Physicians' Academy for Cardiovascular Education

Comparison of two DOACs in AF patients

Association of rivaroxaban vs apixaban with major ischemic or hemorrhagic events in patients with atrial fibrillation

Literature - Ray WA, Chung CP, Stein CM, et al. - JAMA. 2021 Dec 21;326(23):2395-2404. Doi: 10.1001/jama.2021.21222

Introduction and methods


Patients with AF are preferably treated with a DOAC, such as apixaban and rivaroxaban, to prevent ischemic stroke [1]. Apixaban and rivaroxaban are both reversible inhibitors of activated factor X and have similar half-lives [2]. Because apixaban is taken twice daily, while a single dose is sufficient for rivaroxaban, the concentration of rivaroxaban varies considerably more throughout the day [2,3]. This raises the question of how the effectiveness and safety of both anticoagulants compare.

Aim of the study

The aim of this study to compare the effectiveness and safety of apixaban and rivaroxaban in patients with AF.


The researchers conducted a retrospective cohort study based on data from the U.S. health insurance company Medicare. Patients aged 65 years or older who had been diagnosed with AF or atrial flutter in the past 90 days and initiated treatment with apixaban (2.5 or 5 mg twice daily; n=353,879) or rivaroxaban (15 or 20 mg once daily; n=227,572) during the period January 1, 2013-November 30, 2018, were included. Patients with terminal illness, mitral valve stenosis, severe chronic kidney disease, mechanical heart valve, or a condition causing a reversible AF were excluded from participation. Also, long-term care residents and patients who had been treated with a DOAC in the past year or who had been hospitalized for stroke or bleeding in the past 30 days were excluded. The follow-up period was 4 years, beginning the day after filling the initial DOAC prescription.


The primary outcome was a composite of major ischemic events (ischemic stroke, systemic embolism) and major hemorrhagic events (intracerebral hemorrhage, other intracranial hemorrhage, fatal extracranial hemorrhage). Secondary outcomes were nonfatal extracranial bleeding and total mortality (death from an ischemic or hemorrhagic event, death from any other cause). Data on the outcome measures were collected from hospital principal discharge codes.

The analysis adjusted for covariates with stabilized inverse probability of treatment weights calculated from the propensity score. The propensity score was estimated with logistic regression that was stratified by anticoagulant dose.

Main results

Primary outcome

Secondary outcomes


In patients aged 65 years or older with AF, treatment with rivaroxaban more often resulted in major ischemic or hemorrhagic events, compared with apixaban.


Show references

Find this article online at JAMA.

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