Download PDF
Thromb Haemost 2014; 112(02): 276-286
DOI: 10.1160/TH4-04-0383
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Adverse prognosis of incidentally detected ambulatory atrial fibrillation

A cohort study
Carlos Martinez
1   Institute for Epidemiology, Statistics and Informatics GmbH, Frankfurt, Germany
,
Anja Katholing
1   Institute for Epidemiology, Statistics and Informatics GmbH, Frankfurt, Germany
,
Saul Benedict Freedman
2   Department of Cardiology Concord Hospital and Anzac Research Institute, Sydney Medical School, University of Sydney, Australia
› Author Affiliations
Further Information

Publication History

Received: 24 April 2014

Accepted after minor revision: 14 May 2014

Publication Date:
04 December 2017 (online)

Also available at
   Permissions and Reprints

Summary

It was the aim of this study to determine prognosis of incidentally detected ambulatory atrial fibrillation (IA-AF) and its response to antithrombotic therapy. We performed a cohort study of 5,555 patients with IA-AF (mean age 70.9 ± 10.1, 38.4% female) and 24,705 age- and gender-matched controls without AF followed three years using UK Clinical Practice Research Datalink. We measured incidence rates of stroke, all-cause mortality, myocardial infarction, major bleeding, and effect of antithrombotic therapy. Patients with IA-AF had mean CHA2DS2VASc score 2.5 ± 1.5, 73% with score ≥2. The stroke incidence rate (IR) was 19.4 (95% confidence interval 17.1 – 21.9)/1,000 person-years vs 8.4 (7.7 – 9.1) in controls (p<0.001), mortality 40.1 (36.8 – 43.6)/1,000 person-years vs 20.9 (19.8 – 22.0) in controls (p<0.001), and myocardial infarction 9.0 (7.5 – 10.8)/1,000 person-years vs 6.5 (5.9 – 7.2) in controls (p<0.001). IRs of all endpoints increased with age. Oral anticoagulant ± antiplatelet therapy received by 51.0% in year following IA-AF was associated with adjusted hazard ratio (HR) of 0.35 (0.17 – 0.71) for stroke, and 0.56 (0.36 – 0.85) for death compared to no therapy, while antiplatelet treatment was associated with a non-significant reduction of HR: 0.81 (0.51 – 1.29) for stroke, and 0.80 (0.55 – 1.15) for death, though both carried a similar small non-significant adjusted excess IR of major bleeding. In conclusion, asymptomatic AF detected incidentally is associated with a significant adverse effect on stroke and death, with reduction in both associated with oral anticoagulant but not antiplatelet treatment. This provides justification to assess cost-effectiveness of community screening to detect unknown AF.

 

