Thromb Haemost 2022; 122(02): 277-285
DOI: 10.1055/a-1541-3885
Stroke, Systemic or Venous Thromboembolism

Risk of Ischemic Stroke in Asymptomatic Atrial Fibrillation Incidentally Detected in Primary Care Compared with Other Clinical Presentations

1   Institute for Epidemiology, Statistics and Informatics GmbH, Frankfurt, Germany
1   Institute for Epidemiology, Statistics and Informatics GmbH, Frankfurt, Germany
Ben Freedman
2   Heart Research Institute, Charles Perkins Centre, University of Sydney, Sydney, Australia
3   Department of Cardiology, Concord Hospital, Sydney, Australia
4   ANZAC Research Institute, Concord Hospital, Sydney, Australia
› Author Affiliations
Funding None.


Background It is uncertain whether stroke risk of asymptomatic ambulatory atrial fibrillation (AA-AF) incidentally detected in primary care is comparable with other clinical AF presentations in primary care or hospital.

Methods The stoke risk of 22,035 patients with incident nonvalvular AF from the United Kingdom primary care Clinical Practice Research Datalink with linkage to hospitalization and mortality data was compared with 23,605 controls without AF (age- and sex-matched 5:1 to 5,409 AA-AF patients). Incident AF included 5,913 with symptomatic ambulatory AF (SA-AF); 4,989 with primary and 5,724 with nonprimary hospital AF discharge diagnosis (PH-AF and non-PH-AF); and 5,409 with AA-AF. Ischemic stroke adjusted subhazard ratios (aSHRs) within 3 years of AA-AF were compared with SA-AF, PH-AF, non-PH-AF, and no AF, accounting for mortality as competing risk and adjusted for ischemic stroke risk factors.

Results There were 1,026 ischemic strokes in 49,544 person-years in patients with incident AF (crude incidence rate: 2.1 ischemic strokes/100 person-years). Ischemic stroke aSHR over 3 years showed no differences between AA-AF and SA-AF, PH-AF, and non-PH-AF groups (aSHR: 0.87–1.01 vs. AA-AF). All AF groups showed a significantly higher aSHR compared with no AF.

Conclusion Ischemic stroke risk in patients with AA-AF incidentally detected in primary care is far from benign, and not less than incident AF presenting clinically in general practice or hospital. This provides justification for identification of previously undetected AF, e.g., by opportunistic screening, and subsequent stroke prevention with thromboprophylaxis, to reduce the approximately 10% of ischemic strokes related to unrecognized AF.

Author Contributions

All authors had full access to all the data in the study and C.M. takes responsibility for the integrity of the data and accuracy of the data analysis. Conception or design: all authors. Data acquisition and analysis: C.M., C.W. Data interpretation: all authors. Drafting of the manuscript: all authors. Critical revision for important intellectual content: all authors. Final approval of the version to be submitted: all authors.

Data Availability

Clinical Practice Research Datalink data cannot be shared because of licensing restrictions.


The views expressed are those of the authors and not official positions of the institutions. Part of the information reported in this manuscript was presented at the European Society of Cardiology Congress, August 26–30, 2017, Barcelona, Spain.

Ethical Approval

The study protocol was approved by the Independent Scientific Advisory Committee for CPRD research (Protocol 11_024RAMn). No further ethics approval was required for the analysis of the data as the CPRD Group had obtained ethical approval from a multicenter research ethics committee for all purely observational research using CPRD data, namely, studies that do not include patient involvement. Data that could directly identify patients were not collected in this study.

