Risk Factors for Intracranial Bleeding in Older Patients with Atrial Fibrillation Who Are on Anticoagulants

A large retrospective analysis concludes that an unexpectedly high rate of serious bleeds may contraindicate warfarin use in some groups of older patients with atrial fibrillation (AFib).

Investigators examined medical records from 31,951 veterans aged 75 years and older who began using the anticoagulant between January 1, 2002, and December 31, 2012. The mean patient age was 81.1 years at baseline (standard deviation: ± 4.1 years), 98.1% of the patients were male and the mean follow-up time was 2.97 years. Common comorbidities included hypertension (82.5%), coronary artery disease (42.6%), and diabetes mellitus (33.8%).

The overall rate of hospitalization for ischemic stroke was 13.44 per 1,000 person-years, while the overall rate of hospitalization for any type of intracranial bleeding was 14.58 per 1,000 person-years and the overall rate of hospitalization for traumatic intracranial bleeding was 4.80 per 1,000 person years.

Certain patient groups, however, were significantly more likely than average to suffer from those traumatic bleeds. After adjusting for potential confounders, the investigators found 5 significant predictors of traumatic intracranial bleeding: dementia (hazard ratio [HR], 1.76; 95% CI, 1.26-2.46), anemia (HR, 1.23; 95% CI, 1.00-1.52), depression (HR, 1.30; 95% CI, 1.05-1.61), anticonvulsant use (HR, 1.35; 95% CI, 1.04-1.75), and labile international normalized ratio (HR, 1.33; 95% CI, 1.04-1.72).

“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 authors wrote in JAMA Cardiology. “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.”

The benefits of anticoagulation in elderly AFib patients are well established. Existing research indicates that effective anticoagulation regimens reduce the risk of thromboembolic stroke in older AFib patients by nearly 67%.

The harms of anticoagulation are less clear. Most prior investigations followed small numbers of patients for short periods of time and found adverse outcomes to be rare, wrote the authors of the new study, who hoped their large sample size and long study duration would identify not only overall harms but also individual risk factors.

The primary direct cause of intracranial bleeding in elderly patients is a serious fall, so the investigators were not surprised to see that many of the risk factors they identified have already been linked to increased fall risk.

“Dementia is known from prior studies to increase fall risk considerably. In a cohort of 2015 older adult nursing home residents, the relative risk for dementia and falls was 1.93 after adjusting for other characteristics,” the study authors wrote. “Other factors, such as difficulty following medication instructions or dietary noncompliance, may also have a role through excessive anticoagulation or increased international normalized ratio variability. In this context, we believe that our findings further support the perceived increased risk of warfarin therapy in patients with dementia and can potentially be used in individualized discussions with patients and caregivers when considering the risk-benefit trade-off.”

The investigators acknowledged that the strength of the association between intracranial bleeding and the other risk factors they identified was not so strong as the association with dementia. However, they noted, all the other risk factors have been shown in prior studies to be associated with either falls or bleeding.