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

Abstract

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.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (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 (clinicaltrials.gov/show/NCT01282242), 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, acc.org), 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.

© Xian et al 2015.

Figures

Fig 1 Study population from initial cohort, through exclusions, to final population. CMS=Centers for Medicare and Medicaid Services; GWTG-Stroke=Get With The Guidelines-Stroke; NIHSS=National Institutes of Health Stroke Scale

Fig 2 Cumulative incidences for major adverse cardiovascular event during two year follow-up for patients receiving warfarin versus no oral anticoagulant

Fig 3 Major adverse cardiovascular event (MACE) and home time according to warfarin treatment at discharge, overall and in clinically relevant subgroups. CAD=coronary artery disease; MI=myocardial infarction; NIHSS=National Institutes of Health Stroke Scale; TIA=transient ischemic attack