Warfarin increases intracranial bleeding risk in older adults with AF

Veterans with atrial fibrillation aged at least 75 years assigned warfarin had higher rates of intracranial bleeding than seen in clinical trial populations, according to findings published in JAMA Cardiology.

Researchers conducted a retrospective cohort study of 31,951 veterans aged 75 years or older (mean age, 81.1 years; 98.1% men; 82.5% with hypertension; 42.6% with CAD; 33.8% with diabetes) with AF who were newly referred for warfarin therapy to VA anticoagulation clinics between 2002 and 2012. The findings were initially presented at the American Heart Association Scientific Sessions in November.

The primary outcome was hospitalization for traumatic intracranial bleeding, as verified by VA and Medicare claims databases. Secondary outcomes included hospitalization for any intracranial bleeding or ischemic stroke. Median follow-up was 2.97 years.

John A. Dodson, MD, MPH, and colleagues determined that the incidence rate for hospitalization due to traumatic intracranial bleeding was 4.8/1,000 person-years.

John A. Dodson

They also found that the incidence rate of hospitalization for any intracranial bleeding was 14.58/1,000 person-years; for ischemic stroke, the rate was 13.44/1,000 person-years.

Bleeding predictors

When Dodson, assistant professor in the division of cardiology of the department of medicine and the department of population health at New York University School of Medicine, and colleagues performed unadjusted analyses, they found the following characteristics were predictors of hospitalization for traumatic intracranial bleeding:

dementia;
fall within 1 year prior;
anemia;
depression;
abnormal renal or liver function;
use of an anticonvulsant;
labile INR; and
use of antihypertensive medication.

When they adjusted for confounders, the following variables remained significant predictors: dementia (HR = 1.76; 95% CI, 1.26-2.46), anemia (HR = 1.23; 95% CI, 1-1.52), depression (HR = 1.3; 95% CI, 1.05-1.61), use of an anticonvulsant (HR = 1.35; 95% CI, 1.04-1.75) and labile INR (HR = 1.33; 95% CI, 1.04-1.72).

No easy answer

“For the clinician in practice, our findings indicate that there is a real risk for traumatic intracranial bleeding, as well as nontraumatic intracranial bleeding, with warfarin, although there is also a considerable risk for ischemic stroke, even on therapy,” Dodson told Cardiology Today. “So unfortunately, there is no easy answer. But if I had a patient in the office with dementia, I may think twice about recommending warfarin therapy.”

Dodson also said that comparative studies between warfarin, direct oral anticoagulants and left atrial appendage exclusion devices are needed, and that because the population in the present study was almost exclusively men aged 75 years and older, “it will be important to replicate our findings in other populations to see if they apply to women.” – by Erik Swain

References:

Dodson JA, et al. Abstract 2068. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.

Dodson JA, et al. JAMA Cardiol. 2016;doi:10.1001/jamacardio.2015.0345.

For more information:

John A. Dodson, MD, MPH, can be reached at Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, 227 E 30th St, Translational Research Bldg Room 851, New York, NY 10706; email: john.dodson@nyumc.org.

Disclosure: One researcher reports receiving research grants from Johnson & Johnson and Medtronic and chairing a scientific advisory board for UnitedHealthcare.