
      • de Cano S.J.
      • Pezzi Portela L.A.
      • Paes A.T.
      • Costa Jr., J.R.
      • et al.
      Randomized comparison of distal and proximal cerebral protection during carotid artery stenting.
      • Montorsi P.
      • Caputi L.
      • Galli S.
      • Ciceri E.
      • Ballerini G.
      • Agrifoglio M.
      • et al.
      Microembolization during carotid artery stenting in patients with high-risk, lipid-rich plaque. A randomized trial of proximal versus distal cerebral protection.
      • Stabile E.
      • Esposito G.
      Operator's experience is the most efficient embolic protection device for carotid artery stenting.
      A meta-analysis of 24 studies observed that EPD use was associated with a lower risk of perioperative stroke (RR 0.59; P < 0.001).
      • Garg N.
      • Karagiorgos N.
      • Pisimisis G.T.
      • Sohal D.P.
      • Longo G.M.
      • Johanning J.M.
      • et al.
      Cerebral protection devices reduce periprocedural strokes during carotid angioplasty and stenting: a systematic review of the current literature.
      A pooled analysis of RCTs also reported significantly lower rates of perioperative stroke/death (RR 0.57), favouring EPD.
      • Touze E.
      • Trinquart L.
      • Chatellier G.
      • Mas J.L.
      Systematic review of the perioperative risks of stroke or death after carotid angioplasty and stenting.
      The benefit of EPDs was also evident in a prospective registry of 1455 patients: in those treated with EPD, in-hospital death/stroke rates were at 2.1% vs. 4.9% in patients treated without EPD (P = 0.004).
      • Zahn R.
      • Ischinger T.
      • Hochadel M.
      • Zeymer U.
      • Schmalz W.
      • Treese N.
      • et al.
      Carotid artery stenting in octogenarians: results from the ALKK Carotid Artery Stent (CAS) Registry.
      The best results within RCTs were seen in the CREST and the Asymptomatic Carotid Trial (ACT-1), where cerebral protection was mandatory and CAS practitioners were trained in its use.
      • 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.
      In contrast, the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial observed lower ipsilateral stroke rates in CAS patients without EPD (6.2%) vs. with EPD (8.3%).
      • Jansen O.
      • Fiehler J.
      • Hartmann M.
      • Bruckmann H.
      Protection or nonprotection in carotid stent angioplasty: the influence of interventional techniques on outcome data from the SPACE Trial.
      Given the lack of high-quality data, the revised recommendation in these guidelines is based on a broad consensus that protection devices should be considered when performing CAS.
      Tabled 1Recommendation on the use of embolic protection device during carotid stenting
      Table thumbnail fx14
      aClass of recommendation.
      bLevel of evidence.

      6.1.3.3.2 Carotid artery stenting: operator experience and outcome

      Evidence suggests that experience plays a role in CAS outcomes.
      • Gray W.A.
      • Rosenfield K.A.
      • Jaff M.R.
      • Chaturvedi S.
      • Peng L.
      • Verta P.
      Influence of site and operator characteristics on carotid artery stent outcomes: analysis of the CAPTURE 2 (Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events) clinical study.
      • Nallamothu B.K.
      • Gurm H.S.
      • Ting H.H.
      • Goodney P.P.
      • Rogers M.A.
      • Curtis J.P.
      • et al.
      Operator experience and carotid stenting outcomes in Medicare beneficiaries.
      See Web addenda 6.1.3.3.2.

