Nearly a quarter of older patients with atrial fibrillation receive inappropriately dosed direct-acting oral anticoagulants (DOACs), according to an analysis of the ongoing SAGE-AF (Systematic Assessment of Geriatric Elements in Atrial Fibrillation) study.
The research, penned by Saket Sanghai, MBBS, and colleagues and published in the Journal of the American Heart Association on March 9, involved developing an algorithm to analyze DOAC dose appropriateness for AFib patients aged 65 and up. Sanghai and co-authors said that DOACs like dabigatran, apixaban, rivaroxaban and edoxaban are all approved by the FDA to prevent thromboembolic events in patients with nonvalvular AFib, but recent studies suggest that between 10% and 15% of patients treated with DOACs were receiving potentially inappropriate doses.
“Inappropriate dosing has potential clinical consequences, including thromboembolism, bleeding and death,” Sanghai, of the Knight Cardiovascular Institute at Oregon Health & Science University, et al. wrote in JAHA. “However, the reasons for choosing an off-label dosing regimen in such patients are not clear based on previous data.”
The team performed geriatric assessments for patients in the SAGE-AF study, accounting for any frailty, cognitive impairment, sensory impairment, social isolation or depression. Patients included in the researchers’ analysis were all older, had a CHA2DS2VASc score of 2 or greater and exhibited no anticoagulant contraindications.
Sanghai et al.’s dose-appropriateness algorithm took into consideration drug-drug interactions, patient age, renal function and body weight. They found that of 1,064 patients prescribed anticoagulants, 460 received a DOAC, and 23% of that subset received an inappropriate DOAC dose. The majority of people who were dosed inappropriately were underdosed (78% of patients), while the rest were overdosed (22% of patients).
The team said that among participants who received an inappropriate DOAC dose, 12 patients—11% of the pool—were identified using the drug-drug interactions criteria. If it weren’t for the criteria, Sanghai and colleagues said, those people would have been misclassified.
“Drug-drug interactions were common,” the authors wrote. “Factors that influence prescription of guideline-nonadherent doses may be perception of higher bleeding risk or presence of renal failure in addition to lack of familiarity with dosing guidelines.”
They said that in multivariable regression analyses, older age, higher CHA2DS2VASc score and history of renal failure were linked to inappropriate DOAC dosing. Geriatric conditions didn’t seem to be related to the issue.
“Further research is needed to determine the association between dosing and clinical outcomes and strategies to prevent unintentional inappropriate dosing by prescribers,” Sanghai and colleagues said.