Supplementary Material

Publication History

Received: 10 February 2021

Accepted: 28 June 2021

Accepted Manuscript online:
30 June 2021

Article published online:
24 August 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Freedman B, Potpara TS, Lip GY. Stroke prevention in atrial fibrillation. Lancet 2016; 388 (10046): 806-817
  • 2 Lowres N, Olivier J, Chao TF. et al. Estimated stroke risk, yield, and number needed to screen for atrial fibrillation detected through single time screening: a multicountry patient-level meta-analysis of 141,220 screened individuals. PLoS Med 2019; 16 (09) e1002903
  • 3 Freedman B, Camm J, Calkins H. et al; AF-Screen Collaborators. Screening for atrial fibrillation: a report of the AF-SCREEN International Collaboration. Circulation 2017; 135 (19) 1851-1867
  • 4 Freedman B, Schnabel R, Calkins H. Opportunistic electrocardiogram screening for atrial fibrillation to prevent stroke. JAMA Cardiol 2019; 4 (02) 91-92
  • 5 Brieger D, Amerena J, Attia JR. et al. National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the diagnosis and management of atrial fibrillation 2018. Med J Aust 2018; 209 (08) 356-362
  • 6 Kirchhof P, Benussi S, Kotecha D. et al; ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37 (38) 2893-2962
  • 7 Curry SJ, Krist AH, Owens DK. et al; US Preventive Services Task Force. Screening for atrial fibrillation with electrocardiography: US Preventive Services Task Force recommendation statement. JAMA 2018; 320 (05) 478-484
  • 8 Martinez C, Katholing A, Freedman SB. Adverse prognosis of incidentally detected ambulatory atrial fibrillation. A cohort study. Thromb Haemost 2014; 112 (02) 276-286
  • 9 Freedman B, Martinez C, Katholing A, Rietbrock S. Residual risk of stroke and death in anticoagulant-treated patients with atrial fibrillation. JAMA Cardiol 2016; 1 (03) 366-368
  • 10 Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40 (05) 373-383
  • 11 Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94 (446) 496-509
  • 12 January CT, Wann LS, Calkins H. et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019; 140 (02) e125-e151
  • 13 Lip GYH, Banerjee A, Boriani G. et al. Antithrombotic therapy for atrial fibrillation: CHEST guideline and expert panel report. Chest 2018; 154 (05) 1121-1201
  • 14 Flaker GC, Belew K, Beckman K. et al; AFFIRM Investigators. Asymptomatic atrial fibrillation: demographic features and prognostic information from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Am Heart J 2005; 149 (04) 657-663
  • 15 Boriani G, Laroche C, Diemberger I. et al. Asymptomatic atrial fibrillation: clinical correlates, management, and outcomes in the EORP-AF Pilot General Registry. Am J Med 2015; 128 (05) 509.e2-518.e2
  • 16 Potpara TS, Polovina MM, Marinkovic JM, Lip GY. A comparison of clinical characteristics and long-term prognosis in asymptomatic and symptomatic patients with first-diagnosed atrial fibrillation: the Belgrade Atrial Fibrillation Study. Int J Cardiol 2013; 168 (05) 4744-4749
  • 17 Xiong Q, Proietti M, Senoo K, Lip GY. Asymptomatic versus symptomatic atrial fibrillation: a systematic review of age/gender differences and cardiovascular outcomes. Int J Cardiol 2015; 191: 172-177
  • 18 Martinez C, Katholing A, Wallenhorst C, Granziera S, Cohen AT, Freedman SB. Increasing incidence of non-valvular atrial fibrillation in the UK from 2001 to 2013. Heart 2015; 101 (21) 1748-1754
  • 19 Hindricks G, Potpara T, Dagres N. et al; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42 (05) 373-498
  • 20 Freedman B, Hindricks G, Banerjee A. et al. World Heart Federation roadmap on atrial fibrillation – a 2020 update. Glob Heart 2021; 16 (01) 41
  • 21 Siontis KC, Gersh BJ, Killian JM. et al. Typical, atypical, and asymptomatic presentations of new-onset atrial fibrillation in the community: characteristics and prognostic implications. Heart Rhythm 2016; 13 (07) 1418-1424
  • 22 Herrett E, Gallagher AM, Bhaskaran K. et al. Data resource profile: Clinical Practice Research Datalink (CPRD). Int J Epidemiol 2015; 44 (03) 827-836
  • 23 Cowan JC, Wu J, Hall M, Orlowski A, West RM, Gale CP. A 10 year study of hospitalized atrial fibrillation-related stroke in England and its association with uptake of oral anticoagulation. Eur Heart J 2018; 39 (32) 2975-2983
  • 24 Freedman B. Major progress in anticoagulant uptake for atrial fibrillation at last: does it translate into stroke prevention?. Eur Heart J 2018; 39 (32) 2984-2986