      6.1.4 Management of carotid artery disease

      6.1.4.1 Asymptomatic carotid artery disease

      6.1.4.1.1 Open surgery vs. medical therapy

      The Asymptomatic Carotid Atherosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial (ACST-1) compared CEA with medical therapy in asymptomatic patients with 60–99% carotid stenosis.
      Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
      • 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.
      • Halliday A.
      • Mansfield A.
      • Marro J.
      • Peto C.
      • Peto R.
      • Potter J.
      • et al.
      Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
      In ACAS, 5-year rates of ipsilateral stroke/death under CEA vs. medical therapy were 5.1% vs. 11.0%, respectively (P = 0.0001, NNT = 18). The 10-year risk of ‘any’ stroke rates were 13.4% vs. 17.9%, respectively (P = 0.009, NNT = 22). ACST-1 reported 5-year rates of any stroke of 6.4% vs. 11.8%, respectively (P < 0.0001, NNT = 19). Fatal/disabling stroke rates were 3.5% vs. 6.1%, respectively (P = 0.004, NNT = 38). In a combined analysis of both trials, CEA conferred less benefit in women at 5 years.
      • Rothwell P.M.
      • Eliasziw M.
      • Gutnikov S.A.
      • Warlow C.P.
      • Barnett H.J.
      Sex difference in the effect of time from symptoms to surgery on benefit from carotid endarterectomy for transient ischemic attack and nondisabling stroke.
      At 10 years, however, ACST-1
      • 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.
      reported that females gained a small but significant benefit following CEA (ARR 5.8%, P = 0.05). However, both trials are now rather dated. In a meta-analysis of 41 studies, the rate of ipsilateral stroke was 2.3/100 person-years in studies completing recruitment before 2000, compared with 1.0/100 person-years during the 2000–2010 period (P < 0.001).
      • Hadar N.
      • Raman G.
      • Moorthy D.
      • O'Donnell T.F.
      • Thaler D.E.
      • Feldmann E.
      • et al.
      Asymptomatic carotid artery stenosis treated with medical therapy alone: temporal trends and implications for risk assessment and the design of future studies.
      A 60–70% decline in annual stroke rates was also observed in medically treated patients in both trials over the recruitment period from 1995 to 2010.
      Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
      • 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.
      • Halliday A.
      • Mansfield A.
      • Marro J.
      • Peto C.
      • Peto R.
      • Potter J.
      • et al.
      Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
      • Naylor A.R.
      • Gaines P.A.
      • Rothwell P.M.
      Who benefits most from intervention for asymptomatic carotid stenosis: patients or professionals?.
      Despite the small but significant benefit favouring CEA over medical therapy, the ARR in stroke was only 4.6% at 10 years, indicating that 95% of asymptomatic patients ultimately underwent unnecessary interventions.
      • Naylor A.R.
      • Schroeder T.V.
      • Sillesen H.
      Clinical and imaging features associated with an increased risk of late stroke in patients with asymptomatic carotid disease.
      • 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.
      There is a need to target revascularization in a subgroup of patients with clinical and/or imaging features that may make them higher risk for stroke on BMT
      • Naylor A.R.
      • Schroeder T.V.
      • Sillesen H.
      Clinical and imaging features associated with an increased risk of late stroke in patients with asymptomatic carotid disease.
      (Table 4). Pending the development of better algorithms for patient selection, the presence of one or more of these clinical or imaging features might be useful for selecting patients for revascularization.
      Table 4Features associated with increased risk of stroke in patients with asymptomatic carotid stenosis treated medically (for details see Web Table 5).
      Clinical
      Age is not a predictor of poorer outcome.
      • Contralateral TIA/stroke
