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Real world effectiveness of warfarin among ischemic stroke patients with atrial fibrillation: observational analysis from Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study

BMJ 2015; 351 doi: (Published 31 July 2015) Cite this as: BMJ 2015;351:h3786
  1. Ying Xian, assistant professor of medicine1,
  2. Jingjing Wu, statistician1,
  3. Emily C O’Brien, medical instructor1,
  4. Gregg C Fonarow, professor of medicine2,
  5. DaiWai M Olson, associate professor of neurology and neurotherapeutics, neurological surgery3,
  6. Lee H Schwamm, professor of neurology4,
  7. Deepak L Bhatt, professor of medicine5,
  8. Eric E Smith, associate professor of neurology6,
  9. Robert E Suter, professor of emergency medicine7,
  10. Deidre Hannah, patient co-investigator,
  11. Brianna Lindholm, patient co-investigator,
  12. Lesley Maisch, patient co-investigator,
  13. Melissa A Greiner, statistician1,
  14. Barbara L Lytle, project leader1,
  15. Michael J Pencina, professor of biostatistics and bioinformatics1,
  16. Eric D Peterson, distinguished professor of medicine1,
  17. Adrian F Hernandez, associate professor of medicine1
  1. 1Duke Clinical Research Institute, 2400 Pratt Street, Durham, NC, USA
  2. 2Division of Cardiology, University of California, Los Angeles, CA, USA
  3. 3Department of Neurology and Neurotherapeutics, Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
  4. 4Stroke Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
  5. 5Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA, USA
  6. 6Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
  7. 7The American Heart Association and University of Texas Southwestern, Dallas, TX, USA
  1. Correspondence to: Y Xian ying.xian{at}
  • Accepted 21 June 2015


Objective To examine the association between warfarin treatment and longitudinal outcomes after ischemic stroke in patients with atrial fibrillation in community practice.

Design Observational study.

Setting Hospitals (n=1487) participating in the Get With The Guidelines (GWTG)-Stroke program in the United States, from 2009 to 2011.

Participants 12 552 warfarin naive atrial fibrillation patients admitted to hospital for ischemic stroke and treated with warfarin compared with no oral anticoagulant at discharge, linked to Medicare claims for longitudinal outcomes.

Main outcome measures Major adverse cardiovascular events (MACE) and home time, a patient centered outcomes measure defined as the total number of days free from institutional care after discharge. A propensity score inverse probability weighting method was used to account for all differences in observed characteristics between treatment groups.

Results Among 12 552 survivors of stroke, 11 039 (88%) were treated with warfarin at discharge. Warfarin treated patients were slightly younger and less likely to have a history of previous stroke or coronary artery disease but had similar severity of stroke as measured by the National Institutes of Health Stroke Scale. Relative to those not treated, patients treated with warfarin had more days at home (as opposed to institutional care) during the two years after discharge (adjusted home time difference 47.6 days, 99% confidence interval 26.9 to 68.2). Patients discharged on warfarin treatment also had a reduced risk of MACE (adjusted hazard ratio 0.87, 99% confidence interval 0.78 to 0.98), all cause mortality (0.72, 0.63 to 0.84), and recurrent ischemic stroke (0.63, 0.48 to 0.83). These differences were consistent among clinically relevant subgroups by age, sex, stroke severity, and history of previous coronary artery disease and stroke.

Conclusions Among ischemic stroke patients with atrial fibrillation, warfarin treatment was associated with improved long term clinical outcomes and more days at home.

Clinical trial registration Clinical trials NCT02146274.


  • We thank Erin Hanley, Duke Clinical Research Institute, for editorial assistance. She did not receive compensation for her assistance apart from her employment at the institution where this study was conducted.

  • Contributors: All authors were involved in the study design, data analysis, and revision of the manuscript. All authors read and approved the final manuscript. YX is the guarantor.

  • Funding: This work was supported by an award (CE-1304) from the Patient-Centered Outcomes Research Institute (PCORI). The funders of the study had no role in the study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit the article for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: support by PCORI for the submitted work. YX reports research funding to Duke Clinical Research Institute from the American Heart Association, Daiichi Sankyo, Janssen Pharmaceuticals, and Genentech. GCF serves as a member of the Get With The Guidelines (GWTG) Steering Committee; receives research support from the National Institutes of Health and PCORI; and is an employee of the University of California, which holds a patent on retriever devices for stroke. LHS is the principal investigator of an investigator initiated study of extended window intravenous thrombolysis funded by the National Institutes of Neurological Disorders and Stroke (, for which Genentech provides alteplase free of charge to Massachusetts General Hospital as well as supplemental per patient payments to participating sites; he also serves as chair of the American Heart Association/American Stroke Association GWTG Stroke Clinical Work Group, as a stroke systems consultant to the Massachusetts Department of Public Health, and as a scientific consultant regarding trial design and conduct to Lundbeck (international steering committee, DIAS3, 4 trial) and Penumbra (data and safety monitoring committee, Separator 3D trial). DLB serves on advisory boards for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; on the Board of Directors of Boston VA Research Institute and Society of Cardiovascular Patient Care; is chair of the American Heart Association GWTG Steering Committee; serves on data monitoring committees for Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; has received honorariums from the American College of Cardiology (senior associate editor, clinical trials and news,, Belvoir Publications (editor in chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (associate editor; section editor, pharmacology), Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, cardiology today’s intervention), WebMD (CME steering committees); is deputy editor of Clinical Cardiology; has received research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi Aventis, and The Medicines Company; and has conducted unfunded research for FlowCo, PLx Pharma, and Takeda. EES serves as a member of the GWTG Steering Committee. RES is employed as the vice president of quality and HIT by the American Heart Association/American Stroke Association, which receives grant funding from multiple pharmaceutical and other sources. EDP has received research grants from Lilly, Johnson & Johnson, Bristol-Myers Squibb, Sanofi-Aventis, and Merck-Schering Plough partnership; and serves as principal investigator of the data analytic center for the American Heart Association/American Stroke Association’s GWTG program. AFH has received research grants from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, and Portola Pharmaceuticals and honorariums from Amgen, GlaxoSmithKline, Janssen, and Novartis.

  • Ethical approval: The institutional review board of the Duke University Health System approved this study.

  • Data sharing: No additional data available.

  • Transparency declaration: The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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