  • References

  • 1 Miyasaka Y, Barnes ME, Gersh BJ. et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006; 114: 119-125.
    CrossrefPubMedSearch in Google Scholar
  • 2 Camm AJ, Lip GYH, Caterina RD. et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation. An update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33: 2719-2747.
    CrossrefPubMedSearch in Google Scholar
  • 3 Lin HJ, Wolf PA, Kelly-Hayes M. et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996; 27: 1760-1764.
    CrossrefPubMedSearch in Google Scholar
  • 4 Kimura K, Minematsu K, Yamaguchi T. Atrial fibrillation as a predictive factor for severe stroke and early death in 15,831 patients with acute ischaemic stroke. J Neurol Neurosurg Psychiatry 2005; 76: 679-683.
    CrossrefPubMedSearch in Google Scholar
  • 5 Benjamin EJMDS, Wolf PAMD, D’Agostino RBP. et al. Impact of Atrial Fibrillation on the Risk of Death: The Framingham Heart Study. Circulation 1998; 98: 946-952.
    CrossrefPubMedSearch in Google Scholar
  • 6 Wang TJ, Larson MG, Levy D. et al. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study. Circulation 2003; 107: 2920-2925.
    CrossrefPubMedSearch in Google Scholar
  • 7 Hannon N, Sheehan O, Kelly L. et al. Stroke associated with atrial fibrillation - incidence and early outcomes in the North Dublin population stroke study. Cerebrovasc Dis 2010; 29: 43-49.
    CrossrefPubMedSearch in Google Scholar
  • 8 Leyden JM, Kleinig TJ, Newbury J. et al. Adelaide stroke incidence study: declining stroke rates but many preventable cardioembolic strokes. Stroke 2013; 44: 1226-1231.
    CrossrefPubMedSearch in Google Scholar
  • 9 Bhatt A, Majid A, Razak A. et al. Predictors of Occult Paroxysmal Atrial Fibrillation in Cryptogenic Strokes Detected by Long-Term Noninvasive Cardiac Monitoring. Stroke Res Treatm. 2011 2100. Article ID 172074, doi 10.4061/2011/172074.
    PubMedSearch in Google Scholar
  • 10 Stahrenberg RMD, Weber-Kruger M, Seegers JMD. et al. Enhanced Detection of Paroxysmal Atrial Fibrillation by Early and Prolonged Continuous Holter Monitoring in Patients With Cerebral Ischemia Presenting in Sinus Rhythm. Stroke 2010; 41: 2884-2888.
    CrossrefPubMedSearch in Google Scholar
  • 11 Healey JS, Connolly SJ, Gold MR. et al. Subclinical Atrial Fibrillation and the Risk of Stroke. N Engl J Med 2012; 366: 120-129.
    CrossrefPubMedSearch in Google Scholar
  • 12 Hannon N, Sheehan O, Kelly L. et al. Stroke associated with atrial fibrillation--incidence and early outcomes in the north Dublin population stroke study. Cerebrovasc Dis 2010; 29: 43-49.
    CrossrefPubMedSearch in Google Scholar
  • 13 Deif B, Lowres N, Freedman SB. Screening for atrial fibrillation above age 65 detects an asymptomatic subset at high risk of stroke. Int J Cardiol 2013; 164: 371-372.
    CrossrefPubMedSearch in Google Scholar
  • 14 Medi C, Hankey GJ, Freedman SB. Stroke risk and antithrombotic strategies in atrial fibrillation. Stroke 2010; 41: 2705-2713.
    CrossrefPubMedSearch in Google Scholar
  • 15 Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857-867.
    CrossrefPubMedSearch in Google Scholar
  • 16 Glotzer TV, Daoud EG, Wyse DG. et al. The relationship between daily atrial tachyarrhythmia burden from implantable device diagnostics and stroke risk: the TRENDS study. Circ Arrhythm Electrophysiol 2009; 02: 474-480.
    CrossrefPubMedSearch in Google Scholar
  • 17 Flaker GC, Belew K, Beckman K. et al. 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: 657-663.
    CrossrefPubMedSearch in Google Scholar
  • 18 Stott DJ, Dewar RI, Garratt CJ. et al. RCPE UK Consensus Conference on ‘approaching the comprehensive management of atrial fibrillation: evolution or revolution?’. J R Coll Physicians Edinb 2012; 42: 34-35.
    CrossrefPubMedSearch in Google Scholar
  • 19 Fuster V, Ryden LE, Cannom DS. et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. J Am Coll Cardiol 2011; 57: e101-198.
    CrossrefPubMedSearch in Google Scholar
  • 20 Fuster V, Ryden LE, Cannom DS. et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114: e257-354.
    CrossrefPubMedSearch in Google Scholar
  • 21 January CT, Wann LS, Alpert JS. et al. 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 Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014 Epub ahead of print.