        • Nicolaides A.N.
        • Kakkos S.K.
        • Griffin M.
        • Sabetai M.
        • Dhanjil S.
        • Tegos T.
        • et al.
        Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: results from the ACSRS study.
      Cerebral imaging
      • Ipsilateral silent infarction
        • Kakkos S.K.
        • Sabetai M.
        • Tegos T.
        • Stevens J.
        • Thomas D.
        • Griffin M.
        • et al.
        Silent embolic infarcts on computed tomography brain scans and risk of ipsilateral hemispheric events in patients with asymptomatic internal carotid artery stenosis.
      Ultrasound imaging
      • Stenosis progression (> 20%)
        • Kakkos S.K.
        • Nicolaides A.N.
        • Charalambous I.
        • Thomas D.
        • Giannopoulos A.
        • Naylor A.R.
        • et al.
        Predictors and clinical significance of progression or regression of asymptomatic carotid stenosis.
      • Spontaneous embolization on transcranial Doppler (HITS)
        • Markus H.S.
        • King A.
        • Shipley M.
        • Topakian R.
        • Cullinane M.
        • Reihill S.
        • et al.
        Asymptomatic embolisation for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): a prospective observational study.
      • Impaired cerebral vascular reserve
        • King A.
        • Serena J.
        • Bornstein N.M.
        • Markus H.S.
        Does impaired cerebrovascular reactivity predict stroke risk in asymptomatic carotid stenosis? A prospective substudy of the asymptomatic carotid emboli study.
      • Large plaques
        More than 40 mm2 on digital analysis.
        • Nicolaides A.N.
        • Kakkos S.K.
        • Kyriacou E.
        • Griffin M.
        • Sabetai M.
        • Thomas D.J.
        • et al.
        Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification.
      • Echolucent plaques
        • Gupta A.
        • Kesavabhotla K.
        • Baradaran H.
        • Kamel H.
        • Pandya A.
        • Giambrone A.E.
        • et al.
        Plaque echolucency and stroke risk in asymptomatic carotid stenosis: a systematic review and meta-analysis.
      • Increased juxta-luminal black (hypoechogenic) area
        • Kakkos S.K.
        • Griffin M.B.
        • Nicolaides A.N.
        • Kyriacou E.
        • Sabetai M.M.
        • Tegos T.
        • et al.
        The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke.
      MRA
      • Intraplaque haemorrhage
        • Gupta A.
        • Baradaran H.
        • Schweitzer A.D.
        • Kamel H.
        • Pandya A.
        • Delgado D.
        • et al.
        Carotid plaque MRI and stroke risk: a systematic review and meta-analysis.
      • Lipid-rich necrotic core
      HITS = high intensity transient signal; MRA = magnetic resonance angiography; TIA = transient ischaemic attack.
      a Age is not a predictor of poorer outcome.
      b More than 40 mm2 on digital analysis.
      Importantly, ACST found no evidence that age >75 years at baseline was associated with any ipsilateral stroke reduction at 5 or 10 years. Additionally, the stenosis severity cannot be a criterion for stratifying late stroke risk. In a meta-analysis of 41 studies, ipsilateral stroke in patients with 50–69% and 70–99% stenosis were at 1.9 and 2.1/100 person-years, respectively (P value).
      • Hadar N.
      • Raman G.
      • Moorthy D.
      • O'Donnell T.F.
      • Thaler D.E.
      • Feldmann E.
      • et al.
      Asymptomatic carotid artery stenosis treated with medical therapy alone: temporal trends and implications for risk assessment and the design of future studies.
      Neither the ACAS nor ACST found any evidence that stenosis severity or contralateral occlusion increased late stroke risk.
      Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
      • 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.
      • Baker W.H.
      • Howard V.J.
      • Howard G.
      • Toole J.F.
      Effect of contralateral occlusion on long-term efficacy of endarterectomy in the Asymptomatic Carotid Atherosclerosis Study (ACAS). ACAS Investigators.

