Download PDF
Thromb Haemost 2020; 120(06): 894-898
DOI: 10.1055/s-0040-1710014
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Female Sex as a Risk Modifier for Stroke Risk in Atrial Fibrillation: Using CHA2DS2-VASc versus CHA2DS2-VA for Stroke Risk Stratification in Atrial Fibrillation: A Note of Caution

Peter Brønnum Nielsen
1   Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
2   Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark
,
Thure Filskov Overvad 
2   Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark
3   Department of Oncology, Aalborg University Hospital, Aalborg, Denmark
› Author Affiliations
Further Information

Publication History

21 February 2020

17 March 2020

Publication Date:
21 April 2020 (online)

Also available at
   Permissions and Reprints

Abstract

Stroke prevention is a key clinical concern in the management of patients with atrial fibrillation. Oral anticoagulation treatment reduces the risk of disabling stroke, but the treatment increases the risk of bleeding. For decades, the decision to initiate oral anticoagulation has been guided by clinical risk scoring systems such as the CHADS2 and CHA2DS2-VASc scores. In this narrative review, we focus on the recent discussion of the “Sc” (Sex Category) criterion in the CHA2DS2-VASc score. Epidemiological considerations when assessing stroke rates in cohorts are discussed, and the implications of different methodological approaches are outlined. Next, we review studies investigating the association of the “Sc” criterion on the stroke rates under various approaches. Lastly, we discuss potential consequences of implementing the recently suggested sex-less CHA2DS2-VA score, which leaves out female sex from stroke risk assessment in atrial fibrillation.

