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 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.






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Publication Info

Xian, Ying, Haolin Xu, Emily C O'Brien, Shreyansh Shah, Laine Thomas, Michael J Pencina, Gregg C Fonarow, DaiWai M Olson, et al. (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. JAMA neurology. 10.1001/jamaneurol.2019.2099 Retrieved from

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Ying Xian

Adjunct Associate Professor in the Department of Neurology

Haolin Xu

Biostatistician, Senior

Emily O'Brien

Associate Professor in Population Health Sciences

Dr. Emily O’Brien is Associate Professor in Population Health Sciences, Associate Professor in Neurology, Core Faculty Member at Duke-Margolis Center for Health Policy,  and Co-Director of Population Health Sciences at the Duke Clinical Research Institute. Her research focuses on comparative effectiveness, patient-centered outcomes, and pragmatic health systems research in cardiovascular and pulmonary disease. Her areas of expertise include: Epidemiology, Pragmatic Clinical Trials, and Clinical Decision Sciences. Dr. O’Brien received her PhD in Epidemiology from the University of North Carolina in Chapel Hill. As principal investigator for projects funded by the FDA, NIH, and PCORI, she has extensive experience working with diverse data sources including registries, epidemiologic cohorts, electronic health records, and administrative claims data. Dr. O’Brien teaches Analytic Methods in the Department of Population Health Sciences PhD program and has co-authored over 160 manuscripts in peer-reviewed journals on topics ranging from epidemiologic methods, comparative effectiveness, and pragmatic clinical trials. She is an associate editor for Circulation: Cardiovascular Quality and Outcomes, Chair of the AHA QCOR Scientific & Clinical Education Lifelong Learning Committee, social media editor for the Journal of the American Heart Association, and a fellow of the American Heart Association.


Shreyansh Shah

Assistant Professor of Neurology

Laine Elliott Thomas

Professor of Biostatistics & Bioinformatics

Laine Thomas, PhD, joined the Department of Biostatistics and Bioinformatics and DCRI in 2009.  She serves as Associate Chair for Equity, Diversity and Inclusion within the Department of Biostatistics and Bioinformatics and Deputy Director of Data Science and Biostatistics at the Duke Clinical Research Institute.  She is a leader in study design and development of methods for observational and pragmatic studies, with over 240 peer reviewed clinical and methodological publications arising from scientific collaboration in the therapeutic areas of cardiovascular disease, diabetes, uterine fibroids and SARS-CoV-2 virus. She led the statistical teams on the HERO COVID-19, ORBIT-AF I & II, ACTION-CMS, CHAMP-HF, and COMPARE-UF clinical registries and secondary analyses of the NAVIGATOR and ARISTOTLE clinical trials. She has served as a primary investigator and co-investigator on numerous methodological studies with funding from NIH, AHRQ, PCORI and Burroughs Wellcome Fund, addressing observational treatment comparisons, time-varying treatments, heterogeneity of treatment effects, and randomized trials augmented by synthetic controls from real world data.      


Michael J Pencina

Professor of Biostatistics & Bioinformatics

Michael J. Pencina, PhD
Chief Data Scientist, Duke Health
Vice Dean for Data Science
Director, Duke AI Health
Professor, Biostatistics & Bioinformatics
Duke University School of Medicine

Michael J. Pencina, PhD, is Duke Health's chief data scientist and serves as vice dean for data science, director of Duke AI Health, and professor of biostatistics and bioinformatics at the Duke University School of Medicine. His work bridges the fields of data science, health care, and AI, contributing to Duke’s national leadership in trustworthy health AI.

Dr. Pencina partners with key leaders to develop data science strategies for Duke Health that span and connect academic research and clinical care. As vice dean for data science, he develops and implements quantitative science strategies to support the School of Medicine’s missions in education and training, laboratory and clinical science, and data science.

He co-founded and co-leads the national Coalition for Health AI (CHAI), a multi-stakeholder effort whose mission is to increase trustworthiness of AI by developing guidelines to drive high-quality health care through the adoption of credible, fair, and transparent health AI systems. He also spearheaded the establishment and co-chairs Duke Health’s Algorithm-Based Clinical Decision Support (ABCDS) Oversight Committee and serves as co-director of Duke’s Collaborative to Advance Clinical Health Equity (CACHE).

Dr. Pencina is an internationally recognized authority in the evaluation of AI algorithms. Guideline groups rely on his work to advance best practices for the application of clinical decision support tools in health delivery. He interacts frequently with investigators from academic and industry institutions as well as government officials. Since 2014, he has been acknowledged annually by Thomson Reuters/Clarivate Analytics as one of the world’s "highly cited researchers" in clinical medicine and social sciences, with over 400 publications cited over 100,000 times. He serves as a deputy editor for statistics at JAMA-Cardiology.

Dr. Pencina joined the Duke University faculty in 2013, and served as director of biostatistics for the Duke Clinical Research Institute until 2018. Previously, he was an associate professor in the Department of Biostatistics at Boston University and the Framingham Heart Study, and director of statistical consulting at the Harvard Clinical Research Institute. He received his PhD in Mathematics and Statistics from Boston University in 2003 and holds master’s degrees from the University of Warsaw in actuarial mathematics and business culture.


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Adrian Felipe Hernandez

Duke Health Cardiology Professor

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