Download PDF
Thromb Haemost 2009; 101(05): 938-942
DOI: 10.1160/TH08-10-0635
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Gender differences in stroke risk of atrial fibrillation patients on oral anticoagulant treatment

Daniela Poli
1   Department of Medical and Surgical Critical Care, University of Florence and Department of Heart and Vessels, Thrombosis Centre, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
,
Emilia Antonucci
1   Department of Medical and Surgical Critical Care, University of Florence and Department of Heart and Vessels, Thrombosis Centre, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
,
Elisa Grifoni
1   Department of Medical and Surgical Critical Care, University of Florence and Department of Heart and Vessels, Thrombosis Centre, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
,
Rosanna Abbate
1   Department of Medical and Surgical Critical Care, University of Florence and Department of Heart and Vessels, Thrombosis Centre, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
,
Gian Franco Gensini
1   Department of Medical and Surgical Critical Care, University of Florence and Department of Heart and Vessels, Thrombosis Centre, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
2   Centro S. Maria agli Ulivi, Fondazione Don Carlo Gnocchi Onlus IRCCS, Impruneta, Florence, Italy
,
Domenico Prisco
1   Department of Medical and Surgical Critical Care, University of Florence and Department of Heart and Vessels, Thrombosis Centre, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
› Author Affiliations
Further Information

Publication History

Received: 02 October 2008

Accepted after major revision: 12 February 2009

Publication Date:
24 November 2017 (online)

    Permissions and Reprints

Summary

The efficacy of adjusted-dose oral anticoagulant treatment (OAT) in the prevention of stroke in atrial fibrillation (AF) is well documented. Available data show that AF patients are widely heterogeneous in terms of ischaemic stroke risk. The role of female gender as a predictor of stroke risk is inconsistent, in particular it is unclear if warfarin treatment is able to prevent stroke equally in both sexes. We performed a prospective study on 780 AF patients on OAT, followed by an Anticoagulation Clinic, to evaluate if female gender is a risk factor for stroke among patients on OAT and if the quality of anticoagulation is different between genders. No difference was found in relation to the quality of anticoagulation between genders (p=0.5). During follow-up 33 patients had major bleedings (rate 1.37x100 pt/yrs) but no difference was found between genders in bleeding risk. Forty patients had ischaemic events [rate 1.66x100 pt/yrs; males rate 1.2 x100 pt/yrs; females rate 2.43x100 pt/yrs; p=0.042; relative risk (RR) of females vs. males 2.0 (95% confidence interval [CI] 1.3–3.1); p= 0.004]. The higher rate of ischaemic events in females with respect to males was confirmed at Cox regression analysis after correction for age (p=0.009). In addition, strokes occurring in females were more disabling, and RR for severe and fatal stroke, defined according to Modified Rankin scale, of females vs. males was 3.1 (95% CI 1.3–6.5; p=0.001). In conclusion, our data show a higher risk of stroke in anticoagulated AF females with respect to males, despite a similar quality of anticoagulation.

Keywords

Atrial fibrillation - stroke - warfarin - female gender - quality of anticoagulation
 

