Large Study Looks at Risks of Atrial Fibrillation Treatment
By Brenda L. Mooney
NEW YORK — Worried that a fall might lead to traumatic intracranial bleeding, many physicians are wary of prescribing warfarin to older adults with atrial fibrillation (AFib).
New research on veterans does nothing to put those concerns to rest.
In fact, the study published recently in JAMA Cardiology found that the rate of traumatic intracranial bleeding among older adults with AFib initiating warfarin therapy actually was higher than previously reported in clinical trials.1
On the other hand, background information in the report noted that older age is a significant risk factor for thromboembolic stroke in patients with AFib and that drug therapy with warfarin reduces the threat by almost two-thirds in patients at high risk.
Study authors led by John A. Dodson, MD, MPH, of New York University School of Medicine, emphasized that as many as half of eligible older adults with AFib are not treated with anticoagulant therapy due to healthcare professionals’ worry about potential treatment-related harms. The primary concern, according to past research, is related to the risk of falling, which could cause traumatic intracranial bleeding, a devastating condition in older patients.
“Despite such concerns, the incidence and determinants of this outcome among older adults with AFib who are prescribed oral anticoagulants remain largely unknown,” the authors wrote. “Most prior investigations are small and report that the outcome is rare.”
The researchers hypothesized that the incidence rate of traumatic intracranial bleeding would be higher than previously reported in clinical trials and that selected known risk factors for falls and bleeding would independently predict this event.
The study team focused on 31,951 U.S. veterans with AFib, 75 years or older, who were new referrals to VA anticoagulation clinics between 2002 and 2012.
With a mean patient age of 81.1 and 98.1% of the participants being male, comorbidities were common, including hypertension (82.5%), coronary artery disease (42.6%) and diabetes mellitus (33.8%), according to the report. During the study period, the incidence rate of hospitalization for traumatic intracranial bleeding was 4.80 per 1,000 person-years, according to the results.
The incidence rates of hospitalization for any intracranial bleeding and ischemic stroke were 14.58 and 13.44, respectively. Study authors noted that more than half (57.2%) of the intracranial bleeding events were nontraumatic. In addition, among the 1,317 patients who experienced any intracranial bleeding event, nearly one-third (30.9%), had more than one episode.
“As expected, this rate was considerably higher than that in previous clinical trials,” the study authors said about the intracranial bleeding rate, adding that it was in line with some smaller studies.
“Nearly one-third of patients experienced more than one episode of traumatic intracranial bleeding,” Dodson pointed out in an interview published by the National Institutes of Health. Yet, many patients “also still experienced strokes during this time period.”
AFibter adjusting for potential confounders, the significant predictors for traumatic intracranial bleeding were adjudged to be:
- dementia (hazard ratio [HR], 1.76;
- anemia (HR, 1.23);
- depression (HR, 1.30);
- anticonvulsant use (HR, 1.35); and
- labile international normalized ratio (HR, 1.33).
“Among patients 75 years or older with atrial fibrillation initiating warfarin therapy, the risk factors for traumatic intracranial bleeding are unique from those for ischemic stroke,” the study concluded. “The high overall rate of intracranial bleeding in our sample supports the need to more systematically evaluate the benefits and harms of warfarin therapy in older adults.”
In a presentation late last year at the American Heart Association Scientific Sessions in Orlando, Dodson and colleagues reported results from related research, noting that over a median follow-up period of 2.62 years, 22.8% of the VA study group who initiated warfarin for AFib were hospitalized for bleeding. With 12,004 total bleeding events, 980 (13.4%) patients experienced multiple events.2
The presenters reported that the most-common bleeding sources (first event) were:
- gastrointestinal (50.8%),
- genitourinary (21.6%), and
- intracranial (9.4%)
“AFibter initiating warfarin, over one in five older veterans are hospitalized for bleeding, most commonly from a gastrointestinal source,” the authors said. “Comorbidity burden and labile INR place these patients at increased risk.”
In the JAMA Cardiology article, the authors noted that they were unable to generate a clinical prevention tool to evaluate risk but “still believe that the individual factors we identified may potentially be used in patient-centered discussions about the benefits and harms of warfarin therapy in older adults.”
Researchers also pointed out that their study period “predated the common use of direct oral anticoagulants. These medications are increasingly used for stroke prevention in AFib and may have a different risk-benefit profile from that of warfarin in older adults. For example, the reliable effect of these medications, taken regularly, would obviate the labile INR variable, which we found to be significantly associated with bleeding risk. Therefore, we believe that the comparative risk of direct oral anticoagulants vs. warfarin, in the context of traumatic intracranial bleeding among older adults in clinical practice, warrants further investigation in future observational studies.”
The study was touted as “the largest investigation to date focused on traumatic intracranial bleeding among older adults,” 75 or older who initiated warfarin therapy for AFib.
“These findings highlight the important balance between the benefits and risks of warfarin therapy in elderly patients with a-fib, and the need for a personalized approach,” Dodson said.
1 Dodson JA, Petrone A, Gagnon DR, Tinetti ME, Krumholz HM, Gaziano JM. Incidence and Determinants of Traumatic Intracranial Bleeding Among Older Veterans Receiving Warfarin for Atrial Fibrillation. JAMA Cardiol. Published online March 09, 2016. doi:10.1001/jamacardio.2015.0345.
2 Dodson JA, Petrone A, Gagnon DR, Tinetti ME, Krumholz HM, Gaziano JM. Abstract 17598: More Than One in Five Older Veterans are Hospitalized for Bleeding Following Initiation of Warfarin for Atrial Fibrillation. Circulation. 2015;132:Suppl 3 A17598.