      6.1.4.1.2 Carotid revascularization: surgery vs. stenting

      Five RCTs compared CEA with CAS in ‘average risk for CEA’ asymptomatic patients (Web Table 6), while SPACE-2 also included a third limb for BMT. The two biggest RCTs (CREST and ACT-1) requested exclusively experienced interventionists. In ACT-1, the 2.9% rate of death/stroke after CAS fell within the 3% accepted risk. Because of the learning curve associated with CAS, as well as it being performed in small numbers by multiple specialties,
      • Hawkins B.M.
      • Kennedy K.F.
      • Aronow H.D.
      • Nguyen L.L.
      • White C.J.
      • Rosenfield K.
      • et al.
      Hospital variation in carotid stenting outcomes.
      there are concerns as to whether the death/stroke rates reported for CAS in these trials can be replicated in ‘real-world’ practice. While some national CAS registries have published death/stroke rates within 3%,
      • Kallmayer M.A.
      • Tsantilas P.
      • Knappich C.
      • Haller B.
      • Storck M.
      • Stadlbauer T.
      • et al.
      Patient characteristics and outcomes of carotid endarterectomy and carotid artery stenting: analysis of the German mandatory national quality assurance registry – 2003 to 2014.
      • Werner N.
      • Zeymer U.
      • Hochadel M.
      • Hauptmann K.E.
      • Jung J.
      • Janicke I.
      • et al.
      Fifteen-year experience with carotid artery stenting (from the carotid artery stenting-registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte).
      others have reported wide variations in practice. In a review of 19 381 CAS procedures in a registry, there was a 4-fold variation regarding in-hospital death/stroke despite adjusting for case mix.
      • Hawkins B.M.
      • Kennedy K.F.
      • Aronow H.D.
      • Nguyen L.L.
      • White C.J.
      • Rosenfield K.
      • et al.
      Hospital variation in carotid stenting outcomes.
      A systematic review in large administrative dataset registries (>1.5 million procedures) suggested that 40% of registries reported death/stroke rates after CAS >3% in asymptomatic patients, while 14% reported death/stroke rates >5%.
      • Paraskevas K.I.
      • Kalmykov E.L.
      • Naylor A.R.
      Stroke/death rates following carotid artery stenting and carotid endarterectomy in contemporary administrative dataset registries: a systematic review.
      In some large registries the median annual number of CAS procedures in asymptomatic patients may only be one or two,
      • Choi J.C.
      • Johnston S.C.
      • Kim A.S.
      Early outcomes after carotid artery stenting compared with endarterectomy for asymptomatic carotid stenosis.
      which is known to be associated with higher rates of perioperative stroke/death.
      • Dua A.
      • Romanelli M.
      • Upchurch Jr., G.R.
      • Pan J.
      • Hood D.
      • Hodgson K.J.
      • et al.
      Predictors of poor outcome after carotid intervention.
      The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial randomized symptomatic and asymptomatic patients deemed ‘high risk for surgery’ to either CEA or CAS (using EPDs routinely).
      • Yadav J.S.
      • Wholey M.H.
      • Kuntz R.E.
      • Fayad P.
      • Katzen B.T.
      • Mishkel G.J.
      • et al.
      Protected carotid-artery stenting versus endarterectomy in high-risk patients.
      High surgical risk was defined as clinically significant cardiac disease, severe pulmonary disease, contralateral ICA occlusion, contralateral recurrent laryngeal nerve palsy, previous radical neck surgery or radiotherapy, recurrent stenosis after CEA and age >80 years. The primary endpoint (30-day death/stroke/MI and/or death or ipsilateral stroke between 31 days and 1 year) occurred in 12.2% of CAS patients and 20.1% of CEA patients (P = 0.053). At 3 years, major ipsilateral stroke (CAS 1.3% vs. CEA 3.3%), minor ipsilateral stroke (6.1% vs. 3.0%) and repeat revascularization (3.0% vs. 7.1%) were not statistically different.
      • 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.
      However, 71% of SAPPHIRE patients were asymptomatic, in whom the 30-day rate of death/stroke after CAS was 5.8% vs. 6.1% after CEA,
      • Yadav J.S.
      • Wholey M.H.
      • Kuntz R.E.
      • Fayad P.
      • Katzen B.T.
      • Mishkel G.J.
      • et al.
      Protected carotid-artery stenting versus endarterectomy in high-risk patients.
      both beyond the recommended 3%. If these procedural risk levels reflect contemporary practice, most ‘high-risk for surgery’ asymptomatic patients would be better treated medically.
      Tabled 1Recommendations for management of asymptomatic carotid artery disease
      • Silver F.L.
      • Mackey A.
      • Clark W.M.
      • Brooks W.
      • Timaran C.H.
      • Chiu D.
      • et al.
      Safety of stenting and endarterectomy by symptomatic status in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).
      Table thumbnail fx15
      BP = blood pressure; CAS = carotid artery stenting; CEA = carotid endarterectomy.
      aClass of recommendation.
      bLevel of evidence.
      dAge >80 years, clinically significant cardiac disease, severe pulmonary disease, contralateral internal carotid artery occlusion, contralateral recurrent laryngeal nerve palsy, previous radical neck surgery or radiotherapy and recurrent stenosis after CEA.