Keywords

stroke/prevention - cardiology - epidemiological studies
 

  • References

  • 1 Proietti M, Mujovic N, Potpara TS. Optimizing stroke and bleeding risk assessment in patients with atrial fibrillation: a balance of evidence, practicality and precision. Thromb Haemost 2018; 118 (12) 2014-2017
    Thieme ConnectPubMedSearch in Google Scholar
  • 2 Lip G, Freedman B, De Caterina R, Potpara TS. Stroke prevention in atrial fibrillation: past, present and future. Comparing the guidelines and practical decision-making. Thromb Haemost 2017; 117 (07) 1230-1239
    Thieme ConnectPubMedSearch in Google Scholar
  • 3 Lega J-C, Bertoletti L, Gremillet C. , et al. Consistency of safety and efficacy of new oral anticoagulants across subgroups of patients with atrial fibrillation. PLoS One 2014; 9 (03) e91398
    CrossrefPubMedSearch in Google Scholar
  • 4 Delluc A, Wang TF, Yap ES. , et al. Anticoagulation of cancer patients with non-valvular atrial fibrillation receiving chemotherapy: guidance from the SSC of the ISTH. J Thromb Haemost 2019; 17 (08) 1247-1252
    CrossrefPubMedSearch in Google Scholar
  • 5 Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. JAMA 2001; 285 (22) 2864-2870
    CrossrefPubMedSearch in Google Scholar
  • 6 Borre ED, Goode A, Raitz G. , et al. Predicting thromboembolic and bleeding event risk in patients with non-valvular atrial fibrillation: a systematic review. Thromb Haemost 2018; 118 (12) 2171-2187
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Chiang C-E, Okumura K, Zhang S. , et al. 2017 consensus of the Asia Pacific Heart Rhythm Society on stroke prevention in atrial fibrillation. J Arrhythm 2017; 33 (04) 345-367
    PubMedSearch in Google Scholar
  • 8 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
    CrossrefPubMedSearch in Google Scholar
  • 9 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. J Am Coll Cardiol 2019; 74 (01) 104-132
    CrossrefPubMedSearch in Google Scholar
  • 10 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
    CrossrefPubMedSearch in Google Scholar
  • 11 Brieger D, Amerena J, Attia J. , et al. National Heart foundation of australia and the cardiac society of australia and new zealand: australian clinical guidelines for the diagnosis and management of atrial fibrillation 2018. Heart Lung Circ 2018; 27 (10) 1209-1266
    CrossrefPubMedSearch in Google Scholar
  • 12 Allan V, Banerjee A, Shah AD. , et al. Net clinical benefit of warfarin in individuals with atrial fibrillation across stroke risk and across primary and secondary care. Heart 2017; 103 (03) 210-218
    CrossrefPubMedSearch in Google Scholar
  • 13 Nielsen PB, Larsen TB, Skjøth F, Overvad TF, Lip GY. Stroke and thromboembolic event rates in atrial fibrillation according to different guideline treatment thresholds: a nationwide cohort study. Sci Rep 2016; 6: 27410
    CrossrefPubMedSearch in Google Scholar
  • 14 Quinn GR, Severdija ON, Chang Y, Singer DE. Wide variation in reported rates of stroke across cohorts of patients with atrial fibrillation. Circulation 2017; 135 (03) 208-219
    CrossrefPubMedSearch in Google Scholar
  • 15 Nielsen PB, Lip GYH. Adding rigor to stroke rate investigations in patients with atrial fibrillation. Circulation 2017; 135 (03) 220-223
    CrossrefPubMedSearch in Google Scholar
  • 16 Nielsen PB, Chao T-F. The risks of risk scores for stroke risk assessment in atrial fibrillation. Thromb Haemost 2015; 113 (06) 1170-1173
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Heidbuchel H. The search for the tipping point on when to anticoagulate patients with atrial fibrillation. Heart 2017; 103 (03) 181-183
    CrossrefPubMedSearch in Google Scholar
  • 18 Friberg L, Skeppholm M, Terént A. Benefit of anticoagulation unlikely in patients with atrial fibrillation and a CHA2DS2-VASc score of 1. J Am Coll Cardiol 2015; 65 (03) 225-232
    CrossrefPubMedSearch in Google Scholar
  • 19 Maeda T, Nishi T, Funakoshi S. , et al. Risks of bleeding and stroke based on CHA2DS2-VASc scores in Japanese patients with atrial fibrillation: a large-scale observational study using real-world data. J Am Heart Assoc 2020; 9 (05) e014574
    PubMedSearch in Google Scholar
  • 20 Nielsen PB, Larsen TB, Lip GYH. Misconceptions on interpretation of risk prediction tools in atrial fibrillation. Am J Med 2016; 129 (05) e31
    PubMedSearch in Google Scholar
  • 21 Yoon M, Yang PS, Jang E. , et al. Dynamic changes of CHA2DS2-VASc score and the risk of ischaemic stroke in asian patients with atrial fibrillation: a nationwide cohort study. Thromb Haemost 2018; 118 (07) 1296-1304
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 Chao TF, Liao JN, Tuan TC. , et al. Incident co-morbidities in patients with atrial fibrillation initially with a CHA2DS2-VASc score of 0 (males) or 1 (females): implications for reassessment of stroke risk in initially ‘low-risk’ patients. Thromb Haemost 2019; 119 (07) 1162-1170
