Gender Differences in Systemic Embolism Risk in Atrial Fibrillation
Abstract & Commentary
By John P. DiMarco, MD, PhD Dr. DiMarco is Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis and does research for Medtronic and Guidant.
Synopsis: Women have a higher risk than men for atrial fibrillation related thromboembolism that is independent of the presence of other risk factors.
Source: Fang MC, 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.
The anticoagulation and risk factors in atrial fibrillation (ATRIA) study is a cohort study in patients with diagnosed nonvalvular atrial fibrillation who receive care within a large integrated healthcare delivery system in northern California (Kaiser Permanente). The cohort was assembled between July 1996 and December 1997, and followed for a median of 2.4 years. This paper deals with the influence of gender on stroke risk in atrial fibrillation.
Fang and colleagues searched their database for hospitalization and billing claims related to ischemic stroke and peripheral embolism for all patients in the cohort. Events were individually validated by medical record review. Only outpatient events were counted, with in-hospital and procedure-related events excluded. The same method was used to identify patients who had hemorrhagic events, including both intracranial and extracranial hemorrhage. Clinical characteristics, laboratory studies, warfarin exposure, and other medications were obtained from the health system's administrative, pharmacy, and clinical databases.
The ATRIA cohort included 5795 women and 7764 men. The women were generally older and more likely to have a history of stroke or hypertension, but were less likely to have coronary artery disease or diabetes mellitus. The CHADS2 score, which includes congestive heart failure, hypertension, age, diabetes, and prior stroke or TIA as risk factors, was used to estimate baseline risk. Over 70% of the patients in both groups had a CHADS2 score of 0, 1, or 2.
During periods off warfarin therapy, 394 thromboembolic events were identified, including 369 ischemic strokes during 15,494 person years of follow-up. Women had a higher incidence rate of thromboembolism off warfarin than did men (3.5% vs 1.8%). The unadjusted rate ratio for women vs men was 1.9. These higher rates of thromboembolism were seen at all levels of the CHADS2 score index. When adjusted for other stroke risk factors, women continued to have a greater risk of thromboembolism than men, with an adjusted risk ratio of 1.6. Oral estrogen replacement therapy was not associated with the significantly increased risk of arterial thromboembolism. The increased risk among women was seen both for patients below age 75 and above age 75.
Among warfarin users, there were 204 thromboembolic events and 167 major hemorrhagic events over 15,000 person years of follow-up. The unadjusted annual rates of thromboembolism on warfarin were 1.5% in women and 1.2% in men. After multivariate analysis for other risk factors, warfarin therapy was associated with a reduction in the rate of thromboembolism, with an adjusted rate ratio of 0.4 in women and 0.6 in men. Annual rates of hemorrhage were similar between men and women (1.0% vs 1.1%).
Fang et al conclude that women have a higher risk than men for atrial fibrillation-related thromboembolism that is independent of the presence of other risk factors. Warfarin therapy is at least as effective in women as in men, and is not associated with a gender related increase in major bleeding events.
Commentary
Many of the recommendations regarding atrial fibrillation are based on observations made almost 20 years ago during randomized clinical trials of anticoagulation therapy in patients with nonvalvular atrial fibrillation. The data in this paper from a more recent large patient cohort provide continued support for the use of warfarin in patients with atrial fibrillation, and stress the importance of its use in women. Physicians are often reluctant to prescribe warfarin in elderly women. The risk of falls or cutaneous bleeding may be perceived to be higher in women than in men. However, this study and data from a recent randomized controlled trial, RACE, of rate control vs rhythm control, indicate that women are at higher risk than men for thromboembolic events (see J Am Coll Cardiol. 2005;46:1298-1306). These observations provide further support for the consistent use of warfarin in women with nonvalvular atrial fibrillation.
Women have a higher risk than men for atrial fibrillation related thromboembolism that is independent of the presence of other risk factors.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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