Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation
Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007;115:2689.
ABSTRACT: 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.
Catch 22: Warfarin For Stroke Prevention in Elderly Patients with Atrial Fibrillation
Review by Ranjith Shetty, MD
Is warfarin safe to use for stroke prevention in elderly patients with atrial fibrillation?
This cohort study investigated the rate of major hemorrhage in patients at warfarin initiation to define the risk of bleeding in the first year of therapy. Patients more than 65 years old with atrial fibrillation who were new to warfarin were eligible. Patients on the stroke or surgical service were not included due to higher baseline risk of bleeding.
Outcomes included major hemorrhage, time to termination of warfarin, and physician reason for discontinuation
472 patients were enrolled. 47% were female, 54% were greater than 75 years of age and 32% were greater than 80 years of age. A total of 90% of patients > 80 years had a CHADS2 score of > 2 (Table 1).
Table 1.
Stroke Rates by CHADS2 Score* |
||
CHADS2 Score |
Risk |
Stroke Rate Per Year |
0 |
Low |
1% |
1 |
Low |
1.5% |
2 |
Moderate |
2.5% |
3 |
High |
5% |
> 3 |
Very high |
>7% |
* Score determined by: CHF, hypertension, age >75, and/or diabetes = 1 point; stroke or TIA = 2 points. (Gage et al. JAMA 2001;285:2864-2870)
During the study, INR was in the therapeutic range of 2.0 to 3.0 58% of the time. During the first year, 26 patients sustained a major hemorrhage. The rate of major hemorrhage was 7.2 per 100 person-years (95% CI 4.9 to 10.6). Patients greater than 80 years old had higher rates of major hemorrhage than those younger (13.08 per 100 person-years versus 4.75 per 100 person-years, P=0.010). 15 (58%) of the major hemorrhages occurred within 90 days of warfarin initiation, 11 (42%) occurred within 30 days, and 7 (27%) occurred within the first 2 weeks. 12 (46%) of the major bleeding events occurred with concomitant aspirin and warfarin therapy. The overall rate of major hemorrhage was higher in those with CHADS2 scores of > 3 (IRR 8.19, 95% CI 3.37 to 19.88).
This study shows a high proportion of serious bleeding incidents among elderly patients receiving wafarin therapy. In addition, there is an apparent increased risk of bleeding during the initiation phase of warfarin therapy. Even more concerning is that patients with a greater need for thrombotic therapy, based on CHADS2 score, also had a greater risk for bleeding. Clearly, the decision to start warfarin therapy in elderly patients is not an easy one and the risk and benefits need to be weighed carefully. Future studies which combine genetic and clinical information into the process of dosing warfarin may make this decision easier and the initiation of warfarin safer.
About Ranjith Shetty, MD: Dr. Shetty completed his internship and residency in internal medicine at Georgetown University. Having recently completed a 1-year Fellowship with the Venous Thromboembolism Research Group, Dr. Shetty is currently a Cardiology Fellow at the Medical College of Virginia in Richmond, VA.