Treatment with direct oral anticoagulants (DOACs) at discharge following acute ischemic stroke among patients with atrial fibrillation is an effective and safe treatment option, with a superior risk-benefit ratio compared with warfarin, according to study results published in JAMA Neurology.

Clinical guidelines recommend DOACs over warfarin for stroke prevention in patients with atrial fibrillation. Therefore, DOACs have increasingly been used over warfarin and are recommended as first-line anticoagulant therapy. However, because real-world evidence is limited and does not include high-risk populations, the goal of this study was to assess the clinical effectiveness of DOACs (dabigatran, rivaroxaban, or apixaban) vs warfarin in older survivors of acute ischemic stroke with atrial fibrillation who were prescribed oral anticoagulants at hospital discharge.

Primary outcomes included home time, defined as the total number of days free from death and institutional care after discharge, and major adverse cardiovascular events (MACE). A propensity score-overlap weighting approach was used to control for potential selection bias.

This retrospective study included 11,662 patients aged 65 years or older (median age 80 years) with a medical history of atrial fibrillation or flutter admitted to Get With The Guidelines Stroke associated hospitals and discharged alive between October 2011 and December 2014 after an acute ischemic stroke. All participants were not treated previously with anticoagulants. Of the patients included, 7621 (65.3%) were prescribed warfarin and 4041 patients (34.7%) were prescribed DOACs: 1239 were prescribed dabigatran, 1842 rivaroxaban, and 960 apixaban.

During the first year after discharge, mean home time was 287.2±114.7 days for patients receiving DOACs at discharge compared with 263.0±127.3 days for those receiving warfarin.

A MACE was documented in 1930 patients (34.0% per year) given DOACs compared with 4476 patients (40.4% per year) given warfarin. After propensity score-overlap weighting, treatment with DOACs at discharge was associated with more days alive and out of the hospital or a skilled nursing facility (adjusted home time difference, 15.6 days), and with lower risk for MACEs (adjusted hazard ratio [aHR] 0.89 [99% CI, 0.83-0.96]) compared with warfarin treatment.

Treatment with DOACs at discharge was associated with a lower risk for all-cause mortality compared with warfarin (15.8% per year vs 19.6% per year; aHR 0.88; 95% CI, 0.82-0.95; P <.001), all-cause readmissions (53.1% per year vs 62.4% per year; aHR 0.93; 95% CI, 0.88-0.97; P =.003), cardiovascular readmissions (22.3% per year vs 25.0% per year; aHR 0.92; 95% CI, 0.86-0.99; P =.02), hemorrhagic stroke (0.8% per year vs 1.0% per year; aHR 0.69; 95% CI, 0.50-0.95; P =.02), and hospitalizations with bleeding (11.4% per year vs 13.4% per year; aHR 0.89; 95% CI, 0.81-0.97; P =.009). However, an increased risk for gastrointestinal bleeding (5.4% per year vs 5.1% per year; aHR 1.14; 95% CI, 1.01-1.30; P =.03) was found in those treated with DOACs.

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The researchers acknowledged several study limitations, including the retrospective design, assessment of long-term outcomes of secondary prevention and not primary prevention as the study was limited to patients who experienced stroke, and selection bias resulting from the exclusion criteria used.

“These findings provide empirical support for current guideline recommendations and confirm the improved risk-benefit ratio in DOAC vs warfarin for secondary prevention in patients with [atrial fibrillation],” concluded the researchers.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Xian Y, Xu H, O’Brien EC, et al. Clinical effectiveness of direct oral anticoagulants vs warfarin in older patients with atrial fibrillation and ischemic stroke: findings from the patient-centered research into outcomes stroke patients prefer and effectiveness research (PROSPER) study [Published online July 22, 2019]. JAMA Neurol. doi:10.1001/jamaneurol.2019.2099