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Very elderly people with nonvalvular atrial fibrillation (Afib) got the same stroke prevention benefits from edoxaban (Savaysa) and apixaban (Eliquis), though one drug was associated with more major bleeding in a comparative effectiveness study based on a large population-based cohort.

The two direct oral anticoagulants (DOACs) produced similar primary effectiveness in terms of ischemic stroke, transient ischemic attack, and systemic embolism (weighted incidence rate 20.38 vs 19.22 events per 1,000 person-years; adjusted HR 1.06, 95% CI 0.89-1.26), reported Christel Renoux, MD, PhD, of Jewish General Hospital in Montreal, Quebec, and colleagues.

However, major bleeding rates were lower for apixaban, driven by differences in gastrointestinal bleeding and other nonspecified bleeding (45.57 vs 31.21 per 1,000 person-years; adjusted HR 1.42, 95% CI 1.26-1.61). Both standard- and low-dose edoxaban were associated with significantly more major bleeding compared with apixaban.

"These findings may improve the management of nonvalvular [Afib] by informing physicians on the choice of anticoagulant for this vulnerable population," the investigators wrote of their observational study published in .

Despite the established importance of oral anticoagulant (OAC) therapy for people with nonvalvular Afib, the lack of head-to-head trials and scanty evidence on their effectiveness and safety in elderly people -- a population under-represented in the pivotal DOAC trials -- has made it difficult for clinicians to adopt it in clinical practice for this bleeding-prone, high-risk population, Renoux's group wrote. Although older Afib patients were increasingly willing to initiate and adhere to their prescribed OACs in recent years, they remain undertreated as a whole.

Four DOACs have been approved in the U.S.: apixaban, edoxaban, rivaroxaban (Xarelto), and dabigatran (Pradaxa).

"Existing evidence-based guidelines do not identify a preferred DOAC instead guiding clinicians to consider specific patient circumstances such as the availability of an antidote to appropriately narrow choices for patients with a high bleeding risk," according to Melina Gattellari, PhD, MPH, of Royal Prince Alfred Hospital in Camperdown, Australia, in .

The present study results "compel us to ask whether all anticoagulants are created equally. This question has yet to entice trialists but arguably should," she wrote, adding that a large trial, counting around 10,000 patients per arm, would be needed to directly compare DOACs.

Medicare records had suggested that older people with Afib, especially those with frailty, had better patient-centered outcomes taking apixaban rather than other commonly used OACs.

Here, Renoux and colleagues sought to compare apixaban with edoxaban, a relatively unpopular OAC with scant real-world evidence.

Their population-based study relied on the United Kingdom Clinical Practice Research Datalink. With this large primary care database, the investigators identified all people with incident nonvalvular Afib who were newly treated with edoxaban (n=7,251) or apixaban (n=39,991) from 2015 to 2021 when they were already 80 years or older.

Median follow-up lasted from 255 to 262 days for patients treated with edoxaban and from 317 to 322 days for patients treated with apixaban.

Outcomes were adjusted by propensity score weighting to account for baseline differences between apixaban and edoxaban users.

Secondary results include a similar risk of all-cause mortality between groups (118.43 vs 113.70 per 1,000 person-years; adjusted HR 1.04, 95% CI 0.96-1.12) but an advantage for apixaban for the composite outcome counting ischemic stroke, transient ischemic attack, systemic embolism, gastrointestinal bleeding, and intracranial hemorrhage (44.34 vs 36.12 per 1,000 person-years; adjusted HR 1.21, 95% CI 1.07-1.38).

"Similar to evidence available in younger patients, our results suggest that edoxaban and apixaban offer similar effectiveness for the prevention of ischemic stroke in patients over 80, with no modification by age, sex, frailty, CHA2DS2-VASc score, history of OAC use and dose," Renoux's team reported.

However, the observational study was subject to residual confounding, precluding any causal conclusions from being drawn between DOAC choice and outcomes in the elderly.

"Apixaban also requires twice- rather than once-daily dosing. It is conceivable that groups systematically differed in medication adherence or compliance with risk prevention advice," Gattellari cautioned.

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