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Original Investigation
July 22, 2019

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

Author Affiliations
  • 1Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
  • 2Department of Neurology, Duke University Medical Center, Durham, North Carolina
  • 3Division of Cardiology, University of California, Los Angeles
  • 4University of Texas Southwestern, Dallas
  • 5Harvard Medical School, Massachusetts General Hospital, Boston
  • 6Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts
  • 7Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
  • 8Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research Study, Durham, North Carolina
JAMA Neurol. 2019;76(10):1192-1202. doi:10.1001/jamaneurol.2019.2099
Key Points

Question  Is direct oral anticoagulant a better option than warfarin for secondary prevention in older survivors of ischemic stroke who have atrial fibrillation?

Findings  In this observational study of 11 662 patients with atrial fibrillation who had had an ischemic stroke and were anticoagulation naive, patients discharged while receiving direct oral anticoagulants had more days at home postdischarge and were less likely to experience major adverse cardiovascular events, all-cause mortality, all-cause readmissions, cardiovascular readmissions, or hemorrhagic strokes, despite a small but significant increase in gastrointestinal bleeding.

Meaning  Direct oral anticoagulants appear to be an effective and safe treatment option compared with warfarin for patients with atrial fibrillation who have ischemic stroke.


Importance  Current guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention in patients with atrial fibrillation (AF) who are at high risk. Despite demonstrated efficacy in clinical trials, real-world data of DOACs vs warfarin for secondary prevention in patients with ischemic stroke are largely based on administrative claims or have not focused on patient-centered outcomes.

Objective  To examine the clinical effectiveness of DOACs (dabigatran, rivaroxaban, or apixaban) vs warfarin after ischemic stroke in patients with AF.

Design, Setting, and Participants  This cohort study included patients who were 65 years or older, had AF, were anticoagulation naive, and were discharged from 1041 Get With The Guidelines–Stroke–associated hospitals for acute ischemic stroke between October 2011 and December 2014. Data were linked to Medicare claims for long-term outcomes (up to December 2015). Analyses were completed in July 2018.

Exposures  DOACs vs warfarin prescription at discharge.

Main Outcomes and Measures  The primary outcomes were home time, a patient-centered measure defined as the total number of days free from death and institutional care after discharge, and major adverse cardiovascular events. A propensity score–overlap weighting method was used to account for differences in observed characteristics between groups.

Results  Of 11 662 survivors of acute ischemic stroke (median [interquartile range] age, 80 [74-86] years), 4041 (34.7%) were discharged with DOACs and 7621 with warfarin. Except for National Institutes of Health Stroke Scale scores (median [interquartile range], 4 [1-9] vs 5 [2-11]), baseline characteristics were similar between groups. Patients discharged with DOACs (vs warfarin) had more days at home (mean [SD], 287.2 [114.7] vs 263.0 [127.3] days; adjusted difference, 15.6 [99% CI, 9.0-22.1] days) during the first year postdischarge and were less likely to experience major adverse cardiovascular events (adjusted hazard ratio [aHR], 0.89 [99% CI, 0.83-0.96]). Also, in patients receiving DOACs, there were fewer deaths (aHR, 0.88 [95% CI, 0.82-0.95]; P < .001), all-cause readmissions (aHR, 0.93 [95% CI, 0.88-0.97]; P = .003), cardiovascular readmissions (aHR, 0.92 [95% CI, 0.86-0.99]; P = .02), hemorrhagic strokes (aHR, 0.69 [95% CI, 0.50-0.95]; P = .02), and hospitalizations with bleeding (aHR, 0.89 [95% CI, 0.81-0.97]; P = .009) but a higher risk of gastrointestinal bleeding (aHR, 1.14 [95% CI, 1.01-1.30]; P = .03).

Conclusions and Relevance  In patients with acute ischemic stroke and AF, DOAC use at discharge was associated with better long-term outcomes relative to warfarin.