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Study Shows Certain Elderly Patients on Warfarin Therapy are at Greater Risk for Traumatic Intracranial Bleeding


NEW YORK (Reuters Health) - Certain older patients on warfarin therapy are at greater risk than others for traumatic intracranial bleeding, Veterans Affairs researchers have reported.

In their study of elderly adults receiving warfarin for atrial fibrillation (AF), five factors - dementia, anemia, depression, anticonvulsant use, and labile international normalized ratio - each made patients more vulnerable to traumatic intracranial bleeding.

"Advanced age is a powerful risk factor for thromboembolic stroke in patients with AF, and oral anticoagulation reduces this risk by almost two-thirds in patients at risk," the authors wrote. "However, up to half of the eligible older adults with AF are not treated with anticoagulant therapy due to health care professionals' concerns about potential treatment-related harms."

The research team reviewed medical and administrative data for 31,951 U.S. veterans with AF. Patients were 75 or older andwere newly referred to an anticoagulation clinic for warfarin therapy. Most had comorbidities, including hypertension (82.5%), coronary artery disease (42.6%) and diabetes (33.8%).

During the 11-year study period, 2002 through 2012, the incidence rate of hospitalization for traumatic intracranial bleeding was 4.80 per 1,000 person-years. The incidence rates for any intracranial bleeding and ischemic stroke were 14.58 and 13.44, respectively, per 1,000 person-years, the researchers reported online March 9 in JAMA Cardiology.

After adjusting for age, sex, race/ethnicity, and common comorbidities, significant predictors for traumatic intracranial bleeding were dementia (hazard ratio 1.76, p<0.01), anemia (HR 1.23, p<0.05), depression (HR 1.30, p<0.05), anticonvulsant use (HR 1.35, p<0.05), and labile international normalized ratio (HR 1.33, p<0.05).

"The differential risk between traumatic intracranial bleeding and ischemic stroke for those on warfarin therapy was lower than in prior studies, although the rate of ischemic stroke in our population was still considerable," senior author Dr. John Dodson, director of the Geriatric Cardiology Program at New York University School of Medicine, New York City, told Reuters Health by email.

"Of note, the most commonly used stroke risk score, CHA2S2-VASc, does a poor job of predicting risk for traumatic intracranial bleeding," he added. "Therefore, the risk factors appear to be distinct."

"For the practicing clinician, I think our findings underscore the need for a personalized approach to patients, potentially incorporating the risk factors we identified for traumatic intracranial bleeding in conversations around the risk versus benefit of warfarin therapy," Dr. Dodson said.

Dr. Dodson further noted that several oral anticoagulants have been approved in recent years that don't require the dose adjustment and monitoring needed with warfarin. "When we began this study, these drugs were very new and we therefore did not have a sufficient length of observation to generate a large enough sample of patients taking these medications."

"There are also implantable devices that have recently been approved that exclude the left atrial appendage, which is where most cerebroembolic phenomena originate from the circulation. We cannot comment on the relative harms of either of these strategies compared with warfarin in our data set," he acknowledged."

The final option would be to not treat - that is, taking a conservative approach with no medications or procedure - in a patient at particularly high risk for treatment-related harms, if this is concordant with the patient's own preferences," he concluded.

Dr. Vivek Reddy, director of Cardiac Arrhythmia Services at the Mount Sinai Health System and professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City, also noted that clinicians have alternatives to warfarin. "We now have new oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban), but since they are also anticoagulants, it is unknown if the risk of traumatic bleeding would be lower in these patients," he told Reuters Health by email.

Of the mechanical left atrial appendage closure device, Dr. Reddy, who was not involved in the study, stated, "the data is quite compelling for patients that are not good candidates for oral anticoagulation - and the elderly population seems to be a population that would particularly benefit."

Dr. Reddy also pointed out, as did the authors, that the findings may not be applicable to women because 98% of those studied were men. He also observed that "virtually all (participants) were Caucasian, so it's not known if there would be differences for other ethnicities."

The National Institutes of Health and a number of other organizations supported this research. One coauthor reported disclosures.

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