  • References

  • 1 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.
    CrossrefPubMedGoogle Scholar
  • 2 Gage BF, van Walraven C, Pearce L. et al. Selecting patients with atrial fibrillation for anticoagulation: stroke risk stratification in patients taking aspirin. Circulation 2004; 110: 2287-2292.
    CrossrefPubMedGoogle Scholar
  • 3 Lip GY, Watson T, Shantsila E. Anticoagulation for stroke prevention in atrial fibrillation: is gender important?. Eur Heart J 2006; 27: 1893-1894.
    CrossrefPubMedGoogle Scholar
  • 4 Hart RG, Pearce LA, McBride R. et al. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Stroke 1999; 30: 1223-1229.
    CrossrefPubMedGoogle Scholar
  • 5 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 Framing-ham Heart Study. J Am Med Assoc 2003; 290: 1049-1056.
    CrossrefPubMedGoogle Scholar
  • 6 Hughes M, Lip GY. Guideline Development Group, National Clinical Guideline for Management of Atrial Fibrillation in Primary and Secondary Care, National Institute for Health and Clinical Excellence.. Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thromb Haemost 2008; 99: 295-304.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Aronow WS, Gutstein H, Hsieh FY. Risk factors for thromboembolic stroke in elderly patients with chronic atrial fibrillation. Am J Cardiol 1989; 63: 366-667.
    CrossrefPubMedGoogle Scholar
  • 8 Petersen P, Kastrup J, Helweg-Larsen S. et al. Risk factors for thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Arch Intern Med 1990; 150: 819-821.
    CrossrefPubMedGoogle Scholar
  • 9 Aronow WS, Ahn C, Kronzon I. et al. Risk factors for new thromboembolic stroke in patients > or = 62 years of age with chronic atrial fibrillation. Am J Cardiol 1998; 82: 119-121.
    CrossrefPubMedGoogle Scholar
  • 10 Nakagami H, Yamamoto K, Ikeda U. et al. Mitral regurgitation reduces the risk of stroke in patients with nonrheumatic atrial fibrillation. Am Heart J 1998; 136: 528-532.
    CrossrefPubMedGoogle Scholar
  • 11 The SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators.. Patients with nonvalvular atrial fibrillation at low risk of stroke during treatment with aspirin: Stroke Prevention in Atrial Fibrillation III Study. J Am Med Assoc 1998; 279: 1273-1277.
    CrossrefPubMedGoogle Scholar
  • 12 Fang MC, Singer DE, Chang Y. et al. Gender differences in the risk of ischemic stroke and peripheral embolism in atrial fibrillation: the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) study. Circulation 2005; 112: 1687-1691.
    CrossrefPubMedGoogle Scholar
  • 13 Hughes M, Lip GY. Guideline Development Group for the NICE national clinical guideline for management of atrial fibrillation in primary and secondary care.. Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review. Q J Med 2007; 100: 599-607.
    CrossrefPubMedGoogle Scholar
  • 14 Poli D, Antonucci E, Grifoni E. et al. Stroke risk in atrial fibrillation patients on warfarin: predictive ability of risk stratification schemes for primary and secondary prevention. Thromb Haemost 2009; 101: 367-372.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Albers GW, Dalen JE, Laupacis A. et al. Antithrombotic therapy in atrial fibrillation. Chest 2001; 119: 194S-206S.
    CrossrefPubMedGoogle Scholar
  • 16 Iliceto S. A guide to Oral Anticoagulant Therapy: Recommendation of Italian Federation of Anticoagulation Clinics. Haematologica 2003; 88 (02) 1.
    PubMedGoogle Scholar
  • 17 Poller L, Keown M, Ibrahim S. et al. An international multicenter randomized study of computer-assisted oral anticoagulant dosage vs. medical staff dosage. J Thromb Haemost 2008; 06: 935-943.
    CrossrefPubMedGoogle Scholar
  • 18 Rosendaal FR, Cannegieter SC, van der Meer FJM. et al. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69: 236-239.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Bonita R, Beaglehole R. Modification of Rankin scale: recovery of motor function after stroke. Stroke 1988; 19: 1497-1500.
    CrossrefPubMedGoogle Scholar
  • 20 Palareti G, Leali N, Coccheri S. et al. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (IS-COAT). Italian Study on Complications of Oral Anticoagulant Therapy. Lancet 1996; 348: 423-428.
    CrossrefPubMedGoogle Scholar
  • 21 Gage BF, Waterman AD, Shannon W. et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation. J Am Med Assoc 2001; 285: 2864-2870.
    CrossrefPubMedGoogle Scholar
  • 22 Rothman KJ, Greenland S. Modern Epidemiology. 2nd ed. Philadelphia: Lippincott-Raven; 1998
    Google Scholar
  • 23 Rothman KJ. Epidemiology. Chap. 3, Ed. Oxford University; 2002. p. 46-49.
    Google Scholar
  • 24 Poli D, Antonucci E, Marcucci R. et al. The quality of anticoagulation on functional outcome and mortality for TIA/stroke in atrial fibrillation patients. Int J Cardiol 2009; 132: 109-113.
    CrossrefPubMedGoogle Scholar
  • 25 Pengo V, Legnani C, Noventa F. et al. Oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and risk of bleeding. A Multicenter Inception Cohort Study. Thromb Haemost 2001; 85: 418-422.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Gomberg-Maitland M, Wenger NK, Feyzi J. et al. Anticoagulation in women with non-valvular atrial fibrillation in the stroke prevention using an oral thrombin inhibitor (SPORTIF) trials. Eur Heart J 2006; 27: 1947-1953.
    CrossrefPubMedGoogle Scholar
  • 27 Poli D, Antonucci E, Cecchi E. et al. Culprit factors for the failure of well-conducted warfarin therapy to prevent ischemic events in patients with atrial fibrillation: the role of homocysteine. Stroke 2005; 36: 2159-2163.
    CrossrefPubMedGoogle Scholar
  • 28 Seidl K, Hauer B, Schwick NG. et al. Risk of thromboembolic events in patients with atrial flutter. Am J Cardiol 1998; 82: 580-583.
    CrossrefPubMedGoogle Scholar
  • 29 Nichol MB, Knight TK, Dow T. et al. Quality of anticoagulation monitoring in nonvalvular atrial fibrillation patients: comparison of anticoagulation clinic versus usual care. Ann Pharmacother 2008; 04: 62-70.
    PubMedGoogle Scholar
  • 30 Chiquette E, Amato MG, Bussey HI. Comparison of an anticoagulation clinic with usual medical care: anticoagulation control, patient outcomes, and health care costs. Arch Intern Med 1998; 158: 1641-1647.
    CrossrefPubMedGoogle Scholar
  • 31 Fang MC, Chang Y, Hylek EM. et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med 2004; 141: 745-752.
    CrossrefPubMedGoogle Scholar
  • 32 Schulman S, Beyth RJ, Kearon C. et al. American College of Chest Physicians.. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133: 257S-298S.
    CrossrefPubMedGoogle Scholar
  • 33 White HD, Gruber M, Feyzi J. et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med 2007; 167: 239-245.
    CrossrefPubMedGoogle Scholar
  • 34 Hylek EM, Go AS, Chang Y. et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003; 349: 1019-1026.
    CrossrefPubMedGoogle Scholar
  • 35 Oden A, Fahlen M, Hart RG. Optimal INR for prevention of stroke and death in atrial fibrillation: a critical appraisal. Thromb Res 2006; 117: 493-499.
    CrossrefPubMedGoogle Scholar