This Article Free upon publication Full Text Full Text (PDF) CME: Take the course for this article: Circulation: May 29, 2007, Volume 115, Number 21 All Versions of this Article: 115/21/2689    most recent CIRCULATIONAHA.106.653048v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hylek, E. M. Articles by Regan, S. Search for Related Content PubMed PubMed Citation Articles by Hylek, E. M. Articles by Regan, S. Related Collections Coumarins Arrhythmias, clinical electrophysiology, drugs Anticoagulants

(Circulation. 2007;115:2689-2696.)
© 2007 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation

Elaine M. Hylek, MD, MPH; Carmella Evans-Molina, MD; Carol Shea, RN; Lori E. Henault, MPH; Susan Regan, PhD

From the Department of Medicine (E.M.H., L.E.H.), Section of General Internal Medicine-Research Unit, Boston University School of Medicine, Boston Medical Center, and Department of Medicine (C.S., S.R.), General Medicine Division, Massachusetts General Hospital, Boston, Mass; and Department of Medicine (C.E.-M.), University of Virginia, Charlottesville, Va.

Correspondence to Elaine M. Hylek, MD, MPH, Research Unit, Section of General Internal Medicine, Boston University School of Medicine, Boston Medical Center, 91 East Concord St, Suite 200, Boston, MA 02118. E-mail ehylek{at}bu.edu

Received July 21, 2006; accepted March 13, 2007.

Background— Warfarin is effective in the prevention of stroke in atrial fibrillation but is under used in clinical care. Concerns exist that published rates of hemorrhage may not reflect real-world practice. Few patients 80 years of age were enrolled in trials, and studies of prevalent use largely reflect a warfarin-tolerant subset. We sought to define the tolerability of warfarin among an elderly inception cohort with atrial fibrillation.

Methods and Results— Consecutive patients who started warfarin were identified from January 2001 to June 2003 and followed for 1 year. Patients had to be 65 years of age, have established care at the study institution, and have their warfarin managed on-site. Outcomes included major hemorrhage, time to termination of warfarin, and reason for discontinuation. Of 472 patients, 32% were 80 years of age, and 91% had 1 stroke risk factor. The cumulative incidence of major hemorrhage for patients 80 years of age was 13.1 per 100 person-years and 4.7 for those <80 years of age (P=0.009). The first 90 days of warfarin, age 80 years, and international normalized ratio (INR) 4.0 were associated with increased risk despite trial-level anticoagulation control. Within the first year, 26% of patients 80 years of age stopped taking warfarin. Perceived safety issues accounted for 81% of them. Rates of major hemorrhage and warfarin termination were highest among patients with CHADS₂ scores (an acronym for congestive heart failure, hypertension, age 75, diabetes mellitus, and prior stroke or transient ischemic attack) of 3.

Conclusions— Rates of hemorrhage derived from younger noninception cohorts underestimate the bleeding that occurs in practice. This finding coupled with the short-term tolerability of warfarin likely contributes to its underutilization. Stroke prevention among elderly patients with atrial fibrillation remains a challenging and pressing health concern.

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