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The Reply

  • Antonios Vitalis
    Affiliations
    Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK

    Institute of Cardiovascular Sciences, University of Birmingham, UK

    Department of Vascular Surgery, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, UK
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  • Alena Shantsila
    Affiliations
    Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK
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  • Gregory Y.H. Lip
    Correspondence
    Requests for reprints should be addressed to Gregory Y. H. Lip, MD, Price-Evans Professor of Cardiovascular Medicine, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK.
    Affiliations
    Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK

    Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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      We are grateful to Dr Jolobe for the interest in our paper.

      Vitalis A, Shantsila A, Proietti M, et al. Peripheral arterial disease in patients with atrial fibrillation: the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study [e-pub ahead of print]. Am J Med. Accessed January 18, 2021. doi:10.1016/j.amjmed.2020.08.026

      Carotid artery disease, peripheral arterial disease, and atrial fibrillation share common risk factors such as hypertension and diabetes;
      • Benjamin EJ
      • Blaha MJ
      • Chiuve SE
      • et al.
      Heart disease and stroke statistics—2017 update: a report from the American Heart Association.
      ,
      • Brandes A
      • Smit MD
      • Nguyen BO
      • Rienstra M
      • Van Gelder IC
      Risk factor management in atrial fibrillation.
      it is therefore expected that these conditions will often coexist. Indeed, significant carotid artery stenosis (>50%) has a prevalence of 12.4% in patients with atrial fibrillation
      • Noubiap JJ
      • Agbaedeng TA
      • Tochie JN
      • et al.
      Meta-analysis comparing the frequency of carotid artery stenosis in patients with atrial fibrillation and vice Versa.
      and 18.8% in patients with peripheral arterial disease
      • Razzouk L
      • Rockman CB
      • Patel MR
      • et al.
      Co-existence of vascular disease in different arterial beds: peripheral artery disease and carotid artery stenosis - data from Life Line Screening®.
      compared to a prevalence in the general population that ranges from 0.3% in those younger than the age of 50 years to 4.2% in those older than 80 years old.
      • de Weerd M
      • Greving JP
      • Hedblad B
      • et al.
      Prevalence of asymptomatic carotid artery stenosis in the general population.
      The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial was designed to compare treatment strategies for atrial fibrillation
      • Wyse DG
      • Waldo AL
      • DiMarco JP
      • et al.
      A comparison of rate control and rhythm control in patients with atrial Fibrillation.
      and data on coexisting carotid artery disease for enrolled patients with atrial fibrillation were beyond the scope of the study. We agree with Dr Jolobe that history of stroke observed in patients with atrial fibrillation and peripheral arterial disease could be to an extent augmented by coexisting carotid artery disease. Interestingly a recent meta-analysis has not demonstrated significant difference in prevalence of carotid stenosis between patients with atrial fibrillation with history of stroke/transient ischemic attack and those with no previous cerebrovascular event (13.5% vs 10.5%, P = .411).
      • Noubiap JJ
      • Agbaedeng TA
      • Tochie JN
      • et al.
      Meta-analysis comparing the frequency of carotid artery stenosis in patients with atrial fibrillation and vice Versa.
      The mechanisms of stroke in atrial fibrillation are multifactorial, with a complex interaction of cardiac causes, systemic risk factors and atherosclerosis of the great vessels, carotid arteries, and cerebral vessels, as well as optimal management.
      • Kamel H
      • Okin PM
      • Elkind MSV
      • Iadecola C
      Atrial fibrillation and mechanisms of stroke: time for a new model.
      ,
      • D'Souza A
      • Butcher KS
      • Buck BH
      The multiple causes of stroke in atrial fibrillation: thinking broadly.
      Indeed, our sensitivity analysis showed that only in the nonanticoagulated cohort of patients with atrial fibrillation, peripheral arterial disease was an independent predictor of ischemic stroke events. This emphasizes the important issue of the peripheral arterial disease being an independent stroke risk factor and requiring appropriate treatment to mitigate the risk.
      • Lip GYH
      • Banerjee A
      • Boriani G
      • et al.
      Antithrombotic therapy for atrial fibrillation: CHEST Guideline and expert panel report.
      We wish to reemphasize that aspirin is not recommended for stroke prevention in atrial fibrillation and that if used, it increases the risk of bleeding. In patients with coronary artery disease and atrial fibrillation, the concomitant use of aspirin, as part of a triple-therapy strategy for stent thrombosis prevention, is only recommended for 1 month. Long-term antithrombotic management of these patients, if they are stable from a coronary point of view, is based on anticoagulant monotherapy.

      Vitalis A, Shantsila A, Proietti M, et al. Peripheral arterial disease in patients with atrial fibrillation: the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study [e-pub ahead of print]. Am J Med. Accessed January 18, 2021. doi:10.1016/j.amjmed.2020.08.026

      The fact that significant carotid artery stenosis (>50%) is a risk factor for ischemic stroke is well recognized, although nonsignificant carotid artery plaques can be unstable because of the neovascularization (as we have previously shown)
      • Jaipersad AS
      • Shantsila A
      • Silverman S
      • Lip GYH
      • Shantsila E
      Evaluation of carotid plaque neovascularization using contrast ultrasound.
      and can be the source for recurrent stroke. Nonetheless, the data on management options for patients with atrial fibrillation and concomitant carotid artery disease are less robust. Some studies show that the recurrence of ischemic events in anticoagulated atrial fibrillation patients is higher in the presence of significant carotid artery stenosis,
      • Lehtola H
      • Airaksinen KEJ
      • Hartikainen P
      • et al.
      Stroke recurrence in patients with atrial fibrillation: concomitant carotid artery stenosis doubles the risk.
      whereas other prospective studies have not shown an increased stroke risk in anticoagulated patients with atrial fibrillation in the presence of either significant or nonsignificant carotid artery stenosis.
      • Becattini C
      • Dentali F
      • Camporese G
      • et al.
      Carotid atherosclerosis and risk for ischemic stroke in patients with atrial fibrillation on oral anticoagulant treatment.
      Further research is needed to clarify the prognostic impact of carotid disease and coexisting peripheral arterial disease in patients with atrial fibrillation and the optimal medical management of these patients. Current evidence to support routine screening to detect asymptomatic carotid disease is limited.
      • Naylor AR
      • Ricco JB
      • de Borst GJ
      • et al.
      Editor's Choice – management of atherosclerotic carotid and vertebral artery disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS).

      References

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