Apixaban Has Benefits Over Other DOACs in Frail Adults With Atrial Fibrillation

By Megan Brooks

July 22, 2021

NEW YORK (Reuters Health) - For frail older adults with atrial fibrillation (AF), apixaban has benefits over other direct oral anticoagulants (DOACs) and warfarin, a new analysis suggests.

Examining outcomes with different DOACs (versus warfarin) by frailty levels, researchers founds apixaban was associated with lower rates of adverse clinical events than warfarin across all frailty levels (non-frail, pre-frail, and frail).

Dabigatran and rivaroxaban (compared with warfarin) were associated with lower adverse events only among non-frail adults.

"These findings suggest use of apixaban for older adults with frailty," Dr. Dae Hyun Kim of Brigham and Women's Hospital and Harvard Medical School, in Boston, told Reuters Health by email.

"Frailty can predict adverse health outcomes after medical treatments (drug adverse events or complications after surgery) but a formal frailty assessment is rarely done before prescribing an anticoagulant. Physicians consider a patient's risk of falling and may use an 'eyeball' test, which is poorly standardized," Dr. Kim explained.

"The hesitancy to measure frailty is often attributed to lack of time and lack of guidance on what to do with frailty information. Because clinical trials exclude frail patients and do not measure frailty, there is little information on how to optimize prescribing for frail patients and for non-frail patients," Dr. Kim noted.

"Our study is the first attempt to fill this gap by using a claims-based frailty index we developed to enable measurement of frailty levels on a population scale when in-person assessment is not available or infeasible," Dr. Kim explained.

The findings are based on a propensity-score-matched analysis of hundreds of thousands of Medicare beneficiaries with AF who started warfarin or a DOAC (dabigatran, rivaroxaban, or apixaban) between 2010 and 2017.

Apixaban was associated with a significant 32% reduction in the risk of the composite outcome of death, ischemic stroke or major bleeding, compared with warfarin (60.1 vs. 92.3 events per 1,000 person-years) in the overall population and consistent reductions of 27% to 39% across frailty levels.

Compared with warfarin, dabigatran and rivaroxaban were not associated with a lower risk of the composite outcome in the overall population, the researchers report in Annals of Internal Medicine; however, there was a 12% to 19% reduction in risk in non-frail patients, with little or no reduction in prefrail and frail adults.

The beneficial association for apixaban versus warfarin in frail patients appeared to be mainly driven by a large reduction in major bleeding.

"Because older adults with frailty are predisposed to declines in renal function, higher renal clearance of dabigatran (80% to 85%) and rivaroxaban (66%) versus apixaban (27%) can result in higher plasma drug concentrations, thereby increasing bleeding risk," the authors point out.

They caution that due to several limitations of the analysis, the quality of evidence from this observational study can be rated "moderate" for the apixaban results and "low" for the dabigatran and rivaroxaban results.

Despite this, the results could help guide the choice of a specific DOAC versus warfarin for older adults with AF, they add.

Primary funding for the study was provided by the National Institute on Aging.

SOURCE: https://bit.ly/3eBWMQB Annals of Internal Medicine, online July 19, 2021.

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