Coumadin Outweighs Hemorrhage Risk in Older Afib Patients

SAN FRANCISCO, Aug. 4 -- Even though anticoagulation for atrial fibrillation may boost the chance of an intracranial bleed slightly in elderly patients, the benefits of the therapy outweigh the risk of a hemorrhage, according to researchers here.

In a retrospective study of more than 13,500 adults with non-valvular atrial fibrillation, hemorrhage rates rose with age, and were actually slightly higher among patients who were not taking Coumadin (warfarin), wrote Margaret C. Fang, M.D., M.P.H., of the University of California San Francisco, and colleagues.

The risk for hemorrhage rose "strikingly" after age 80, the authors reported in the Aug. 10 issue of the Journal of the American Geriatrics Society. But they also found the risks for other adverse events outweigh the risks for hemorrhage in patients on Coumadin.

"Our findings show that although older patients have a greater risk for hemorrhage, the overall likelihood of hemorrhage on warfarin is relatively small, especially when one considers the benefits of stroke prevention," said Dr. Fang, a hospitalist.

"Carefully monitored warfarin therapy can be used with reasonable safety in older patients," she added.

Dr. Fang and colleagues at Kaiser Permanente in Oakland and at Boston University and the Massachusetts General Hospital conducted a cohort study of 13,559 adults with non-valvular atrial fibrillation to assess whether older age could be independently associated with hemorrhage risk, regardless of anticoagulation status.

The study cohort was assembled from automated clinical and administrative databases using previously validated search algorithms. The investigators reviewed medical charts from patients who were hospitalized for major hemorrhage, defined as intracranial bleeding, fatal bleeding, bleeding requiring ?2 units of transfused blood, or bleeding involving a critical anatomic site.

They divided the patients into four age categories: under 60, 60-69, 70-79, and 80 and older. They also used multivariate Poisson regression modeling to see whether there was an association between hemorrhage rates and age, stratified by Coumadin use and adjusted for other clinical risk factors for hemorrhage.

The mean age of the cohort was 71 + 15. In all, 28% of the total person-years analyzed in the study were from patients 80 and older The investigators found that older patients were more likely to have risk factors for ischemic stroke, such as hypertension and coronary disease, and for hemorrhage, such as prior gastrointestinal hemorrhage, anemia, and renal insufficiency.

There were no significant differences in age-related INRs (international normalized ratios) of 4.0 or in high INR variability, however.

They identified a total of 170 major hemorrhages suffered during 15,300 person-years in patients on Coumadin therapy, and 162 major hemorrhages during 15,530 person-years in patients not on Coumadin therapy.

They found that after adjusting for potential risk factors for hemorrhage, hemorrhage rates still rose with older age, with an average increase in hemorrhage rate of 1.2 (95% confidence interval, 1.0-1.4) per older age category in patients taking Coumadin, and 1.5 (95% CI=1.3-1.8) in those not on Coumadin.

Rates of intracranial hemorrhages were also significantly higher among patients 80 and older, with an adjusted rate ratio of 1.8, (95% CI, 1.1-3.1) for those taking warfarin, and an adjusted rate ratio of 4.7, (95% CI, 2.4-9.2) for those not taking warfarin compared with patients younger than 80.

The fact that the age-related risk for hemorrhage was slightly attenuated but not eliminated after adjustment for hemorrhage risk factors suggests that there are other, as yet unidentified risk factors for hemorrhage associated with advanced age, the authors wrote.

As for the finding that hemorrhage rates were similar among patients, the authors suggested that "clinicians may selectively prescribe Coumadin for patients who have a lower intrinsic risk for hemorrhage. This probable selection effect was more apparent in extracranial hemorrhages, which clinicians may more easily predict than intracranial hemorrhages."

They recommended that because patients with atrial fibrillation tend to be older and have multiple comorbidities, physicians should take care to minimize the patients' modifiable risk factors for hemorrhage and avoid over-coagulation.

"These results also support vigilance when initially starting Coumadin therapy, although the absolute rates of major hemorrhage in this study were reassuringly low even in the oldest patients and comparable with rates reported in randomized trials," the investigators wrote.

"These findings indicate that well-managed Coumadin therapy can be used safely in clinical practice to achieve substantial benefit in reducing the risk of atrial fibrillation-associated ischemic stroke," they concluded.

The authors noted several limitations of the study:

• As an observational study of actual clinical practice, it was subject to non-standardized data collection, resulting in periods of missing warfarin exposure and unavailable INR data.
• Because Coumadin treatment was not randomly assigned, confounding by contraindication may occur in that physicians are less likely to anticoagulate patients at higher risk for hemorrhage.