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Wang TJ, Massaro JM, Levy D. , et al. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. JAMA 2003; 290 (08) 1049-1056
    CrossrefPubMedSearch in Google Scholar
  • 24 Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology 2007; 69 (06) 546-554
    CrossrefPubMedSearch in Google Scholar
  • 25 Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; 137 (02) 263-272
    CrossrefPubMedSearch in Google Scholar
  • 26 Marzona I, Proietti M, Farcomeni A. , et al. Sex differences in stroke and major adverse clinical events in patients with atrial fibrillation: a systematic review and meta-analysis of 993,600 patients. Int J Cardiol 2018; 269: 182-191
    CrossrefPubMedSearch in Google Scholar
  • 27 Inoue H, Atarashi H, Okumura K. , et al; J-RHYTHM Registry Investigators. Impact of gender on the prognosis of patients with nonvalvular atrial fibrillation. Am J Cardiol 2014; 113 (06) 957-962
    CrossrefPubMedSearch in Google Scholar
  • 28 Tomasdottir M, Friberg L, Hijazi Z, Lindbäck J, Oldgren J. Risk of ischemic stroke and utility of CHA2 DS2 -VASc score in women and men with atrial fibrillation. Clin Cardiol 2019; 42 (10) 1003-1009
    CrossrefPubMedSearch in Google Scholar
  • 29 Nielsen PB, Skjøth F, Overvad TF, Larsen TB, Lip GYH. Female sex is a risk modifier rather than a risk factor for stroke in atrial fibrillation: should we use a CHA2DS2-VA score rather than CHA2DS2-VASc?. Circulation 2018; 137 (08) 832-840
    CrossrefPubMedSearch in Google Scholar
  • 30 Tomita H, Okumura K, Inoue H. , et al; J-RHYTHM Registry Investigators. Validation of risk scoring system excluding female sex from CHA2DS2-VASc in Japanese patients with nonvalvular atrial fibrillation – subanalysis of the J-RHYTHM registry. Circ J 2015; 79 (08) 1719-1726
    CrossrefPubMedSearch in Google Scholar
  • 31 Brieger D, Amerena J, Attia J. , et al; NHFA CSANZ Atrial Fibrillation Guideline Working Group. National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand: Australian Clinical Guidelines for the Diagnosis and Management of Atrial Fibrillation 2018. Heart Lung Circ 2018; 27 (10) 1209-1266
    CrossrefPubMedSearch in Google Scholar
  • 32 Linde C, Bongiorni MG, Birgersdotter-Green U. , et al. Sex differences in cardiac arrhythmia: a consensus document of the European Heart Rhythm Association, endorsed by the Heart Rhythm Society and Asia Pacific Heart Rhythm Society. Europace 2018; 20 (10) 1565-1565ao
    CrossrefPubMedSearch in Google Scholar
  • 33 Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GY. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 2010; 123 (07) 638-645.e4
    CrossrefPubMedSearch in Google Scholar
  • 34 Hsu JC, Maddox TM, Kennedy KF. , et al. Oral anticoagulant therapy prescription in patients with atrial fibrillation across the spectrum of stroke risk: insights from the NCDR PINNACLE registry. JAMA Cardiol 2016; 1 (01) 55-62
    CrossrefPubMedSearch in Google Scholar
  • 35 Thompson LE, Maddox TM, Lei L. , et al. Sex differences in the use of oral anticoagulants for atrial fibrillation: a report from the National Cardiovascular Data Registry (NCDR®) PINNACLE Registry. J Am Heart Assoc 2017; 6 (07) pii : e005801
    PubMedSearch in Google Scholar
  • 36 Pilcher SM, Alamneh EA, Chalmers L, Bereznicki LR. The Tasmanian Atrial Fibrillation Study (TAFS): differences in stroke prevention according to sex. Ann Pharmacother 2020; 1060028020904969
    PubMedSearch in Google Scholar
  • 37 Essien UR, Magnani JW, Chen N, Gellad WF, Fine MJ, Hernandez I. Race/ethnicity and sex-related differences in direct oral anticoagulant initiation in newly diagnosed atrial fibrillation: a retrospective study of medicare data. J Natl Med Assoc 2020; 112 (01) 103-108
    PubMedSearch in Google Scholar
  • 38 Hylek EM. Treatment persistence in atrial fibrillation: the next major hurdle. Thromb Haemost 2018; 118 (12) 2018-2019
    Thieme ConnectPubMedSearch in Google Scholar
  • 39 Pritchett RV, Bem D, Turner GM. , et al. Improving the prescription of oral anticoagulants in atrial fibrillation: a systematic review. Thromb Haemost 2019; 119 (02) 294-307
    Thieme ConnectPubMedSearch in Google Scholar
  • 40 Zielinski GD, van Rein N, Teichert M. , et al. Persistence of oral anticoagulant treatment for atrial fibrillation in the Netherlands: A surveillance study. Res Pract Thromb Haemost 2019; 4 (01) 141-153
    PubMedSearch in Google Scholar
  • 41 Overvad TF, Potpara TS, Nielsen PB. Stroke Risk Stratification: CHA2DS2-VA or CHA2DS2-VASc?. Heart Lung Circ 2019; 28 (02) e14-e15
    CrossrefPubMedSearch in Google Scholar