    PubMedSearch in Google Scholar
  • 22 Lowres N, Neubeck L, Redfern J. et al. Screening to identify unknown atrial fibrillation. A systematic review. Thromb Haemost 2013; 110: 213-222.
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 03: 692-694.
    CrossrefPubMedSearch in Google Scholar
  • 24 Satagopan JM, Ben-Porat L, Berwick M. et al. A note on competing risks in survival data analysis. Br J Cancer 2004; 91: 1229-1235.
    CrossrefPubMedSearch in Google Scholar
  • 25 Fine J, Gray R. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496-509.
    CrossrefPubMedSearch in Google Scholar
  • 26 Hastie T, Tibshirami R. Generalized additive models for medical research. Stat Methods Med Res 1995; 04: 187-196.
    CrossrefPubMedSearch in Google Scholar
  • 27 Wood SN. Modelling and smoothing parameter estimation with multiple quadratic penalties. J Royal Stat Soc 2000; 62: 413-428.
    CrossrefPubMedSearch in Google Scholar
  • 28 Olesen JB, Torp-Pedersen C, Hansen ML. et al. The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 score 0-1: a nationwide cohort study. Thromb Haemost 2012; 107: 1172-1179.
    Thieme ConnectPubMedSearch in Google Scholar
  • 29 Connolly SJ, Ezekowitz MD, Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
    CrossrefPubMedSearch in Google Scholar
  • 30 Patel MR, Mahaffey KW, Garg J. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891.
    CrossrefPubMedSearch in Google Scholar
  • 31 Granger CB, Alexander JH, McMurray JJ. et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-992.
    CrossrefPubMedSearch in Google Scholar
  • 32 Wyse DG, Waldo AL, DiMarco JP. et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002; 347: 1825-1833.
    CrossrefPubMedSearch in Google Scholar
  • 33 Tsadok MA, Jackevicius CA, Rahme E. et al. Sex Differences in Stroke Risk Among Older Patients With Recently Diagnosed Atrial Fibrillation. J Am Med Assoc 2012; 307: 1952-1958.
    CrossrefPubMedSearch in Google Scholar
  • 34 Mant J, Hobbs FD, Fletcher K. et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493-503.
    CrossrefPubMedSearch in Google Scholar
  • 35 Potpara TS, Polovina MM, Marinkovic JM. et al. 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: 4744-4749.
    CrossrefPubMedSearch in Google Scholar
  • 36 Rienstra M, Vermond RA, Crijns HJ. et al. for the RI. Asymptomatic persistent atrial fibrillation and outcome: Results of the RACE study. Heart Rhythm. 2014 Epub ahead of print.
    PubMedSearch in Google Scholar
  • 37 Banerjee A, Lane DA, Torp-Pedersen C. et al. Net clinical benefit of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus no treatment in a ‘real world’ atrial fibrillation population: a modelling analysis based on a nationwide cohort study. Thromb Haemost 2012; 107: 584-589.
    Thieme ConnectPubMedSearch in Google Scholar
  • 38 Olesen JB, Lip GY, Lindhardsen J. et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a ‘real world’ nationwide cohort study. Thromb Haemost 2011; 106: 739-749.
    Thieme ConnectPubMedSearch in Google Scholar
  • 39 Sjalander S, Sjalander A, Svensson PJ. et al. Atrial fibrillation patients do not benefit from acetylsalicylic acid. Europace 2014; 16: 631-638.
    CrossrefPubMedSearch in Google Scholar
  • 40 Hobbs FDR, Fitzmaurice DA, Mant J. et al. A randomised controlled trial and costeffectiveness study of systematic screening (targeted and total population screening) versus routine practice for the detection of atrial fibrillation in people aged 65 and over. The SAFE study. Health Technol Assess 2005; 09 iii-iv, ix-x 1-74.
    PubMedSearch in Google Scholar
  • 41 Lau JK, Lowres N, Neubeck L. et al. iPhone ECG application for community screening to detect silent atrial fibrillation: a novel technology to prevent stroke. Int J Cardiol 2013; 165: 193-194.
    CrossrefPubMedSearch in Google Scholar
  • 42 Lowres N, Freedman SB, Redfern J. et al. Screening Education And Recognition in Community pHarmacies of Atrial Fibrillation to prevent stroke in an ambulant population aged >=65 years (SEARCH-AF stroke prevention study): a cross-sectional study protocol. Br Med J Open 2012; 02: e0011355.
    PubMedSearch in Google Scholar