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

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 11662 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.