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

Daniela Poli; Emilia Antonucci; Elisa Grifoni; Rosanna Abbate; Gian Franco Gensini; Domenico Prisco

doi:10.1160/TH08-10-0635

Thrombosis and Haemostasis, Table of Contents

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

¹Department 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

¹Department 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

¹Department 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

¹Department 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

¹Department of Medical and Surgical Critical Care, University of Florence and Department of Heart and Vessels, Thrombosis Centre, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

²Centro S. Maria agli Ulivi, Fondazione Don Carlo Gnocchi Onlus IRCCS, Impruneta, Florence, Italy

,

Domenico Prisco

¹Department 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

Abstract

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

Full Text

References

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.
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.
3 Lip GY, Watson T, Shantsila E. Anticoagulation for stroke prevention in atrial fibrillation: is gender important?. Eur Heart J 2006; 27: 1893-1894.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
15 Albers GW, Dalen JE, Laupacis A. et al. Antithrombotic therapy in atrial fibrillation. Chest 2001; 119: 194S-206S.
16 Iliceto S. A guide to Oral Anticoagulant Therapy: Recommendation of Italian Federation of Anticoagulation Clinics. Haematologica 2003; 88 (02) 1.
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.
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.
19 Bonita R, Beaglehole R. Modification of Rankin scale: recovery of motor function after stroke. Stroke 1988; 19: 1497-1500.
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.
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.
22 Rothman KJ, Greenland S. Modern Epidemiology. 2nd ed. Philadelphia: Lippincott-Raven; 1998
23 Rothman KJ. Epidemiology. Chap. 3, Ed. Oxford University; 2002. p. 46-49.
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.
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.
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.
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.
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.
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.
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.
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.
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 (8^th Edition). Chest 2008; 133: 257S-298S.
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.
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.
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.