      6.1.4.2 Symptomatic carotid artery disease

      6.1.4.2.1 Open surgery

      In a meta-analysis of all symptomatic patients randomized within NASCET and the European Carotid Surgery Trial (ECST), those with a NASCET 0–49% stenosis gained no benefit from surgery. CEA conferred a 7.8% ARR for stroke at 5 years in patients with 50–69% stenoses (NNT = 13). The maximum benefit was seen in patients with 70–99% ICA stenoses, where the ARR for stroke was 15.6% (NNT = 6).
      • Rothwell P.M.
      • Eliasziw M.
      • Gutnikov S.A.
      • Fox A.J.
      • Taylor D.W.
      • Mayberg M.R.
      • et al.
      Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis.
      A number of clinical/imaging features are associated with an increased rate of late stroke in symptomatic patients with 50–99% stenoses if treated medically: increasing age (especially >75 years), symptoms within 14 days, male sex, hemispheric (vs. retinal) symptoms, cortical (vs. lacunar) stroke, increasing number of medical comorbidities, irregular stenoses, increasing stenosis severity, contralateral occlusion, tandem intracranial stenoses and a failure to recruit intracranial collaterals.
      • Naylor A.R.
      • Sillesen H.
      • Schroeder T.V.
      Clinical and imaging features associated with an increased risk of early and late stroke in patients with symptomatic carotid disease.
      A meta-analysis from ECST and NASCET showed that when CEA was performed within 14 days in patients with 50–69% stenoses, the ARR for stroke at 5 years was 14.8% (NNT = 7). The ARR declined to 3.3% when the delay was 2–4 weeks (NNT = 30) and 2.5% when the delay was 4–12 weeks (NNT = 40). Beyond 12 weeks, no strokes were prevented by CEA. In patients with 70–99% stenoses who underwent CEA within 14 days, the ARR for stroke at 5 years was 23.0% (NNT = 4), falling to 15.9% where delays were 2–4 weeks (NNT = 6) and 7.9% for delays of 4–12 weeks (NNT = 13). When performed beyond 12 weeks, the ARR was 7.4% at 5 years (NNT = 14).
      • Rothwell P.M.
      • Eliasziw M.
      • Gutnikov S.A.
      • Warlow C.P.
      • Barnett H.J.
      Sex difference in the effect of time from symptoms to surgery on benefit from carotid endarterectomy for transient ischemic attack and nondisabling stroke.
      • Naylor A.R.
      • Sillesen H.
      • Schroeder T.V.
      Clinical and imaging features associated with an increased risk of early and late stroke in patients with symptomatic carotid disease.
      Women appeared to gain almost no benefit from CEA when performed beyond 4 weeks.
      • Rothwell P.M.
      • Eliasziw M.
      • Gutnikov S.A.
      • Warlow C.P.
      • Barnett H.J.
      Sex difference in the effect of time from symptoms to surgery on benefit from carotid endarterectomy for transient ischemic attack and nondisabling stroke.
      • Rothwell P.M.
      • Eliasziw M.
      • Gutnikov S.A.
      • Fox A.J.
      • Taylor D.W.
      • Mayberg M.R.
      • et al.
      Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis.
      • Naylor A.R.
      • Sillesen H.
      • Schroeder T.V.
      Clinical and imaging features associated with an increased risk of early and late stroke in patients with symptomatic carotid disease.
      The risk of stroke is high within the first days after TIA. The early risk of stroke in patients with 50–99% ICA stenoses ranged from 5 to 8% within 48 h after TIA, up to 17% by 72 h, 8–22% by 7 days and 11–25% at 14 days.
      • Naylor A.R.
      • Sillesen H.
      • Schroeder T.V.
      Clinical and imaging features associated with an increased risk of early and late stroke in patients with symptomatic carotid disease.
      There is controversy over whether CEA can be performed safely within the first 48 h after symptom onset. The Swedish Registry (n = 2596 CEAs) reported that when CEA was performed within the first 48 h, 11.5% died or suffered a stroke as compared with a procedural risk of <5% when done any time afterwards.
      • Stromberg S.
      • Gelin J.
      • Osterberg T.
      • Bergstrom G.M.
      • Karlstrom L.
      • Osterberg K.
      Very urgent carotid endarterectomy confers increased procedural risk.
      In contrast, the UK national audit (n = 23 235 CEAs) reported that when CEA was performed within 48 h, the rate of death/stroke was much lower than observed in Sweden (3.7%). Thereafter, procedural risks were <2%.
      • Loftus I.M.
      • Paraskevas K.I.
      • Johal A.
      • Waton S.
      • Heikkila K.
      • Naylor A.R.
      • et al.
      Delays to surgery and procedural risks following carotid endarterectomy in the UK National Vascular Registry.
      A similarly low risk of death/stroke (3.0%) was observed in Germany when CEA was performed in <48 h.
      • Tsantilas P.
      • Kuehnl A.
      • Konig T.
      • Breitkreuz T.
      • Kallmayer M.
      • Knappich C.
      • et al.
      Short time interval between neurologic event and carotid surgery is not associated with an increased procedural risk.
      These registries suggest that CEA can be performed safely in the first 7 days after TIA/minor stroke onset. However, not all patients will benefit from urgent revascularization. There may be an increased risk of haemorrhagic transformation within a recent area of infarction. Higher-risk patients include those with acute carotid occlusion or a persisting major neurological deficit, an area of middle cerebral artery infarction exceeding one-third, evidence of pre-existing parenchymal haemorrhage and evidence of impaired consciousness.
      A meta-analysis of five randomized trials has shown that emergency endovascular treatment of acute ischaemic stroke (mechanical thrombectomy and/or intra-arterial thrombolysis) was associated with 2.22 times greater odds of a better functional outcome compared with those randomized to medical management. Endovascular therapy was not associated with a modified risk of symptomatic intracerebral hemorrhage.
      • Bush C.K.
      • Kurimella D.
      • Cross L.J.
      • Conner K.R.
      • Martin-Schild S.
      • He J.
      • et al.
      Endovascular treatment with stent-retriever devices for acute ischemic stroke: a meta-analysis of randomized controlled trials.